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Trichlorfon

PubChem CID
5853
Structure
Trichlorfon_small.png
Trichlorfon_3D_Structure.png
Molecular Formula
Synonyms
  • TRICHLORFON
  • Metrifonate
  • Chlorophos
  • 52-68-6
  • Metriphonate
Molecular Weight
257.43 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-26
  • Modify:
    2025-01-18
Description
Trichlorfon is a white crystalline solid. It is a wettable powder. It can cause illness by inhalation, skin absorption and/or ingestion. It is used as a pesticide.
Trichlorfon is a phosphonic ester that is dimethyl phosphonate in which the hydrogen atom attched to the phosphorous is substituted by a 2,2,2-trichloro-1-hydroxyethyl group. It has a role as an EC 3.1.1.7 (acetylcholinesterase) inhibitor, an agrochemical, an EC 3.1.1.8 (cholinesterase) inhibitor, an anthelminthic drug and an insecticide. It is an organic phosphonate, a phosphonic ester and an organochlorine compound.
Metrifonate or trichlorfon is an irreversible organophosphate acetylcholinesterase inhibitor. It is a prodrug which is activated non-enzymatically into 2,2-dichlorovinyl dimethyl phosphate.
See also: Atropine; Trichlorfon (component of); Oxfendazole; Trichlorfon (component of); Mebendazole; Trichlorfon (component of) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Trichlorfon.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

2,2,2-trichloro-1-dimethoxyphosphorylethanol
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C4H8Cl3O4P/c1-10-12(9,11-2)3(8)4(5,6)7/h3,8H,1-2H3
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

NFACJZMKEDPNKN-UHFFFAOYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

COP(=O)(C(C(Cl)(Cl)Cl)O)OC
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C4H8Cl3O4P
Computed by PubChem 2.2 (PubChem release 2021.10.14)
C4H8Cl3O4P

2.3 Other Identifiers

2.3.1 CAS

52-68-6
56042-26-3
56042-27-4

2.3.2 Deprecated CAS

37333-09-8, 50924-44-2, 56042-25-2, 66758-31-4
37333-09-8, 56042-25-2, 66758-31-4

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 UN Number

2.3.6 ChEBI ID

2.3.7 ChEMBL ID

2.3.8 DrugBank ID

2.3.9 DSSTox Substance ID

2.3.10 HMDB ID

2.3.11 ICSC Number

2.3.12 KEGG ID

2.3.13 Metabolomics Workbench ID

2.3.14 NCI Thesaurus Code

2.3.15 Nikkaji Number

2.3.16 NSC Number

2.3.17 Wikidata

2.3.18 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Bilarcil
  • Chlorofos
  • Chlorophos
  • Dipterex
  • Dylox
  • Foschlor
  • Metrifonate
  • Metriphonate
  • Neguvon
  • Ricifon
  • Trichlorfon
  • Trichlorphon

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
257.43 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
0.5
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
255.922579 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
255.922579 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
55.8 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
12
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
183
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
1
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Trichlorfon is a white crystalline solid. It is a wettable powder. It can cause illness by inhalation, skin absorption and/or ingestion. It is used as a pesticide.
White solid; [Merck Index] White solid; Formulated as soluble powder and granular products; [Reference #2]
WHITE CRYSTALS.
White crystalline solid.

3.2.2 Color / Form

White crystals
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1784
White, crystalline solid
Larranaga, M.D., Lewis, R.J. Sr., Lewis, R.A.; Hawley's Condensed Chemical Dictionary 16th Edition. John Wiley & Sons, Inc. Hoboken, NJ 2016., p. 1364
Colorless crystals
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V30: 208 (1983)

3.2.3 Odor

Ethyl ether-like
U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.
Weak, characteristic odor
MacBean C, ed; e-Pesticide Manual. 15th ed., ver. 5.1, Alton, UK; British Crop Protection Council. Trichlorfon (52-68-6) (2008-2010)

3.2.4 Boiling Point

212 °F at 0.1 mmHg (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
BP: 100 °C at 0.1 mm Hg
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-518
212 °F at 0.1 mmHg

3.2.5 Melting Point

181 to 183 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
82.2 °C
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-518
83-84 °C
181-183 °F

3.2.6 Solubility

10 to 50 mg/mL at 70 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
In water, 1.20X10+5 mg/L at 25 °C
Wauchope RD et al; Rev Environ Contam Toxicol 123:1-36 (1991)
Soluble in benzene, ethanol; sparsely soluble in diethyl ether and petroleum ether
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 12th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2012., p. V5: 4350
Solubility: 152 g/kg in benzene; 299 g/kg in dichloromethane; 200 g/kg in isopropanol; 30 g/kg in toluene
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V5: 5131
Soluble in benzene, chloroform, ether; insoluble in oils
Larranaga, M.D., Lewis, R.J. Sr., Lewis, R.A.; Hawley's Condensed Chemical Dictionary 16th Edition. John Wiley & Sons, Inc. Hoboken, NJ 2016., p. 1364
Very soluble in methylene chloride; freely soluble in acetone, alcohol, chloroform, ether; soluble in benzene; very slightly soluble in hexane, pentane, carbon tetrachloride, diethyl ether
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1784
Solubility in water, g/100ml at 25 °C: 15.4

3.2.7 Density

1.73 at 68 °F (USCG, 1999) - Denser than water; will sink
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.
1.73 g/cu cm at 20 °C
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-518
Relative density (water = 1): 1.73
1.73

3.2.8 Vapor Pressure

7.8e-06 mmHg at 68 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
0.0000078 [mmHg]
7.8X10-6 mm Hg at 20 °C
Freed VH et al; Environ Health Perspect 20: 55-70 (1977)
Vapor pressure, Pa at 20 °C:
7.8x10-6

3.2.9 LogP

log Kow = 0.51
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 9
0.48

3.2.10 Stability / Shelf Life

Stable under recommended storage conditions.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Stable at room temperature.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V30 208 (1983)
Subject to hydrolysis and dehydrochlorination. Decomposition proceeds more rapidly with heating, and above pH 6. Rapidly converted by alkalis to dichlorvos, which is then hydrolyzed.
Tomlin CDS, ed. Trichlorfon (52-68-6). In: The e-Pesticide Manual, 13th Edition Version 3.2 (2005-06). Surrey UK, British Crop Protection Council.
Slowly decomposed in aqueous acidic solutions
Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. Old Woking, Surrey, United Kingdom: Royal Society of Chemistry/Unwin Brothers Ltd., 1983., p. A408/Oct 83

3.2.11 Decomposition

Decomposed by alkali.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1784
When heated to decomposition it emits very toxic fumes of /chloride and phosphorous oxides/.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3529

3.2.12 Corrosivity

Corrosive to metals
Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987., p. A408/Aug 87

3.2.13 Refractive Index

Index of refraction = 1.3439 at 20 °C/D
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1784

3.2.14 Collision Cross Section

148.73 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

142.65 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111
136.12 Ų [M+H]+ [CCS Type: TW]

135.96 Ų [M+H]+

148.98 Ų [M+Na]+

S61 | UJICCSLIB | Collision Cross Section (CCS) Library from UJI | DOI:10.5281/zenodo.3549476

3.2.15 Kovats Retention Index

Standard non-polar
1402 , 1431 , 1453 , 1419.2 , 1448.3
Semi-standard non-polar
1461.1 , 1427.8 , 1446

3.2.16 Other Experimental Properties

Decomposed by alkali
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1784
Subject to hydrolysis and dehydrochlorination. Decomposition proceeds more rapidly with heating and above pH 6.
MacBean C, ed; e-Pesticide Manual. 15th ed., ver. 5.1, Alton, UK; British Crop Protection Council. Trichlorfon (52-68-6) (2008-2010)

3.3 SpringerMaterials Properties

3.4 Chemical Classes

3.4.1 Drugs

3.4.1.1 Animal Drugs
Active Ingredients (Trichlorfon) -> FDA Greenbook

3.4.2 Endocrine Disruptors

Potential endocrine disrupting compound
S109 | PARCEDC | List of 7074 potential endocrine disrupting compounds (EDCs) by PARC T4.2 | DOI:10.5281/zenodo.10944198

3.4.3 Pesticides

Insecticides
S69 | LUXPEST | Pesticide Screening List for Luxembourg | DOI:10.5281/zenodo.3862688
Active substance -> EU Pesticides database: Not approved
Pesticides -> Organophosphate Insecticides
Environmental transformation -> Pesticides (parent, predecessor)
S60 | SWISSPEST19 | Swiss Pesticides and Metabolites from Kiefer et al 2019 | DOI:10.5281/zenodo.3544759
Pesticide (Trichlorfon) -> USDA PDB

4 Spectral Information

4.1 1D NMR Spectra

1D NMR Spectra

4.1.1 1H NMR Spectra

Spectra ID
Instrument Type
JEOL
Frequency
400 MHz
Solvent
CDCl3
Shifts [ppm]:Intensity
4.55:25.00, 3.94:576.00, 4.53:24.00, 4.52:23.00, 3.93:21.00, 3.88:578.00, 3.91:1000.00
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4.1.2 13C NMR Spectra

1 of 2
Spectra ID
Frequency
50.18 MHz
Solvent
CDCl3
Shifts [ppm]:Intensity
97.57:645.00, 54.83:907.00, 78.30:834.00, 54.68:1000.00, 97.76:579.00, 54.22:957.00, 81.59:875.00, 54.10:946.00
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2 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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4.1.3 31P NMR Spectra

Instrument Name
Bruker HX-90
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 7
View All
Spectra ID
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

109.0 99.99

79.0 61.67

110.0 52.78

145.0 43.77

139.0 33.33

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Notes
instrument=HITACHI M-80
2 of 7
View All
MoNA ID
MS Category
Experimental
MS Type
GC-MS
MS Level
MS1
Instrument
HITACHI M-80
Instrument Type
EI-B
Ionization Mode
positive
Top 5 Peaks

109 99.99

79 61.67

110 52.78

145 43.77

139 33.33

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License
CC BY-NC-SA

4.2.2 LC-MS

1 of 27
View All
Authors
Kevin S. Jewell; Björn Ehlig; Arne Wick
Instrument
TripleTOF 6600 SCIEX
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
40
Fragmentation Mode
CID
Column Name
Zorbax Eclipse Plus C18 2.1 mm x 150 mm, 3.5 um, Agilent
Retention Time
6.251 min
Precursor m/z
256.9299
Precursor Adduct
[M+H]+
Top 5 Peaks

109.0041 999

78.9934 430

82.9438 151

93.0088 56

127.0145 47

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License
dl-de/by-2-0
2 of 27
View All
Authors
Kevin S. Jewell; Björn Ehlig; Arne Wick
Instrument
TripleTOF 6600 SCIEX
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
140
Fragmentation Mode
CID
Column Name
Zorbax Eclipse Plus C18 2.1 mm x 150 mm, 3.5 um, Agilent
Retention Time
6.251 min
Precursor m/z
256.9299
Precursor Adduct
[M+H]+
Top 5 Peaks

46.9674 999

82.9439 337

47.9754 242

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License
dl-de/by-2-0

4.2.3 Other MS

Authors
HASHIMOTO K, KYOTO COLLEGE OF PHARMACY
Instrument
HITACHI M-80
Instrument Type
EI-B
MS Level
MS
Ionization Mode
POSITIVE
Ionization
ENERGY 20 eV
Top 5 Peaks

109 999

79 617

110 528

145 438

139 333

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License
CC BY-NC-SA

4.3 IR Spectra

4.3.1 FTIR Spectra

Technique
FILM
Source of Sample
Chemagro Corporation
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4 Other Spectra

Intense mass spectral peaks: 145 m/z, 185 m/z, 220 m/z
Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, Federal Republic of Germany. 1985., p. 350

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

7.2 FDA Green Book

7.3 Therapeutic Uses

Anthelmintics; Cholinesterase Inhibitors; Insecticides.
National Library of Medicine's Medical Subject Headings. Trichlorfon. Online file (MeSH, 2017). Available from, as of May 24, 2017: https://www.nlm.nih.gov/mesh/2017/mesh_browser/MBrowser.html
Trichlorfon has been used to treat helminthiasis, including ankylostomiasis, ascariasis, trichuriasis, and creeping eruption in human. The expected pharmacological effects of the drug did appear as side effects but these effects were no more severe or frequent than those of other anthelminthics. Trichlorfon is effective for treating even Schistosoma hematobium infection.
Krieger, R. (ed.). Handbook of Pesticide Toxicology. Volume 1, 2nd ed. 2001. Academic Press, San Diego, California., p. 56
/EXPL THER/ Metrifonate (trichlorfon) is an inhibitor of acetylcholinesterase (AChE). It was used as an Alzheimer's disease (AD) drug; however, the application was withdrawn due to adverse effects. Implication of metrifonate for the antioxidant status and regulation of apoptotic processes was evaluated in the present study. Wistar rats (six per group) were exposed subcutaneously to either 60 or 120 mg/kg of body weight of metrifonate and compared with the controls treated with saline only. Cerebral cortex and liver tissues were collected from animals 40 min after exposure. Activities of AChE, glutathione reductase, glutathione-S-transferase, caspase 3, total protein level, thiobarbituric acid reactive substances, reduced glutathione level and ferric reducing antioxidant power (FRAP) were assayed in the tissue samples. Metrifonate had only lower impact on oxidative stress in the liver. Cerebral cortex tissues had decreased AChE and increased caspase 3 activities as well as the FRAP level. Owing to the novel findings, suitability of metrifonate for AD therapy is discussed.
Pohanka M et al; Toxicol Mech Methods 21 (8): 585-90 (2011)
Metrifonate is an excellent drug for the treatment of urinary schistosomiasis in areas with Schistosoma haematobium monoinfection. Toxicity apparently is negligible. Side effects due to the inhibition of acetylcholinesterase are usually scarce, light and transient in nature. At the recommended dosage of 3 time 10 mg/kg the chemotherapeutic potential of metrifonate to cure can be expected to range between 60 and 90%. Each dose of metrifonate reduces egg excretion by almost 90%. Treatment with metrifonate clearly reverses lower and upper renal tract pathology. When appropriately timed with regards to local transmission dynamics the minimal requirement to achieve 99% reduction of egg excretion may be as low as three or four doses spaced over a period of two years.
Feldmeier H, Doehring E; Acta Trop (Basel) 44 (3): 357-68 (1987)
For more Therapeutic Uses (Complete) data for Trichlorfon (13 total), please visit the HSDB record page.

7.4 Drug Warnings

/Metrifonate/ treated individuals should be free from recent exposure to insecticides that might add to the anticholinesterase effect. They also should not receive depolarizing neuromuscular blocking agents for at least 48 hr after treatment.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1133
VET: Do not use in conjunction with or within few days of (before or after) any other cholinesterase inhibitors; avoid use with phenothiazine, phenothiazine tranquilizers, arsenicals, purgatives or drugs producing purgation as side effect. Possibility of adverse reactions in heartworm infested dogs ... suggested. Do not contaminate feed or water except as in product use directions. Apply to cattle as directed only after milking. Skin sensitivity ... reported ... on pets wearing "flea collars." Avoid use in very young, debilitated, and constipated animals, or those with cirrhotic livers or acute infectious diseases.
Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 615
A 60% depression in red /blood/ cell /(cholinesterase)/ ChE and 80% depression in plasma ChE were accompanied by only minor side effects (nausea, vomiting, and/or diarrhea) ... .
WHO; Environ Health Criteria 132: Trichlorfon p. 74 (1992)
In ... /a/ study designed to evaluate the safety and tolerability of relatively high loading doses followed by lower maintenance doses and to determine the maximum tolerated dose of trichlorfon, groups of probable Alzheimer's disease patients were administered either 2.5 mg/kg/day for 14 days followed by 4.0 mg/kg/day for 3 days, then 2.0 mg/kg/day for 14 days or 2.5 mg/kg/day for 14 days followed by 1.5 mg/kg/day for 35 days. RBC acetylcholinesterase inhibition occurred in all groups. Moderate to severe cholinergic effects (muscle cramps, abdominal discomfort, headache, muscle weakness, generalized moderate to severe muscle cramps, weakness, inability to resume daily activities, and coordination difficulties) occurred in 6 of 8 patients given the higher doses (4.0 mg/kg/day for 3 days and 2.0 mg/kg/day for 14 days); mild to moderate cholinergic effects (gastrointestinal disturbances, muscle cramps, and light-headedness/dizziness) occurred among patients given the lower maintenance dose (1.5 mg/kg/day). /Former use/
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V7 934
For more Drug Warnings (Complete) data for Trichlorfon (6 total), please visit the HSDB record page.

8 Food Additives and Ingredients

8.1 Food Additive Classes

JECFA Functional Classes
Veterinary Drug -> INSECTICIDE;

8.2 Evaluations of the Joint FAO / WHO Expert Committee on Food Additives - JECFA

1 of 2
Chemical Name
METRIFONATE
Evaluation Year
2006
ADI
0-2 µg/kg bw
Comments
The 60th & 66th Committees reviewed further information on trichlorfon's pharmacokinetics and genotoxic, reproductive and developmental toxicity, and neurotoxicity. The information did not provide evidence that any of these effects was more sensitive than inhibition of acetylcholinesterase activity, and the Committee concluded that inhibition of acetylcholinesterase is the most relevant end-point for establishing an ADI. The 54th Committee meeting established the ADI for trichlorfon on the basis of a NOEL of 0.2 mg/kg bw/d in a clinical study with Alzheimer disease patients. In this study, the volunteers were given a loading dose of 0.5 mg/kg/d for 2 weeks, followed by a maintenance dose of 0.2 mg/kg/d for 8 weeks. The 54th Committee meeting concluded that the maintenance dose had not significantly enhanced the inhibition of erythrocyte cholinesterase activity established in patients by the loading dose and concluded that the maintenance dose was the NOEL. Because the NOEL was derived from a human study, a safety factor of 10 was applied to the NOEL to derive the ADI. The 60th Committee re-examined the basis on which it had established the ADI and concluded that the dose previously identified as the NOEL was more appropriately considered a LOEL. Furthermore, the Committee recalled that a clear NOEL of 0.2 mg/kg/d for inhibition of erythrocyte cholinesterase activity was established in a 10-year study of toxicity in monkeys treated orally. If that study had been selected as the basis for setting the ADI, a safety factor of 100 would have been applied, resulting in an ADI of 0–2 μg/kg bw. The 60th Committee concluded that an ADI could be derived from the human study by applying an additional factor of 10 to this LOEL such that the amended ADI is 0–2 μg/kg bw. The present Committee concluded that deriving ADIs from studies in diseased human populations, where such data are available, likely represents a worst-case scenario for establishing ADIs. Available data indicate that the pharmacokinetics of trichlorfon were not appreciably different between the study population and healthy subjects. The present Committee confirmed the ADI of 0-2 µg/kg bw for trichlorfon previously established by the 60th Committee.
2 of 2
Chemical Name
TRICHLORFON
Evaluation Year
2006
ADI
0-2 µg/kg bw
Comments
The 60th & 66th Committees reviewed further information on trichlorfon's pharmacokinetics and genotoxic, reproductive and developmental toxicity, and neurotoxicity. The information did not provide evidence that any of these effects was more sensitive than inhibition of acetylcholinesterase activity, and the Committee concluded that inhibition of acetylcholinesterase is the most relevant end-point for establishing an ADI. The 54th Committee meeting established the ADI for trichlorfon on the basis of a NOEL of 0.2 mg/kg bw/d in a clinical study with Alzheimer disease patients. In this study, the volunteers were given a loading dose of 0.5 mg/kg/d for 2 weeks, followed by a maintenance dose of 0.2 mg/kg/d for 8 weeks. The 54th Committee meeting concluded that the maintenance dose had not significantly enhanced the inhibition of erythrocyte cholinesterase activity established in patients by the loading dose and concluded that the maintenance dose was the NOEL. Because the NOEL was derived from a human study, a safety factor of 10 was applied to the NOEL to derive the ADI. The 60th Committee re-examined the basis on which it had established the ADI and concluded that the dose previously identified as the NOEL was more appropriately considered a LOEL. Furthermore, the Committee recalled that a clear NOEL of 0.2 mg/kg/d for inhibition of erythrocyte cholinesterase activity was established in a 10-year study of toxicity in monkeys treated orally. If that study had been selected as the basis for setting the ADI, a safety factor of 100 would have been applied, resulting in an ADI of 0–2 μg/kg bw. The 60th Committee concluded that an ADI could be derived from the human study by applying an additional factor of 10 to this LOEL such that the amended ADI is 0–2 μg/kg bw. The present Committee concluded that deriving ADIs from studies in diseased human populations, where such data are available, likely represents a worst-case scenario for establishing ADIs. Available data indicate that the pharmacokinetics of trichlorfon were not appreciably different between the study population and healthy subjects. The present Committee confirmed the ADI of 0-2 µg/kg bw for trichlorfon previously established by the 60th Committee.

9 Agrochemical Information

9.1 Agrochemical Category

Insecticide
Pesticide active substances -> Insecticides
Insecticides
S69 | LUXPEST | Pesticide Screening List for Luxembourg | DOI:10.5281/zenodo.3862688

9.2 Agrochemical Transformations

Trichlorfon has known environmental transformation products that include Dichlorovinyl phosphate, Demethyl Trichlorfon, DDVP, Desmethyl DDVP, Dimethyl Phosphate, and Trichlorohydroxyethyl-phosphonic acid.
S60 | SWISSPEST19 | Swiss Pesticides and Metabolites from Kiefer et al 2019 | DOI:10.5281/zenodo.3544759
Trichlorfon has known environmental transformation products that include dichlorvos.
S78 | SLUPESTTPS | Pesticides and TPs from SLU, Sweden | DOI:10.5281/zenodo.4687924

9.3 EU Pesticides Data

Active Substance
trichlorfon
Status
Not approved [Reg. (EC) No 1107/2009]
Legislation
2007/356
ADI
0.045 mg/kg bw/day [DAR]
ARfD
0.1 mg/kg bw [DAR]
AOEL
0.09 mg/kg bw/day [DAR]

9.4 USDA Pesticide Data Program

10 Pharmacology and Biochemistry

10.1 MeSH Pharmacological Classification

Cholinesterase Inhibitors
Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. (See all compounds classified as Cholinesterase Inhibitors.)
Anthelmintics
Agents that kill parasitic worms. They are used therapeutically in the treatment of HELMINTHIASIS in man and animal. (See all compounds classified as Anthelmintics.)
Insecticides
Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. (See all compounds classified as Insecticides.)

10.2 ATC Code

P - Antiparasitic products, insecticides and repellents

P02 - Anthelmintics

P02B - Antitrematodals

P02BB - Organophosphorous compounds

P02BB01 - Metrifonate

10.3 Absorption, Distribution and Excretion

Absorbed by skin.
Larranaga, M.D., Lewis, R.J. Sr., Lewis, R.A.; Hawley's Condensed Chemical Dictionary 16th Edition. John Wiley & Sons, Inc. Hoboken, NJ 2016., p. 1364
Trichlorfon ... is not readily absorbed by cotton leaves.
White-Stevens, R. (ed.). Pesticides in the Environment: Volume 1, Part 1, Part 2. New York: Marcel Dekker, Inc., 1971., p. 176
In cow, (32)P-labeled trichlorfon administered orally ... /was/ eliminated in urine, about 65% of administered dose ... /was/ excreted in 12 hr. ... 75% ... of compound of unknown structure. ... Less than 0.2% of administered dose ... in milk ... Blood contained ... max of 15.1 ug equivalent 2 hr after administration, decreased ... to about 1 ug equivalent after 24 hr.
White-Stevens, R. (ed.). Pesticides in the Environment: Volume 1, Part 1, Part 2. New York: Marcel Dekker, Inc., 1971., p. 175
The absorption, distribution, and excretion of trichlorfon in mammals is rapid: about 70-80% of a dose administered orally to mice was excreted during the first 12 hr after treatment. The biological half-life of trichlorfon was 80 min. ...3 hr after an iv injection of (14)CH3O-trichlorfon to rats, trace amounts of radioactivity were found in the liver, lungs, kidney, heart, spleen and blood.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V30 216 (1983)
For more Absorption, Distribution and Excretion (Complete) data for Trichlorfon (15 total), please visit the HSDB record page.

10.4 Metabolism / Metabolites

Trichlorfon and dichlorvos levels were followed in plasma and RBCs of 7 individuals given single oral doses of 7.5-10 mg/kg trichlorfon repeated after 2 wk for treating schistosomiases. The relationship of dichlorvos to trichlorfon in plasma and RBCs was about 1%. A biphasic curve for the elimination of trichlorfon in plasma developed; the first phase had a half-life of 0.4 to 0.6 hr, and the second phase had a half-life of about 3 hr. Clearance of trichlorfon was primarily due to formation of dichlorvos.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V7 929
... Trichlorfon (and its /metabolic/ product dichlorvos) is very rapidly absorbed and cleared in humans. After acute oral treatment of healthy male volunteers with a 2, 5, 7.5, or 12 mg/kg dose of trichlorfon (metrifonate), the maximum blood concentration of trichlorfon was obtained between 12 min and 2 hr and the half-life in blood was about 2 hr. The concentrations of dichlorvos ... closely followed those of trichlorphon at a constant ratio of about 1 to 100. The concentrations of trichlorfon were detectable up to 8 hr, but those of dichlorvos had fallen bellow the level of detection by then. Both plasma and RBC cholinesterases were readily inhibited and were still low after 24 hr - none of the volunteers complained of side effects (and the half-life of ... dichlorvos was about 3.8 hr).
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V7 929
The predominant metabolic pathway that involves cleavage of the P-C phosphonate bond that generates trichloroethanol and dimethyl phosphate which are then excreted in urine. Quantitatively minor pathways of metabolism include demethylation ... and (nonenzymatic) dehydrochlorination of dichlorvos which is rapidly metabolized to dichloroethanol and dimethyl phosphate which are then excreted in urine.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V7 929
Dichlorvos was detected in the brain of mice after ip injection of trichlorfon. Following dermal and intragastric application of trichlorfon to cows, the parent compound and dichlorvos were detected in the milk up to 22 days after application.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V30 216 (1983)
For more Metabolism/Metabolites (Complete) data for Trichlorfon (13 total), please visit the HSDB record page.
Metabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.

10.5 Biological Half-Life

...The half-time of trichlorfon in human plasma is approximately 2 hours.
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additives Series 45: Trichlorfon (2000). Available from, as of February 23, 2006: https://www.inchem.org/documents/jecfa/jecmono/v45je05.htm
The biological half-life of trichlorfon was 80 min /in mice/.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V30 216 (1983)
... Following a 133 mg/kg oral dose, trichlorfon was not detected ... Calculated half-lives /of dichlorvos (a nonenzymatic breakdown product of trichlorfon)/ in /rat/ blood, adipose tissue, muscle, and liver were 7, 11, 10, and 12 days, respectively.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V7 929
After acute oral treatment of healthy male volunteers with a 2, 5, 7.5, or 12 mg/kg dose of trichlorfon (metrifonate) ... the half-life of ... dichlorvos /in blood/ was about 3.8 hr ...
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V7 929

10.6 Transformations

11 Use and Manufacturing

11.1 Uses

EPA CPDat Chemical and Product Categories
The Chemical and Products Database, a resource for exposure-relevant data on chemicals in consumer products, Scientific Data, volume 5, Article number: 180125 (2018), DOI:10.1038/sdata.2018.125
Sources/Uses
Applied to crops, livestock, shrubs, and trees to kill cockroaches, crickets, silverfish, bedbugs, fleas, cattle grubs, flies, ticks, leafminers, and leaf-hoppers; also used to kill fish and domestic animal parasites; [EXTOXNET] Also used as therapeutic anthelmintic (schistosoma); [Merck Index] A general purpose non-agricultural systemic insecticide; Used mostly for home and golf course turf, but also used for ornamentals, food and meat processing facilities (non-food contact surfaces), and ornamental and bait fish ponds; Used in other countries as pour-on cattle treatment; [Reference #2] Used in the EU on fruit trees, vegetables, field crops, and greenhouse crops; [EFSA]
Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013.
Industrial Processes with risk of exposure
Farming (Pesticides) [Category: Industry]
Anthelmintics; Cholinesterase Inhibitors; Insecticides.
National Library of Medicine's Medical Subject Headings. Trichlorfon. Online file (MeSH, 2017). Available from, as of May 24, 2017: https://www.nlm.nih.gov/mesh/2017/mesh_browser/MBrowser.html
For trichlorfon (USEPA/OPP Pesticide Code: 057901) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./
National Pesticide Information Retrieval System's USEPA/OPP Chemical Ingredients Database on Trichlorfon (52-68-6). Available from, as of June 9, 2017: https://npirspublic.ceris.purdue.edu/ppis/
MEDICATION (VET)
Non-systemic insecticide with contact and stomach action. Insecticidal control in agriculture, horticulture, forestry, food storage, gardening, households, and animal husbandry. In particular, control of Diptera, Lepidoptera, Hymenoptera, Hemiptera and Coleoptera on many crops. ...Also used to control household pests, such as flies, cockroaches, fleas, bed bugs, silverfish, ants, etc.; as a fly bait in farm buildings and animal houses; and for control of ectoparasites on domestic animals.
Tomlin CDS, ed. Trichlorfon (52-68-6). In: The e-Pesticide Manual, 13th Edition Version 3.2 (2005-06). Surrey UK, British Crop Protection Council.
For more Uses (Complete) data for Trichlorfon (7 total), please visit the HSDB record page.
This is a man-made compound that is used as a pesticide.

11.1.1 Use Classification

Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients
Veterinary Drug -> INSECTICIDE; -> JECFA Functional Classes
Hazard Classes and Categories -> Mutagens, Teratogens
Environmental transformation -> Pesticides (parent, predecessor)
S60 | SWISSPEST19 | Swiss Pesticides and Metabolites from Kiefer et al 2019 | DOI:10.5281/zenodo.3544759
Insecticides
S69 | LUXPEST | Pesticide Screening List for Luxembourg | DOI:10.5281/zenodo.3862688

11.1.2 Household Products

Household & Commercial/Institutional Products

Information on 3 consumer products that contain Trichlorfon in the following categories is provided:

• Pesticides

• Pet Care

11.2 Methods of Manufacturing

... Reaction of dimethyl hydrogen phosphite with trichloroacetaldehyde.
Muller F et al; Acaricides. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2017). NY, NY: John Wiley & Sons.. Online Posting Date: July 15, 2009
Prepn: W. Lorenz, United States of America patent 2701225 (1955 to Bayer).
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1784

11.3 Impurities

... Impurities are 2,2-dichlorovonyl dimethyl phosphate: dichlorvos (0-0.2%), trichloroacetaldehyde (0-0.05%), dichloroacetaldehyde (0-0.03%), methyl hydrogen 2,2,2-trichloro-1-hydroxyethylphosphonate; demethyl trichlorfon (0-0.03%), and water (less than 0.3%). The technical product also contains phosphoric acid, 2,2,2-trichloro-1-hydroxyethylphosphoric acid, and dimethyl phosphite.
WHO; Environ Health Criteria 132: Trichlorfon p. 13 (1992)

11.4 Formulations / Preparations

Dipterex Technical Insecticide (Bayer Environmental Science): Active ingredient: trichlorfon 80%.
National Pesticide Information Retrieval System's Database on Trichlorfon (52-68-6). Available from, as of June 9, 2017: https://npirspublic.ceris.purdue.edu/ppis/
Dylox 80 Concentrate Insecticide (Bayer Environmental Science): Active ingredient: trichlorfon 80%.
National Pesticide Information Retrieval System's Database on Trichlorfon (52-68-6). Available from, as of June 9, 2017: https://npirspublic.ceris.purdue.edu/ppis/
Dylox 80 Turf and Ornamental Insecticide (Bayer Environmental Science): Active ingredient: trichlorfon 80%.
National Pesticide Information Retrieval System's Database on Trichlorfon (52-68-6). Available from, as of June 9, 2017: https://npirspublic.ceris.purdue.edu/ppis/
Dylox 6.2 Granular Insecticide (Bayer Environmental Science): Active ingredient: trichlorfon 6.2%.
National Pesticide Information Retrieval System's Database on Trichlorfon (52-68-6). Available from, as of June 9, 2017: https://npirspublic.ceris.purdue.edu/ppis/
For more Formulations/Preparations (Complete) data for Trichlorfon (14 total), please visit the HSDB record page.

11.5 Consumption Patterns

INSECTICIDE FOR NON-AGRICULTURAL USES EXCL FORESTS, 40%; FOREST, 30%; VEGETABLES, 20%; COTTON, 10% (1980)
SRI
Estimated US use of trichlorfon, 568,000 lb in 1989, 1,060,000 lbs in 1966.
Gianessi LP; US Pesticide Use Trends 1966-1989: Resources for the Future, Washington, DC (1992)

11.6 U.S. Production

(1977) NOT PRODUCED COMMERCIALLY IN US
SRI
(1982) NOT PRODUCED COMMERCIALLY IN US
SRI

11.7 General Manufacturing Information

The WHO Recommended Classification of Pesticides by Hazard identifies Trichlorfon (technical grade) as Class II: moderately hazardous; Main Use: insecticide.
WHO International Programme on Chemical Safety; The WHO Recommended Classification of Pesticides by Hazard and Guidelines to Classification 2009 p.32 (2010)

12 Identification

12.1 Analytic Laboratory Methods

Method: EPA-RCA 8141B (GC-FPD); Procedure: gas chromatography with flame photometric detector; Analyte: trichchlorfon; Matrix: water, soil, waste samples; Detection Limit: not provided.
National Environmental Methods Index; Analytical, Test and Sampling Methods. Trichlorfon (52-68-6). Available from, as of June 12, 2017: https://www.nemi.gov
Method: EPA-RCA 8141B (GC-NPD); Procedure: gas chromatography with a nitrogen-phosphorus detector (NPD); Analyte: trichlorfon; Matrix: water, soil, waste samples; Detection Limit: not provided.
National Environmental Methods Index; Analytical, Test and Sampling Methods. Trichlorfon (52-68-6). Available from, as of June 12, 2017: https://www.nemi.gov
Product analysis by polarography, or by titration of the chloride ion obtained by hydrolysis.
Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium, 11 th ed., British Crop Protection Council, Surrey, England 1997, p. 1235
Trichlorfon determination in alfalfa by GC/thermionic flame ionization detection; limit of detection: 0.02 mg/kg; Methods for pesticides and plant growth regulators in vegetables by GC/microcoulometric detection; limit of detection; 0.1 mg/kg, in milk by gas chromatography/ electron capture detection 0.01 mg/kg, in animal tissue by GC/ECD; limit of detection 0.1 mg/kg.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V30 212 (1983)
For more Analytic Laboratory Methods (Complete) data for Trichlorfon (17 total), please visit the HSDB record page.

12.2 Clinical Laboratory Methods

HPLC determination in plasma.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1784
The aim of this study was to determine the no-observable-adverse-effect concentration (NOAEC) for trichlorfon, an antiparasitic agent used in aquaculture, in Piractus mesopotamicus (pacu) using acetylcholinesterase (AChE) activity as an end point. Fish were exposed 24 hr/d for 15 d to different concentrations of trichlorfon in tanks of water for which a curve of dissipation was previously determined. Analysis of trichlorfon in water and fish plasma using gas chromatography with electron capture detection (GC-ECD) enabled measurement of limit of detection (LOD) and limit of quantification (LOQ), respectively, to be 3 and 10 ppb. Thirty-six hours after trichlorfon dilution in water, the concentration was below the LOD, and data showed that plasma concentrations did not exceed the LOQ. Apart from the 6.25 ug/L, all concentrations of trichlorfon significantly inhibited plasma and brain AChE activity compared to controls. The AChE activity levels returned to control values in 7 d. These data may be useful to determine the concentration of trichlorfon that destroys parasites without producing adverse effects in fish.
Mataqueiro MI et al; J Toxicol Environ Health A 77 (1-3): 125-32 (2014)
0.1 mg/kg, in milk by gas chromatography/ electron capture detection 0.01 mg/kg, in animal tissue by GC/ECD; limit of detection 0.1 mg/kg
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V30 212 (1983)

13 Safety and Hazards

13.1 Hazards Identification

13.1.1 GHS Classification

1 of 5
View All
Pictogram(s)
Acute Toxic
Irritant
Health Hazard
Environmental Hazard
Signal
Danger
GHS Hazard Statements

H301 (30%): Toxic if swallowed [Danger Acute toxicity, oral]

H302+H312 (47.5%): Harmful if swallowed or in contact with skin [Warning Acute toxicity, oral; acute toxicity, dermal]

H302 (70%): Harmful if swallowed [Warning Acute toxicity, oral]

H312 (47.5%): Harmful in contact with skin [Warning Acute toxicity, dermal]

H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H334 (47.5%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]

H400 (100%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

H410 (100%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

Precautionary Statement Codes

P233, P260, P261, P264, P270, P271, P272, P273, P280, P284, P301+P316, P301+P317, P302+P352, P304+P340, P317, P321, P330, P333+P317, P342+P316, P362+P364, P391, P403, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 80 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

13.1.2 Hazard Classes and Categories

Acute Tox. 3 (30%)

Acute Tox. 4 (70%)

Acute Tox. 4 (47.5%)

Skin Sens. 1 (100%)

Resp. Sens. 1 (47.5%)

Aquatic Acute 1 (100%)

Aquatic Chronic 1 (100%)

Acute toxicity - category 4

Skin sensitisation - category 1

Hazardous to the aquatic environment (acute) - category 1

Hazardous to the aquatic environment (chronic) - category 1

13.1.3 Health Hazards

INHALATION, INGESTION, AND SKIN ABSORPTION. Inhibits cholinesterase. Headache, depressed appetite, nausea, miosis are symptoms of light exposures. Moderate effects are peritoneal paralysis, diarrhea, salivation, lacrimation, sweating, dyspnea, substernal tightness, slow pulse, tremors, muscular cramps and ataxia. Severe symptoms are: pyrexia, cyanosis, pulmonary edema, areflexia, loss of sphincter control, paralysis, coma, heart block, shock and respiratory failure. EYES: Increases permeability of blood vessels in anterior eye. Reduces corneal sensitivity with glaucoma, abnormalities in intraocular tension or decreased visual acuity. (USCG, 1999)
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.

13.1.4 Fire Hazards

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:

Combustible material: may burn but does not ignite readily. Containers may explode when heated. Those substances designated with a (P) may polymerize explosively when heated or involved in a fire. Runoff may pollute waterways. Substance may be transported in a molten form. (ERG, 2024)

Combustible.

13.1.5 Hazards Summary

Trichlorfon is classified as moderately toxic with an LD50 of 450-650 mg/kg in rats. Skin sensitivity has been reported. Delayed polyneuropathy has occurred in patients who ingested large amounts. [EXTOXNET] A small number of the organophosphates (OPs) can Induce Delayed Neuropathy (OPIDN). OPIDN usually occurs after ingestion and is usually nonoccupational. [Levy, p. 431] A slow release cholinesterase inhibitor; Non-enzymatically transformed into dichlorvos, the active compound; [Merck Index] A cholinesterase inhibitor that may cause nervous system effects (convulsions, respiratory failure, and death); May cause skin sensitization; Can be absorbed through skin; [ICSC] Reports of delayed neuropathy and skin sensitivity in humans; [HSDB] Produces the OP pesticide dichlorvos (DDVP) on degradation; In a study to evaluate use for treatment of Alzheimer's disease, the LOEL (plasma and erythrocyte cholinesterase inhibition) was 5.0 mg/kg/day for a single oral dose in humans; [Reference #2] The average of two baseline respective cholinesterase activity determinations three days apart, with no exposures to enzyme inhibiting pesticides for at least 30 days, is recommended for each worker prior to exposure to cholinesterase inhibitors because of large inter-individual differences in published baseline values. To be established at least once a year. Removal from workplace exposures is recommended until the cholinesterase activity returns to within 20% of baseline. [TLVs and BEIs] See Dichlorvos.
Levy - Levy BS, Wegman DH, Baron SL, Sokas RK (eds). _Occupational and Environmental Health: Recognizing and Preventing Disease and Injury, _6th Ed. Oxford: Oxford University Press, 2011., p. 431
Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013.
TLVs and BEIs - _Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices. _Cincinnati: ACGIH, 2020.

13.1.6 Fire Potential

This material may burn, but does not ignite readily.
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 6th Edition Volume 1: A-K,Volume 2: L-Z. William Andrew, Waltham, MA 2012, p. 2605

13.1.7 Skin, Eye, and Respiratory Irritations

An eye irritant.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3529

13.2 First Aid Measures

Inhalation First Aid
Fresh air, rest. Refer for medical attention.
Skin First Aid
Remove contaminated clothes. Rinse and then wash skin with water and soap. Refer for medical attention .
Eye First Aid
First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.
Ingestion First Aid
Induce vomiting (ONLY IN CONSCIOUS PERSONS!). Rest. Refer for medical attention .

13.2.1 First Aid

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control center even if no symptoms (such as redness or irritation) develop. IMMEDIATELY transport the victim to a hospital for treatment after washing the affected areas.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.

INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, administer a slurry of activated charcoal in water and simultaneously call a hospital or poison control center. IMMEDIATELY transport the victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.3 Fire Fighting

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:

SMALL FIRE: Dry chemical, CO2 or water spray.

LARGE FIRE: Water spray, fog or regular foam. If it can be done safely, move undamaged containers away from the area around the fire. Dike runoff from fire control for later disposal. Avoid aiming straight or solid streams directly onto the product.

FIRE INVOLVING TANKS, RAIL TANK CARS OR HIGHWAY TANKS: Fight fire from maximum distance or use unmanned master stream devices or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks in direct contact with flames. For massive fire, use unmanned master stream devices or monitor nozzles; if this is impossible, withdraw from area and let fire burn. (ERG, 2024)

In case of fire in the surroundings, use appropriate extinguishing media.

13.3.1 Fire Fighting Procedures

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
If material involved in fire: Extinguish fire using agent suitable for type surrounding fire. (Material itself does not burn, or burns with difficulty.)
Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 900
For small fires, use dry chemical, carbon dioxide, water spray, or foam. For large fires, use water spray, fog, or foam. ... If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water pray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors, or shows any signs of deforming), withdraw immediately to a secure position. ... The only respirators recommended for firefighting are self-contained breathing apparatuses that have full face-pieces and are operated in a pressure-demand or other positive-pressure mode.
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 6th Edition Volume 1: A-K,Volume 2: L-Z. William Andrew, Waltham, MA 2012, p. 2605

13.3.2 Firefighting Hazards

Special hazards arising from the substance or mixture: Carbon oxides, oxides of phosphorus, hydrogen chloride gas.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html

13.4 Accidental Release Measures

13.4.1 Isolation and Evacuation

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:

IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.

SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.

FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

13.4.2 Spillage Disposal

Personal protection: filter respirator for organic gases and particulates adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Do NOT wash away into sewer. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Then store and dispose of according to local regulations.

13.4.3 Cleanup Methods

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Environmental considerations - Land spill: Dig a pit, pond, lagoon, holding area to contain liquid or solid material. Cover solids with a plastic sheet to prevent dissolving in rain or fire fighting water. Dike surface flow using soil, sand bags, foamed polyurethane, or foamed concrete.
Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 900
Environmental considerations - Water spill: Use natural barriers or oil control booms to limit spill travel. Use natural deep water pockets, excavated lagoons, or sand bag barriers to trap material at bottom. Remove trapped material with suction hoses.
Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 900
As for other organophosphorus pesticides, stay upwind; keep out of low areas. Ventilate closed spaced before entering them. Wear positive-pressure breathing apparatus and special protective clothing. Do not touch spilled material; stop leak if you can do so without risk. Use water spray to reduce vapors. Small spills: Absorb with sand or other noncombustible absorbent material and place into containers for later disposal. Small dry spills: With clean shovel place material into clean dry containers and cover; move containers from spill area. Large spills: Dike far ahead of spill for later disposal. Ventilate area after cleanup is complete. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters.
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 6th Edition Volume 1: A-K,Volume 2: L-Z. William Andrew, Waltham, MA 2012, p. 2605

13.4.4 Disposal Methods

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.
SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.
Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Add a combustible solvent and burn in a furnace equipped with an afterburner and an alkali scrubber. In accordance with 40CFR165, follow recommendations for the disposal of pesticides and pesticide containers. Must be disposed properly by following package label directions or by contacting your local or federal environmental control agency, or by contacting your regional EPA office.
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 6th Edition Volume 1: A-K,Volume 2: L-Z. William Andrew, Waltham, MA 2012, p. 2605
Trichlorofon initially hydrolyzes to the more toxic compound dichlorvos at pH 8 and 37.5 °C, but is essentially 100% hydrolyzed in approximately 24 hr to nontoxic products which can be mixed with a portion of soil rich in organic matter and buried. Recommendable methods: Incineration, hydrolysis, and landfill. Peer-review: Large amount of trichlorofon should be incinerated at high temperature in a unit with effluent gas scrubbing. (Peer-review conclusions of a IRPTC expert consultation (May 1985))
United Nations. Treatment and Disposal Methods for Waste Chemicals (IRPTC File). Data Profile Series No. 5. Geneva, Switzerland: United Nations Environmental Programme, Dec. 1985., p. 232

13.4.5 Preventive Measures

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
For more Preventive Measures (Complete) data for Trichlorfon (11 total), please visit the HSDB record page.

13.5 Handling and Storage

13.5.1 Nonfire Spill Response

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:

ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area. Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. Cover with plastic sheet to prevent spreading. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. DO NOT GET WATER INSIDE CONTAINERS. (ERG, 2024)

13.5.2 Safe Storage

Separated from strong bases and food and feedstuffs. Keep in a well-ventilated room.

13.5.3 Storage Conditions

Keep container tightly closed in a dry and well-ventilated place. Storage class (TRGS 510): Non Combustible Solids.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Store in a secure poison location. ... Store in tightly closed containers in a cool, well-ventilated area away from alkaline materials. Where possible, automatically transfer material from other storage containers to process containers.
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 6th Edition Volume 1: A-K,Volume 2: L-Z. William Andrew, Waltham, MA 2012, p. 2605

13.6 Exposure Control and Personal Protection

Exposure Summary
Biological Exposure Indices (BEI) [ACGIH] - Acetylcholinesterase activity in red blood cells = 70% of individual's baseline; Butylcholinesterase activity in serum or plasma = 60% of individual's baseline; Sample at end of shift; [TLVs and BEIs]
ACGIH - Documentation of the TLVs and BEIs, 7th Ed. Cincinnati: ACGIH Worldwide, 2020.
TLVs and BEIs - _Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices. _Cincinnati: ACGIH, 2020.

13.6.1 Threshold Limit Values (TLV)

0.1 [mg/m3], inhalable fraction
8 hr Time Weighted Avg (TWA): 1 mg/cu m, Inhalable fraction
American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH 2017, p. 59
Peak Exposure Recommendation: Transient increases in workers' exposure levels may exceed 3 times the value of the TLV-TWA level for no more than 15 minutes at a time, on no more than 4 occasions spaced 1 hour apart during a workday, and under no circumstances should they exceed 5 times the value of the TLV-TWA level. In addition, the 8-hour TWA is not to be exceeded for an 8-hour work period.
American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH 2017, p. 5
A4; Not classifiable as a human carcinogen.
American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH 2017, p. 59
Biological Exposure Index (BEI): Determinant: Cholinesterase activity in red blood cells; Sampling Time: Discretionary; BEI: 70% of individual's baseline. The determinant is nonspecific, since it is also observed after exposure to other chemicals. /Acetylcholinesterase Inhibiting Pesticides/
American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH 2017, p. 112

2017 Notice of Intended Changes (NIC): These substances, with their corresponding indices, comprise those for which (1) a BEI is proposed for the first time, (2) a change in the Adopted index is proposed, (3) retention as an NIC is proposed, or (4) withdrawal of the Documentation and adopted BEI is proposed. In each case, the proposals should be considered trial indices during the period they are on the NIC. These proposals were ratified by the ACGIH Board of Directors and will remain on the NIC for approximately one year following this ratification. If the Committee neither finds nor receives any substantive data that change its scientific opinion regarding an NIC BEI, the Committee may then approve its recommendation to the ACGIH Board of Directors for adoption. If the Committee finds or receives substantive data that change its scientific opinion regarding an NIC BEI, the Committee may change its recommendation to the ACGIH Board of Directors for the matter to be either retained on or withdrawn from the NIC. Chemical: Cholinesterase Inhibiting Pesticides. /Cholinesterase Inhibiting Pesticides/

Table: Cholinesterase Inhibiting Pesticides

Determinant
Acetylcholinesterase activity in red blood cells
Sampling Time
End of shift
BEI
70% of individual's baseline activity
Notation
The determinant is nonspecific, since it is also observed after exposure to other chemicals.
Determinant
Butyrylcholinesterase activity in serum or plasma
Sampling Time
End of shift
BEI
60% of individual's baseline activity
Notation
The determinant is nonspecific, since it is also observed after exposure to other chemicals.

American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH 2017, p. 120
(inhalable fraction and vapour): 0.1 mg/m
TLV-TWA (Time Weighted Average)
1 mg/m³ (inhalable particulate matter) [2003]

13.6.2 Inhalation Risk

Evaporation at 20 °C is negligible; a harmful concentration of airborne particles can, however, be reached quickly when dispersed.

13.6.3 Effects of Short Term Exposure

The substance may cause effects on the nervous system by a cholinesterase inhibiting effect. This may result in convulsions, respiratory failure and death. Cholinesterase inhibition. Exposure at high levels could cause death. The effects may be delayed. Medical observation is indicated.

13.6.4 Effects of Long Term Exposure

Repeated or prolonged contact may cause skin sensitization. The substance may have effects on the nervous system. Cholinesterase inhibition. Cumulative effects are possible. See Acute Hazards/Symptoms.

13.6.5 Acceptable Daily Intakes

FAO/WHO ADI: 0.04 mg/kg
FAO/WHO; Pesticide Residues in Food - 1987. Evaluations Part 1 - Residues p.192 Plant & Prod Protect Paper 86/1 (1987)

13.6.6 Allowable Tolerances

Tolerances are established for residues of the insecticide trichlorfon (dimethyl (2,2,2-trichloro-1-hydroxyethyl) phosphonate) in or on the following food commodities:
Commodity
Cattle, fat (There are no USA registrations for cattle commodities as of June 24, 1999)
Parts per million
0.5
Commodity
Cattle, meat (There are no USA registrations for cattle commodities as of June 24, 1999)
Parts per million
0.2
Commodity
Cattle, meat byproducts (There are no USA registrations for cattle commodities as of June 24, 1999)
Parts per million
0.1
40 CFR 180.198 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 5, 2017: https://www.ecfr.gov

13.6.7 Personal Protective Equipment (PPE)

Safety glasses, all-purpose canister mask, sleeve-closed gown, gloves and long boots. (USCG, 1999)
U.S. Coast Guard. 1999. Chemical Hazard Response Information System (CHRIS) - Hazardous Chemical Data. Commandant Instruction 16465.12C. Washington, D.C.: U.S. Government Printing Office.
Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Skin protection: Handle with gloves.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Wear protective gloves and clothing to prevent any reasonable probability of skin contact. ... All protective clothing (suits, gloves, footwear, headgear) should be clean, available each day, and put on before work. ... Wear dust-proof chemical goggles and face shield unless full-face-piece respiratory protection is worn.
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 6th Edition Volume 1: A-K,Volume 2: L-Z. William Andrew, Waltham, MA 2012, p. 2605

13.6.8 Preventions

Fire Prevention
NO open flames.
Exposure Prevention
PREVENT DISPERSION OF DUST! STRICT HYGIENE! AVOID EXPOSURE OF (PREGNANT) WOMEN! AVOID EXPOSURE OF ADOLESCENTS AND CHILDREN! IN ALL CASES CONSULT A DOCTOR!
Inhalation Prevention
Use local exhaust or breathing protection.
Skin Prevention
Protective gloves. Protective clothing.
Eye Prevention
Wear face shield or eye protection in combination with breathing protection.
Ingestion Prevention
Do not eat, drink, or smoke during work.

13.7 Stability and Reactivity

13.7.1 Air and Water Reactions

This chemical decomposes at higher temperatures in water and at pH <5.5. It is sensitive to prolonged exposure to moisture. It is unstable in alkaline solutions.

13.7.2 Reactive Group

Alcohols and Polyols

Halogenated Organic Compounds

Sulfonates, Phosphonates, and Thiophosphonates, Organic

13.7.3 Reactivity Profile

TRICHLORFON is incompatible with alkalis. It is corrosive to black iron and mild steel. It is corrosive to metals. It is subject to hydrolysis. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

13.7.4 Hazardous Reactivities and Incompatibilities

Incompatible materials: Strong oxidizing agents.
Sigma-Aldrich; Safety Data Sheet for Trichlorfon. Product Number: 45698, Version 5.5 (Revision Date 08/10/2015). Available from, as of May 23, 2017: https://www.sigmaaldrich.com/safety-center.html
Incompatibilities: Alkaline materials: lime, lime sulfur, etc. Corrosive to iron and steel.
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 6th Edition Volume 1: A-K,Volume 2: L-Z. William Andrew, Waltham, MA 2012, p. 2604

13.8 Transport Information

13.8.1 DOT Emergency Guidelines

/GUIDE 131 FLAMMABLE LIQUIDS - TOXIC/ Fire or Explosion: HIGHLY FLAMMABLE: Will be easily ignited by heat, sparks or flames. Vapors may form explosive mixtures with air. Vapors may travel to source of ignition and flash back. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapor explosion and poison hazard indoors, outdoors or in sewers. Those substances designated with a (P) may polymerize explosively when heated or involved in a fire. Runoff to sewer may create fire or explosion hazard. Containers may explode when heated. Many liquids are lighter than water. /Organophosphorus pesticide, liquid, flammable, poisonous; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, poisonous, flammable; Organophosphorus pesticide, liquid, toxic, flammable/
U.S. Department of Transportation. 2016 Emergency Response Guidebook. Washington, D.C. 2016
/GUIDE 131 FLAMMABLE LIQUIDS - TOXIC/ Health: TOXIC; may be fatal if inhaled, ingested or absorbed through skin. Inhalation or contact with some of these materials will irritate or burn skin and eyes. Fire will produce irritating, corrosive and/or toxic gases. Vapors may cause dizziness or suffocation. Runoff from fire control or dilution water may cause pollution. /Organophosphorus pesticide, liquid, flammable, poisonous; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, poisonous, flammable; Organophosphorus pesticide, liquid, toxic, flammable/
U.S. Department of Transportation. 2016 Emergency Response Guidebook. Washington, D.C. 2016
/GUIDE 131 FLAMMABLE LIQUIDS - TOXIC/ Public Safety: CALL Emergency Response Telephone Number on Shipping Paper first. If Shipping Paper not available or no answer, refer to appropriate telephone number listed on the inside back cover. As an immediate precautionary measure, isolate spill or leak area for at least 50 meters (150 feet) in all directions. Keep unauthorized personnel away. Stay upwind, uphill and/or upstream. Ventilate closed spaces before entering. /Organophosphorus pesticide, liquid, flammable, poisonous; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, poisonous, flammable; Organophosphorus pesticide, liquid, toxic, flammable/
U.S. Department of Transportation. 2016 Emergency Response Guidebook. Washington, D.C. 2016
/GUIDE 131 FLAMMABLE LIQUIDS - TOXIC/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible. /Organophosphorus pesticide, liquid, flammable, poisonous; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, poisonous, flammable; Organophosphorus pesticide, liquid, toxic, flammable/
U.S. Department of Transportation. 2016 Emergency Response Guidebook. Washington, D.C. 2016
For more DOT Emergency Guidelines (Complete) data for Trichlorfon (16 total), please visit the HSDB record page.

13.8.2 Shipping Name / Number DOT/UN/NA/IMO

UN 2784; Organophosphorus pesticides, liquid, flammable, toxic, flash point less than 23 °C
UN 2783; Organophosphorus pesticides, solid, toxic
UN 3017; Organophosphorus pesticides, liquid, toxic, flammable, flash point not less than 23 °C
UN 3018; Organophosphorus pesticides, liquid, toxic
For more Shipping Name/ Number DOT/UN/NA/IMO (Complete) data for Trichlorfon (8 total), please visit the HSDB record page.

13.8.3 Standard Transportation Number

49 403 75; Trichlorfon (agricultural insecticides, not elsewhere classified, liquid)
49 403 76; Trichlorfon (agricultural insecticides, not elsewhere classified, other than liquid)
49 403 77; Trichlorfon (insecticides, other than agricultural, not elsewhere classified)

13.8.4 Shipment Methods and Regulations

No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./
49 CFR 171.2 (USDOT); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 14, 2017: https://www.ecfr.gov
The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials. Organophosphorus pesticide, solid, toxic; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, toxic, flammable; and Organophosphorus pesticide, liquid, toxic are included on the dangerous goods list. /Organophosphorus pesticide, solid, toxic; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, toxic, flammable; and Organophosphorus pesticide, liquid, toxic/
International Air Transport Association. Dangerous Goods Regulations. 57th Edition. Montreal, Quebec Canada. 2016., p. 292
The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article. /Organophosphorus pesticide, solid, toxic; Organophosphorus pesticide, liquid, flammable, toxic, flashpoint less than 23 °C; Organophosphorus pesticide, liquid, toxic, flammable, flashpoint not less than 23 °C; and Organophosphorus pesticide, liquid, toxic are included on the dangerous goods list. /Organophosphorus pesticide, liquid, flammable, toxic, flashpoint less than 23 °C; Organophosphorus pesticide, liquid, toxic, flammable, flashpoint not less than 23 °C; and Organophosphorus pesticide, liquid, toxic/
International Maritime Organization. IMDG Code. International Maritime Dangerous Goods Code Volume 2 2014, p. 135, 149

13.8.5 DOT Label

Poison

13.8.6 Packaging and Labelling

Do not transport with food and feedstuffs. Marine pollutant.

13.8.7 EC Classification

Symbol: Xn, N; R: 22-43-50/53; S: (2)-24-37-60-61

13.8.8 UN Classification

UN Hazard Class: 6.1; UN Pack Group: III

13.9 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: Phosphonic acid, P-(2,2,2-trichloro-1-hydroxyethyl)-, dimethyl ester
Status Regulation (EC)
2007/356
New Zealand EPA Inventory of Chemical Status
Trichlorfon: Does not have an individual approval but may be used under an appropriate group standard

13.9.1 Clean Water Act Requirements

Trichlorfon is designated as a hazardous substance under section 311(b)(2)(A) of the Federal Water Pollution Control Act and further regulated by the Clean Water Act Amendments of 1977 and 1978. These regulations apply to discharges of this substance. This designation includes any isomers and hydrates, as well as any solutions and mixtures containing this substance.
40 CFR 116.4 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 5, 2017: https://www.ecfr.gov

13.9.2 CERCLA Reportable Quantities

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 100 lb or 45.4 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).
40 CFR 302.4 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 5, 2017: https://www.ecfr.gov

13.9.3 FIFRA Requirements

Tolerances are established for residues of the insecticide trichlorfon (dimethyl (2,2,2-trichloro-1-hydroxyethyl) phosphonate) in or on the following food commodities:
Commodity
Cattle, fat (There are no USA registrations for cattle commodities as of June 24, 1999)
Commodity
Cattle, meat (There are no USA registrations for cattle commodities as of June 24, 1999)
Commodity
Cattle, meat byproducts (There are no USA registrations for cattle commodities as of June 24, 1999)
40 CFR 180.198 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 5, 2017: https://www.ecfr.gov
EPA has concluded, after completing its assessment of the cumulative risks associated with exposures to all of the OPs /including trichlorfon/, that: (1) the pesticides covered by the IREDs that were pending the results of the OP cumulative assessment (listed in Attachment A) are indeed eligible for reregistration; and (2) the pesticide tolerances covered by the IREDs and TREDs that were pending the results of the OP cumulative assessment (listed in Attachment A) meet the safety standard under Section 408(b)(2) of the FFDCA. Thus, with regard to the OPs, EPA has fulfilled its obligations as to FFDCA tolerance reassessment and FIFRA reregistration, other than product-specific reregistration.
USEPA/Office of Prevention, Pesticides and Toxic Substances; Reregistration Eligibility Decision (RED) for Trichlorfon p.1 (July 2006). Available from, as of June 20, 2017: https://www.epa.gov/pesticides/reregistration/status.htm
Based on a review of generic data and public comments on the Agency's revised risk assessments for the active ingredient trichlorfon, the Agency has sufficient information on the human health effects of trichlorfon to make an interim decision as part of the tolerance reassessment process under FQPA. Because the Agency has not yet completed its cumulative risk assessment for the OPs, this interim decision does not fully address tolerance reassessment as required by Section 408(q) of the FQPA; however, the Agency has completed its assessment of risk from dietary exposure to trichlorfon alone. When the cumulative assessment is considered, the FQPA tolerance reassessment requirement will be completed. Nothing in this report precludes the Agency from making further FQPA determinations and tolerance-related rulemaking that may be required on this pesticide or any other in the future. The Agency has also not considered risks associated with exposure to DDVP resulting from trichlorfon use. DDVP, although a trichlorfon degradate, is a registered OP pesticide that is currently undergoing reregistration. Once the DDVP IRED is complete, the Agency will determine whether the DDVP exposure resulting from trichlorfon use poses risk concerns. The Agency may determine that further action is necessary after assessing the cumulative risk of the organophosphate class. At that time, the Agency may also address any other risk concerns that may arise including risks associated with DDVP exposure. ... The Agency has determined that aggregate dietary risk from exposure to trichlorfon may exceed the Agency's level of concern for children 1-6 years when the source of drinking water is surface water. Therefore, mitigation measures are needed at this time to address this concern.
USEPA/Office of Prevention, Pesticides and Toxic Substances; Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk Management Decision (TRED) for Trichlorfon p.30 EPA 738-R-01-009 (September 2001). Available from, as of June 20, 2017: https://www.epa.gov/pesticides/reregistration/status.htm
Based on the reviews of the generic data for the active ingredient Trichlorfon, the Agency has sufficient information on the health effects of Trichlorfon and on its potential for causing adverse effects in fish and wildlife and the environment. Where the potential for adverse effects was identified, the Agency and the registrant agreed upon risk mitigation measures. The Agency has determined that all Trichlorfon products, labeled for non-food uses as specified in this Reregistration Eligibility Decision, will not pose unreasonable risks or adverse effects to humans or the environment. Therefore, the Agency concludes that products containing Trichlorfon are eligible for reregistration if labeing and other changes specified in this document are implemented.
USEPA/Office of Prevention, Pesticides and Toxic Substances; Reregistration Eligibility Decision Document for Trichlorfon p.42 EPA 738-R-96-017 (January 1997). Available from, as of June 20, 2017: https://www.epa.gov/pesticides/reregistration/status.htm
As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer safety standards, such as those described in the Food Quality Protection Act of 1996. Trichlorfon is found on List A, which contains most pesticides that are used on foods and, hence, have a high potential for human exposure. List A consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA issued registration standards prior to FIFRA '88. Case No: 0104; Pesticide type: insecticide; Registration Standard Date: 06/30/84; Case Status: RED Approved 09/95; OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): trichlorfon; Data Call-in (DCI) Date(s): 09/10/91, 03/03/95, 02/14/97; AI Status: OPP has completed a Reregistration Eligibility Decision (RED) document for the case/AI.
United States Environmental Protection Agency/ Prevention, Pesticides and Toxic Substances; Status of Pesticides in Registration, Reregistration, and Special Review. (1998) EPA 738-R-98-002, p. 154

13.9.4 FDA Requirements

Oral dosage form new animal drugs. Mebendazole and trichlorfon powder. ... Indications for use: It is used in horses for the treatment of infections of bots (Gastrophilus intestinalis and G. nasalis), large roundworms (Parascaris equorum), large strongyles (Strongylus edentatus, S. equinus, S. vulgaris), small strongyles, and pinworms (Oxyuris equi.)
21 CFR 520.1326a (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of Junw 5, 2017: https://www.ecfr.gov
Oral dosage form new animal drugs. Mebendazole and trichlorfon paste. ... Indications for use: It is used in horses for the treatment of infections of bots (Gastrophilus intestinalis and G. nasalis), large roundworms (Parascaris equorum), large strongyles (Strongylus edentatus, S. equinus, S. vulgaris), small strongyles, and pinworms (Oxyuris equi.)
21 CFR 520.1326b (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 5, 2017: https://www.ecfr.gov
Oral dosage form new animal drugs. Oxfendazole and trichlorfon paste. ... Indications for use: The drug is used in horses for removal of bots (Gasterophilus intestinalis, 2nd and 3rd instars; G. nasalis, 3rd instar) and the following gastrointestinal worms: Large roundworms (Parascaris equorum), pinworms (Oxyuris equi), adult and 4th stage larvae; large strongyles (Strongylus edentatus, S. vulgaris, and S. equinus); and small strongyles.
21 CFR 520.1631 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 5, 2017: https://www.ecfr.gov
Oral dosage form new animal drugs. Thiabendazole with trichlorfon. ... Indications for use /in horses/. For the treatment and control of bots (Gasterophilus spp.), large strongyles (Strongylus spp.), small strongyles (genera Cyathostomum, Cylicobrachytus, Craterostomum, Oesophagodontus, Poteriostomum), pinworms (Oxyuris spp., Strongyloides spp.), and ascarids (Parascaris spp.).
21 CFR 520.2380e (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 5, 2017: https://www.ecfr.gov
For more FDA Requirements (Complete) data for Trichlorfon (7 total), please visit the HSDB record page.

13.10 Other Safety Information

Chemical Assessment

IMAP assessments - Phosphonic acid, (2,2,2-trichloro-1-hydroxyethyl)-, dimethyl ester: Environment tier I assessment

IMAP assessments - Phosphonic acid, (2,2,2-trichloro-1-hydroxyethyl)-, dimethyl ester: Human health tier I assessment

13.10.1 Toxic Combustion Products

Poisonous gases are produced in fire, including chlorine and phosphorus oxides.
Pohanish, R.P. (ed). Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens 6th Edition Volume 1: A-K,Volume 2: L-Z. William Andrew, Waltham, MA 2012, p. 2605

13.10.2 History and Incidents

Of 15 live births in one Hungarian village in 1989-90, 11 (73%) were affected by congenital abnormalities and 6 were twins. Of the 11, 4 had Down's syndrome. Likely causes of such clusters (known teratogenic factors, familial inheritance, consanguinity) were excluded. A case control study and environmental investigations pointed the finger of suspicion at the excessive use of trichlorfon at local fish farms. The content of this chemical was very high in fish (100 mg/kg) and several pregnant women, including all mothers of babies with Down syndrome, had consumed contaminated fish in the critical period for the congenital abnormalities observed.
Czeizel AE et al; Lancet 341 (8844): 539-42 (1993)

13.10.3 Special Reports

WHO; Environmental Health Criteria 132: Trichlorfon (1992)[Available from, as of May 24, 2017: http://www.inchem.org/documents/ehc/ehc/ehc132.htm]
USEPA/Office of Prevention, Pesticides and Toxic Substances; Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk Management Decision (TRED) for Trichlorfon EPA 738-R-01-009 (September 2001). EPA issues a TRED for a pesticide that requires tolerance reassessment decisions, but does not require a reregistration eligibility decision at present because: the pesticide was initially registered after November 1, 1984, and by law is not included within the scope of the reregistration program; EPA completed a RED for the pesticide before FQPA was enacted on August 3, 1996; or the pesticide is not registered for use in the U.S. but tolerances are established that allow crops treated with the pesticide to be imported from other countries.[Available from, as of June 20, 2017: http://www.epa.gov/pesticides/reregistration/status.htm]
USEPA/Office of Prevention, Pesticides and Toxic Substances; Reregistration Eligibility Decision Document for Trichlorfon EPA 738-R-96-017 (January 1997). The RED summarizes the risk assessment conclusions and outlines any risk reduction measures necessary for the pesticide to continue to be registered in the USA.[Available from, as of June 20, 2017: http://www.epa.gov/pesticides/reregistration/status.htm]

14 Toxicity

14.1 Toxicological Information

14.1.1 Toxicity Summary

IDENTIFICATION AND USE: Trichlorfon is a white, crystalline solid. It is used as anthelmintic drug and systemic insecticide. HUMAN STUDIES: Trichlorfon, an organophosphate, has a moderately potent anticholinesterase activity. 379 cases of trichlorfon poisoning were reviewed, and in some cases (3%), acute poisonings were accompanied by loss of memory and problem-solving ability, delirium, depression and anxiety, psychomotor stimulation, hallucinations, and paranoid delusions; in other cases (21%), poisoning was accompanied by a delayed type polyneuropathy. Of 15 live births in one Hungarian village in 1989-90, 11 (73%) were affected by congenital abnormalities and six were twins. Of the 11, four had Down's syndrome. The likely causes of such clusters were excluded. A case control study and environmental investigations revealed the excessive use of trichlorfon at local fish farms. Trichlorfon content was very high in fish (100 mg/kg) and several pregnant women, including all mothers of babies with Down syndrome, had consumed contaminated fish in the critical period for the congenital abnormalities observed. Trichlorfon demonstrated clastogenic, mutagenic, and DNA damaging effects in human lymphocytes in vitro. Significant and persistent increases (lasting at least 180 days after exposure) in aneuploidy in lymphocytes of individuals who attempted suicide by using trichlorfon were reported. ANIMAL STUDIES: Trichlorfon was a moderate contact allergen in the skin. When applied to the eyes of rabbits it has short lasting miotic effect and produces little or no irritation. In rats given daily oral doses of 300 mg/kg body weight technical trichlorfon for 5 days, brain edema, congestion of organs, fatty degeneration, and glycogen depletion of the liver, glycogen depletion of the heart muscle and emphysema and local inflammation in the lungs were observed. Significant cholinesterase depression was noted at 300 mg/kg in rats. The dietary level of 500 ppm (about 10.5 mg/kg/day) inhibited RBC cholinesterase activity in dogs. Trichlorfon does not have a cumulative effect. There was no significant difference in the incidence of tumors between treated and control groups in mice or hamsters. A single 80 mg/kg body weight dose administered to rats orally by gavage on day 13 of pregnancy caused an increased number of embryonic deaths, a decreased number of live fetuses and increased fetal anomalies, such as exencephaly and failure of eyelids to close; administration of 8 mg/kg body weight throughout pregnancy produced no teratogenic manifestations. Trichlorfon did not induce mutation in Drosophila melanogaster, but because of high toxicity, only low doses could be tested. Trichlorfon induces gene mutation in Salmonella typhimurium and Escherichia coli and in Saccharomyces cerevisiae. It also induces a mitotic crossing over, gene conversion, and mitotic recombination. The positive results in microorganisms indicate that trichlorfon induces mainly base-pair substitution or mutation in the absence of metabolic activation. Trichlorfon also induces a chlorophyll mutation and chromosomal damage in plants. ECOTOXICITY STUDIES: Trichlorfon is moderately toxic for fish and moderately to highly toxic for aquatic arthropods. Trichlorfon applied to ponds at the rate of 1 mg/liter water destroyed the food invertebrates for fish. Large numbers of zooplankton, rotifers, and crustacea died in the first 24 hours after treatment, whereas benthos died during the first week. The affected fauna community recovered slowly. Trichlorfon treatment deprived the fish of valuable foods, such as crustacean and bottom fauna, for as long as 1 month after treatment. No effects on numbers, breeding pairs, nesting success, or mortality of forest songbirds were seen following aerial application of trichlorfon. An observed reduction in singing and increased feeding activity may have been the result of a reduction in food organisms. Trichlorfon was teratogenic for zebrafish embryos leading to anomalies in the absorption of the yolk sac, spine bending and pericardial edemas. Immunological responses and immune gene expressions of prawn exposed to trichlorfon at 0.4 mg/L for 24 hr were perturbed, thus causing a deficiency in immunity and subsequent increased susceptibility to pathogen infections. Trichlorfon influenced fish plasma antioxidative status, caused lipid peroxidation then resulted in hepatocytes apoptosis.
Trichlorfon is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

14.1.2 RAIS Toxicity Values

Oral Acute Reference Dose (RfDoa)(mg/kg-day)
7e-05
Oral Acute Reference Dose Reference
OPP
Oral Chronic Reference Dose (RfDoc) (mg/kg-day)
7e-05
Oral Chronic Reference Dose Reference
OPP

14.1.3 EPA Human Health Benchmarks for Pesticides

Chemical Substance
Acute or One Day PAD (RfD) [mg/kg/day]
0.00007
Acute or One Day HHBPs [ppb]
0.5
Acute HHBP Sensitive Lifestage/Population
Children
Chronic or One Day PAD (RfD) [mg/kg/day]
0.00007
Chronic or One Day HHBPs [ppb]
0.4
Chronic HHBP Sensitive Lifestage/Population
Females 13-49 yrs

14.1.4 Evidence for Carcinogenicity

Cancer Classification: Likely to be Carcinogenic to Humans (High Doses); Not Likely to be Carcinogenic to Humans (Low Doses)
USEPA Office of Pesticide Programs, Health Effects Division, Science Information Management Branch: "Chemicals Evaluated for Carcinogenic Potential" (April 2006)
No data are available in humans. Inadequate evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. S7 73 (1987)
A4; Not classifiable as a human carcinogen.
American Conference of Governmental Industrial Hygienists. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. ACGIH, Cincinnati, OH 2014, p. 59

14.1.5 Carcinogen Classification

1 of 2
IARC Carcinogenic Agent
Trichlorfon
IARC Carcinogenic Classes
Group 3: Not classifiable as to its carcinogenicity to humans
IARC Monographs

Volume 30: (1983) Miscellaneous Pesticides

Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

2 of 2
Carcinogen Classification
3, not classifiable as to its carcinogenicity to humans. (L135)

14.1.6 Health Effects

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.

14.1.7 Exposure Routes

The substance can be absorbed into the body by inhalation of its aerosol, through the skin and by ingestion.

14.1.8 Symptoms

Inhalation Exposure
Sweating. Nausea. Vomiting. Dizziness. Pupillary constriction, muscle cramp, excessive salivation. Laboured breathing. Convulsions. Unconsciousness. Symptoms may be delayed.
Skin Exposure
MAY BE ABSORBED! See Inhalation.
Eye Exposure
Redness. Pain. Pupillary constriction. Blurred vision.
Ingestion Exposure
Nausea. Vomiting. Weakness. Abdominal cramps. Diarrhoea. Pupillary constriction. Muscle cramps. Excessive salivation. Laboured breathing. Unconsciousness.
Symptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.

14.1.10 Adverse Effects

Neurotoxin - Predominantly motor

Other Poison - Organophosphate

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

ACGIH Carcinogen - Not Classifiable.

14.1.11 Acute Effects

14.1.12 Toxicity Data

LC50 (rat) = 533 mg/m3

14.1.13 Treatment

If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.

14.1.14 Interactions

The aim of this study is to determine the effect of levamisole and levamisole-trichlorfon combination on isolated sheep trachea. Contraction was achieved with levamisole concentrations (10(-8)-10(-3) M) on tracheal strips of adult sheep (> 1 year of age). Pretreatment with trichlorfon (10(-7) M)-levamisole (10(-7) M) decreased the pD2 and E(max) of Ach when compared to levamisole pretreatment (p < or = 0.01). Pretreatment with levamisole (10(-7) M), decreased the E(max) (p < or = 0.01) and pD2 (p < 0.05) of bethanechol concentrations (10(-8)-10(-3) M) significantly. Pretreatment with atropine (10(-6) M) decreased the E(max) of levamisole (10(-4) M) significantly (p < 0.05). To conclude, levamisole acted mainly on the muscarinic receptors of the sheep trachea and this effect was partly inhibited by atropine. Adverse interaction was present between levamisole and trichlorfon.
Baydan E et al; Pak J Biol Sci 11 (8): 1152-6 (2008)
In the forward mutation test system ade6 of the yeast Saccharomyces pombe, trichlorfon in combination with azinphos-methyl produced clearly synergistic effects for toxicity and mutagenicity. The addition of S9 microsomal liver fraction decreased the efficiency of single and combined treatments.
Gilot-Dehalle J et al; Mutat Res 117 (1-2): 139-48 (1983)
12 organophosphorus insecticides were tested for toxicity and mutagenicity in the forward mutation test system ade6 of the yeast Schizosaccharomyces pombe. EMS and MMS were selected as positive controls. 3 compounds, dichlorvos, trichlorfon and paraoxon, showed a linear dose-response relationship. Among the other compounds investigated, methyl derivatives, though in general more toxic than ethyl derivatives, did not significantly increase the mutation frequency. Trichlorfon, tested in combination with malathion, methylparathion or methylazinphos (guthion), produced clearly synergistic effects for both toxicity and mutagenicity. The addition of S9 microsomal liver fraction decreased the efficiency of both single and combined treatments only where a dose-response relationship or a synergistic effect was obtained.
Gilot-Dehalle J et al; Mutat Res 117 (1-2): 139-48 (1983)
Two randomized crossover studies were conducted to examine the effects of a combination of aluminum hydroxide (aluminium hydroxide) and magnesium hydroxide (Maalox TC), cimetidine, and ranitidine on the pharmacokinetics of trichlorfon (metrifonate) and its metabolite in a total of 34 healthy subjects (ages 45-75 yr) who received a single oral tablet of 50 mg trichlorfon alone, with or 90 min before a suspension of Maalox TC, or with or after pretreatment with oral tablets of 400 mg cimetidine or 150 mg ranitidine. The ratios and 90% confidence intervals (trichlorfon with comedication/trichlorfon alone) of AUC and Cmax of the drug and its metabolites fulfilled the criteria defined for showing lack of relevant interaction for all treatment comparisons in both studies. Trichlorfon was well tolerated.
Heinig R et al; Clin Drug Invest 17: 67-77 (1999)
For more Interactions (Complete) data for Trichlorfon (6 total), please visit the HSDB record page.

14.1.15 Antidote and Emergency Treatment

Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Organophosphates and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 294
Basic Treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway if needed). Suction if necessary. Aggressive airway control may be needed. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Organophosphates and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 294
Advanced Treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/ Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously and consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Administer atropine. Correct hypoxia before giving atropine ... . Administer pralidoxime chloride (2-PAM). UNDER DIRECT PHYSICIANS ORDER ... . Treat seizures with adequate atropinization and correction of hypoxia. In rare cases diazepam (Valium) or lorazepam (Ativan) may be necessary ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Organophosphates and related compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 294
Ensure that a clear airway exists. Intubate the patient and aspirate the secretions with a large bore suction device if necessary. Administer oxygen by mechanically assisted pulmonary ventilation if respiration is depressed and keep patient on a high FiO2. In severe poisonings, patients should be treated in an intensive care unit setting. /Organophosphate insecticides/
U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Roberts, J.R., Reigart, J.R. Recognition and Management of Pesticide Poisonings. 6th ed. 2013. EPA Document No. EPA 735K13001, and available in electronic format at: https://www2.epa.gov/pesticide-worker-safety, p. 47
For more Antidote and Emergency Treatment (Complete) data for Trichlorfon (22 total), please visit the HSDB record page.

14.1.16 Human Toxicity Excerpts

/SIGNS AND SYMPTOMS/ The muscarinic signs of /organophosphorus compounds/ ... consist of hypersalivation, lacrimation, sweating and nasal discharge. Miosis, dyspnea, vomiting, diarrhea and frequent urination also occur. The nicotinic effects consist of fasciculation of the muscles, weakness and paralysis. The central /nervous system/ effects include nervousness, apprehension, ataxia, convulsions and coma. Death is due to respiratory failure, or sometimes cardiac arrest. ... /Organophosphorus compounds/
Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988., p. 157
/SIGNS AND SYMPTOMS/ 1. Nausea is often the first symptom, followed by vomiting, abdominal cramps, diarrhea, and excessive salivation (sialorrhea). Hypothermia has been reported in animals and at least once in man as an early sign. 2. Headache, giddiness, vertigo, and weakness. 3. Rhinorrhea and a sensation of tightness in the chest are common in inhalation exposures. 4. Blurring or dimness of vision, miosis (with fixed pinpoint pupils), tearing, ciliary muscle spasm, loss of accommodation, and ocular pain. None of these eye effects are diagnostically dependable except in primary ocular exposures. Indeed, mydriasis is sometimes seen, probably due to sympatho-adrenal discharge. 5. Bradycardia or tachycardia. Varying degrees of AV heart block are described, as well as atrial arrhythmias. 6. Loss of muscle coordination, slurring of speech, fasciculations and twitching of muscles (particularly of the tongue and eyelids), and generalized profound weakness. 7. Mental confusion, disorientation, and drowsiness. 8. Difficulty in breathing, excessive secretion of saliva and of respiratory tract mucus, oronasal frothing, cyanosis, pulmonary rales and rhonchi, and hypertension presumably due to asphyxia). 9. Random jerky movements, incontinence, convulsions and coma. 10. Death primarily due to respiratory arrest arising from failure of the respiratory muscles, intense bronchoconstriction, or all three. /Parathion/
Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-340
/CASE REPORTS/ Five people exposed to high levels of Ditriphon 50, a Hungarian insecticide preparation containing trichlorfon as the active ingredient and unknown constituents /were studied/. /Results indicated/ an excess incidence of short lived chromosome breaks and exchange figures relative to karyotypes of 15 healthy volunteers matched for age only. A significant increase in stable chromosome alterations was also found among the people exposed to Ditriphon 50.
National Research Council. Drinking Water and Health, Volume 6. Washington, D.C.: National Academy Press, 1986., p. 399
/CASE REPORTS/ The characteristic clinical features of dipterex-induced delayed neurotoxicity in humans showed 3 stages: (1) acute encephalopathy, (2) followed by recovery without any residual symptoms, (3) followed by delayed neuropathy, 2-3 weeks later. All cases showed motor dominant polyneuropathy, but the most severe case developed myeloneuropathy. The histological evaluation of the sural nerve showed axonal change.
Shiraishi S et al; J Uoeh 5 (Suppl): 125-32 (1983)
For more Human Toxicity Excerpts (Complete) data for Trichlorfon (21 total), please visit the HSDB record page.

14.1.17 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ In rats given daily oral doses of 300 mg/kg body weight technical trichlorfon for 5 days, brain edema, congestion of organs, fatty degeneration, and glycogen depletion of the liver, glycogen depletion of the heart muscle and emphysema and local inflammation in the lungs were observed.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V30 215 (1983)
/LABORATORY ANIMALS: Acute Exposure/ Trichlorfon (200 mg/kg, orally) decreased blood acetylcholinesterase and pseudocholinesterase activities in dogs by up to approximately 3.5 and approximately 4 fold, respectively, within 0.5 hours of its administration.
Flores A et al; Arch Med Vet 14 (1): 23-7 (1982)
/LABORATORY ANIMALS: Acute Exposure/ When rats were given single oral doses of 10, 30, /or/ 100 mg/kg trichlorfon, the 100-mg/kg dose of trichlorfon caused salivation, tremor, diarrhea, ptosis, flat body, decreased body temperature, and decreased pentylenetetrazole seizure threshold, whereas the 30- or 10-mg/kg doses did not.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V7 927
/LABORATORY ANIMALS: Acute Exposure/ Acute toxicity tests were conducted to determine (a) the individual and interactive effects of water temperature (7, 12, 17 °C), pH (6.5, 7.5, 8.5, 9.5), and time on the toxicity of terbufos, trichlorfon, 4-nitrophenol, and 2,4-dinitrophenol to rainbow trout (Oncorhynchus mykiss) and the amphipod Gammarus pseudolimnaeus, and (b) the individual and interactive effects of water temperature and pH on chemical bioconcentration during acute tests with rainbow trout and Gammarus exposed to terbufos, 4-nitrophenol, and 2,4-dinitrophenol. The toxicity of all four chemicals was significantly affected by pH in all tests, except for Gammarus exposed to terbufos. The toxicity of terbufos to rainbow trout and Gammarus was less at pH 7.5 than at higher or lower pH. The toxicity of both nitrophenols decreased as pH increased, whereas the toxicity of trichlorfon increased with pH. The effect of pH on trichlorfon toxicity decreased with temperature. Temperature significantly affected the toxicity of all four chemicals to both species. Toxicity increased with temperature in all tests, except for rainbow trout exposed to nitrophenols; toxicity decreased as temperature increased for rainbow trout. Chemical bioconcentration was also significantly affected by temperature and pH and was directly related to toxicity in most tests. Significant interactive effects between toxicity-modifying factors were also frequently observed. Temperature and pH effects on chemical toxicity need to be considered in chemical hazard assessment to ensure adequate protection of aquatic organisms.
Howe GE et al; Environ Toxicol Chem 13 (1): 51-66 (1994)
For more Non-Human Toxicity Excerpts (Complete) data for Trichlorfon (78 total), please visit the HSDB record page.

14.1.18 Non-Human Toxicity Values

LD50 Rat (male and female) percutaneous >5000 mg/kg/24 hr
Tomlin CDS, ed. Trichlorfon (52-68-6). In: The e-Pesticide Manual, 13th Edition Version 3.2 (2005-06). Surrey UK, British Crop Protection Council.
LD50 Rat oral 250 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3529
LD50 Rat dermal 2000 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3529
LD50 Rat ip 160 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3529
For more Non-Human Toxicity Values (Complete) data for Trichlorfon (17 total), please visit the HSDB record page.

14.1.19 Ongoing Test Status

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of July 27, 2017: http://actor.epa.gov/dashboard/]
The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for trichlorfon is available.[Available from, as of May 24, 2017: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

14.2 Ecological Information

14.2.1 EPA Ecotoxicity

Pesticide Ecotoxicity Data from EPA

14.2.2 Ecotoxicity Values

LC50; Species: Gammarus fasciatus (/Scud/) mature; Conditions: static bioassay without aeration, 21 °C, pH 7.2-7.5, water hardness 40-50 mg/L as calcium carbonate and alkalinity of 30-35 mg/L; Concentration: 40 ug/L for 96 hr (95% confidence limit: 26-60 ug/L) /Technical material 98%/
U.S. Department of Interior, Fish and Wildlife Service. Handbook of Acute Toxicity of Chemicals to Fish and Aquatic Invertebrates. Resource Publication No. 137. Washington, DC: U.S. Government Printing Office, 1980., p. 78
LC50; Species: Procambarus (Crayfish) mature; Conditions: static bioassay without aeration, 12 °C, pH 7.2-7.5, water hardness 40-50 mg/L as calcium carbonate and alkalinity of 30-35 mg/L; Concentration: 7800 ug/L for 96 hr (95% confidence limit: 6520-9330 ug/L) /Technical material 98%/
U.S. Department of Interior, Fish and Wildlife Service. Handbook of Acute Toxicity of Chemicals to Fish and Aquatic Invertebrates. Resource Publication No. 137. Washington, DC: U.S. Government Printing Office, 1980., p. 78
LC50; Species: Pteronarcella badia (/Stonefly/) naiads; Conditions: static bioassay without aeration, pH 7.2-7.5, water hardness 40-50 mg/L as calcium carbonate and alkalinty of 30-35 mg/L; Concentration: 11 ug/L for 96 hr (95% confidence limit: 7.6-16 ug/L) /Technical material 98%/
U.S. Department of Interior, Fish and Wildlife Service. Handbook of Acute Toxicity of Chemicals to Fish and Aquatic Invertebrates. Resource Publication No. 137. Washington, DC: U.S. Government Printing Office, 1980., p. 78
LC50; Species: Pteronarcys california (/Stonefly/) second year class; Conditions: static bioassay without aeration, 16 °C, pH 7.2-7.5, water hardness 40-50 mg/L as calcium carbonate and alkalinity of 30-35 mg/L; Concentration: 35 ug/L/96 hr (95% confidence limit: 22-55 ug/L) /Technical material 98%/
U.S. Department of Interior, Fish and Wildlife Service. Handbook of Acute Toxicity of Chemicals to Fish and Aquatic Invertebrates. Resource Publication No. 137. Washington, DC: U.S. Government Printing Office, 1980., p. 78
For more Ecotoxicity Values (Complete) data for Trichlorfon (85 total), please visit the HSDB record page.

14.2.3 Ecotoxicity Excerpts

/BIRDS and MAMMALS/ Japanese quail /Coturnix japonica/ were given trichlorfon daily for 20 days at an oral dose of 5 mg/kg body weight. Hematological examinations were made on the 5th, 10th, 15th, and 20th day of treatment and on the 5th, 10th, 15th, and 30th day after stopping treatment. The number of erythrocytes dropped on the 5th and 10th days, and the values of the hematocrit and hemoglobin fell on the 5th day. A significant increase in erythroblast contents was found on the 5th and 10th day. No other significant changes of the above parameters were observed up to the 30th day after treatment. The numbers of leukocytes, lymphocytes, neutrophils, and monocytes sharply increased from the 5th to 15th day of treatment, and quikly dropped to normal ranges on the 10th day after stopping treatment.
WHO; Environ Health Criteria 132: Trichlorfon p. 49 (1992)
/AQUATIC SPECIES/ The cardio-respiratory function, oxidative stress and fish antioxidants were analyzed in juvenile Nile tilapia exposed for 96 hr to a sublethal trichlorfon concentration of 0.5 mg/L. The exposure to TRC induced oxidative stress in the heart, as manifested by the glutathione S-transferase depletion and hydroperoxide elevation, and was the most sensitive organ when compared to the liver and gills, in which the antioxidant mechanisms against TRC exposure were sufficient to remove reactive oxygen species (ROS), preventing the increase of lipid peroxidation. TRC exposure also reduced O(2) uptake (V O(2)) and increased the critical oxygen tension (PcO(2)), reducing the species capacity to survive prolonged hypoxic conditions. The heart rate and force contraction were significantly impaired, making the heart the most sensitive organ when exposed to the TRC.
Thomaz JM et al; Ecotoxicol Environ Saf 72 (5): 1413-24 (2009)
/AQUATIC SPECIES/ Trichlorfon (TCF) is one of the most used veterinary pharmaceuticals not only to fight infestations but also as a preventive measure worldwide. The high concentrations used generate concerns about environmental and human health. ...The acute toxicity of this compound to non-target organisms belonging to different trophic levels /was assessed/: Danio rerio (early life stages and adults), Daphnia magna and algae (Pseudokirchneriella subcapitata and Chlorella vulgaris), and studied the potential of the biomarkers cholinesterase (ChE), glutathione-S-transferase (GST), lactate dehydrogenase (LDH) and catalase (CAT) to assess sub-lethal effects of trichlorfon in zebrafish and daphnids. The fish embryo test followed the OECD draft guideline FET and was based on the exposure of newly fertilized eggs to 0, 2.5, 5.0, 10, 20, 40, 80 and 160 mg/L of TCF for 5 days; the fish acute test followed the OECD guideline 203 and was based on the exposure of adult fish to 0, 2.5, 5, 10, 20, 40, 60 and 80 mg/L of TCF for 4 days; Daphnia sp. immobilization assay followed the OECD guideline 202 and was based on the exposure of juvenile daphnids to 0, 0.1, 0.3, 0.5, 0.7, 0.9, 1 and 2 ug/L of TCF for 2 days and the algae growth inhibition assay followed the OECD guideline 201 and was based on the exposure of the two species to 0, 1, 3.2, 10, 32, 100 and 300 mg/L of TCF for 4 days. Biomarker levels were measured after 96 hr exposure to TCF in zebrafish early life stages and adults and after 48 hr exposure in D. magna. Tested organisms seem to have dissimilar sensitivities towards TCF exposure. D. magna (48 hr-LC(50)=0.29 ug/L) was the most sensitive organism, followed by early life stages and adults of zebrafish (96 hr-LC(50)=25.4 and 28.8 mg/L, respectively) and finally by the algae P. subcapitata (96 hr-LC(50)=274.5 mg/L) and C. vulgaris (no effect observed). As daphnids are a source of food for organisms of higher trophic levels, the impairment on its population is prone to have consequences in the entire ecosystem. The biomarker activities measured in daphnids and fish seemed to be useful tools in the assessment of trichlorfon effects, especially ChE activity which was the most sensitive biomarker tested for all organisms. Trichlorfon was teratogenic for zebrafish embryos leading to anomalies in the absorption of the yolk sac, spine bending and pericardial oedemas. The present research suggests that further work is urgently needed in order to monitor environmental concentrations of trichlorfon and to test the long term effects of environmentally realistic concentrations of this compound.
Coelho S et al; Aquat Toxicol 103 (3-4): 191-8 (2011)
/AQUATIC SPECIES/ Trichlorfon (TRC) is the most common organophosphorous insecticide used in aquaculture practices in Southeast Asian countries. Indiscriminate use of TRC can either damage or alter the enzymatic and hormonal activities in the living organisms. In this present study, therefore, toxicogenomic analyses using real time PCR was used to characterize expression levels of various genes in Pangasianodon hypophthalmus after exposure to three concentrations, the 96 hr 1/100(LC(50)) (0.01 mg/L), the 96 hr 1/10(LC(50)) (0.1 mg/L) and the 96 hr 1/2(LC(50)) (0.5 mg/L) of TRC for 6 hr, 24 hr, 96 hr, 7 days, 14 days, 28 days and 56 days respectively. The expression kinetics of stress and other cellular toxicity representative genes such as heat shock protein70 (HSP70), growth hormone, acetylcholinesterase (AChE), trypsinogen, cytochrome P4501B (CYP1B) and cytochrome oxidase subunit 1 (COI) were investigated in liver and gills. TRC at a level of 0.1 mg/L and 0.5 mg/L induced a time and dose-dependent increase in the expression of the HSP70, COI and CYPIB while the transcript level of AChE, growth hormone and trypsinogen were significantly down-regulated. These results could permit to develop a "molecular biomarker system" which can be applied as a first-tier method of identifying contaminant exposure before effects at population level occur.
Sinha AK et al; Comp Biochem Physiol Part D Genomics Proteomics 5 (3): 207-16 (2010)
For more Ecotoxicity Excerpts (Complete) data for Trichlorfon (23 total), please visit the HSDB record page.

14.2.4 ICSC Environmental Data

The substance is very toxic to aquatic organisms. This substance may be hazardous to the environment. Special attention should be given to bees and fish.

14.2.5 Environmental Fate / Exposure Summary

Trichlorfon's production and use as a veterinary medicine may result in its release to the environment through various waste streams; it's use as an insecticide will result in its direct release to the environment. If released to air, a vapor pressure of 7.8X10-6 mm Hg at 20 °C indicates trichlorfon will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase trichlorfon will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 2.5 days. Particulate-phase trichlorfon will be removed from the atmosphere by wet and dry deposition. Photodegradation of trichlorfon is slow and can result in the formation of another insecticide, dichlorvos. If released to soil, trichlorfon is expected to have high to very high mobility based upon reported Koc values of 6-79. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 2.2X10-11 atm-cu m/mole. Trichlorfon is not expected to volatilize from dry soil surfaces based upon its vapor pressure. The dissipation half-life for trichlorfon in soil is reported as <1-27 days. If released into water, trichlorfon may adsorb to suspended solids and sediment based upon the reported Koc values. Complete degradation of trichlorfon in aquatic environments occurs in <20 days. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's Henry's Law constant. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Trichlorfon is subject to hydrolysis with half-lives (22 °C) of 510 days (pH 4), 46 hours (pH 7), and <30 minutes (pH 9) being reported. Occupational exposure to trichlorfon may occur through inhalation and dermal contact with this compound at workplaces where trichlorfon is produced or used. Monitoring data indicate that the general population may be exposed to trichlorfon mainly via dermal contact where the pesticide is used, specifically at golf courses. Exposure can also occur through its medical administration. (SRC)

14.2.6 Natural Pollution Sources

Trichlorfon is not known to occur as a natural product.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V30: 210 (1983)

14.2.7 Artificial Pollution Sources

Trichlorfon's production and use as a veterinary anthelmintic medicine(1) may result in its release to the environment through various waste streams; it's use as an insecticide(1) will result in its direct release to the environment(SRC).
(1) Larranaga M et al; Hawley's Condensed Chemical Dictionary. 16th ed. Hoboken, NJ: John Wiley & Sons, Inc., p. 1364 (2016)

14.2.8 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 6-79(2-3) indicate that trichlorfon is expected to have high to very high mobility in soil(SRC). Volatilization of trichlorfon from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.2X10-11 atm-cu m/mole(SRC), based upon its vapor pressure, 7.8X10-6 mm Hg(4), and water solubility, 1.2X10+5 mg/L(5). Trichlorfon is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). Trichlorfon, at an initial concentration of 2 ppm in soil, degraded 100% in 1.5 months at pH values of 3-4.6 and in 0.5 months at pH values of 8.7-9.05(6). Half-lives in clay (pH 7.9) and calcerous (pH 8.1) soils have been determined to be 1.15 and 1.05 days, respectively(7). Persistence of trichlorfon in soils has been reported as 2 weeks or less and is degraded by ammonifying microorganisms(8). Trichlorfon degrades rapidly in aerobic soils with reported half-lives of approximately 1-27 days under non-sterile conditions(9). The dissipation half-life of trichlorfon from plants has been estimated to be 2.36-3.10 days(10).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Chu W, Chan K-H; Sci Total Environ 248: 1-10 (2000)
(3) Kawamoto K, Urano K; Chemosphere 19: 1223-31 (1989)
(4) Freed VH et al; Environ Health Perspect 20: 55-70 (1977)
(5) Wauchope RD et al; Rev Environ Contam Toxicol 123: 1-36 (1991)
(6) Kostovetskii Y et al; Vodn Resur 1: 167-72 (1976)
(7) Guirguis MW, Shafik MT; Bull Entomol Soc Egypt Econ Ser 8: 29-32 (1975)
(8) Verschueren K; Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. New York, NY: John Wiley & Sons (2001)
(9) Purdue University; National Pesticide Information Retrieval System (1987)
(10) Fantke P et al; Environ Sci Technol 48: 8588-602 (2014)
TERRESTRIAL FATE: The reported half-life for trichlorfon in aerobic soils was reported as 3-27 days. Using standard practices for application of pesticides to golf greens, trichlorfon dissipation half-lives were found to be 1.1 and 6 days in 1996 and 1997, respectively(1). Loss of trichlorfon due to volatilization, clipping removal and leaching from the greens was minimal(1). Dissipation of trichlorfon in individual components of the greens were as follows(1):
component
thatch
soil depth (cm)
0-2
organic carbon (%)
6.6
half-life (days)
1.0
component
mat
soil depth (cm)
2-5
organic carbon (%)
3.4
half-life (days)
7.7
component
soil layer;
soil depth (cm)
below 5
organic carbon (%)
0.3
half-life (days)
0.5
(1) Wu L et al; J Environ Qual 31: 889-895 (2002)
AQUATIC FATE: Based on a classification scheme(1), Koc values of 6-79(2-3) indicate that trichlorfon may adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 2.2X10-11 atm-cu m/mole(SRC), derived from its vapor pressure, 7.8X10-6 mm Hg(5), and water solubility, 1.2X10+5 mg/L(6). Trichlorfon is subject to hydrolysis and decomposition proceeds more rapidly with heating, and above pH 6(7). Hydrolysis half-lives (22 °C) of trichlorfon were reported as 510 days (pH 4), 46 hours (pH 7), and <30 minutes (pH 9)(7). According to a classification scheme(8), an estimated BCF of 3(SRC), from its log Kow of 0.51(9) and a regression-derived equation(10), suggests the potential for bioconcentration in aquatic organisms is low. Complete biodegradation of trichlorfon in river water occurred within 5 days at 10 mg/L, 13 days at 20 mg/L, and 20 days at 30 mg/L(11). In screening studies carried out at 20 °C using activated sludge inoculum, the aerobic biodegradation rate of trichlorfon was determined to be 0.28/day with a half-life of 2.5 days(12). Trichlorfon underwent photochemical conversion to dichlorvos when irradiated under UV light in an aqueous solution(13).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Chu W, Chan K-H; Sci Total Environ 248: 1-10 (2000)
(3) Kawamoto K, Urano K; Chemosphere 19: 1223-31 (1989)
(4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 15-1 to 15-29 (1990)
(5) Freed VH et al; Environ Health Perspect 20: 55-70 (1977)
(6) Wauchope RD et al; Rev Environ Contam Toxicol 123: 1-36 (1991)
(7) MacBean C, ed; e-Pesticide Manual. 15th ed., ver. 5.1, Alton, UK; British Crop Protection Council. Trichlorfon (52-68-6) (2008-2010)
(8) Franke C et al; Chemosphere 29: 1501-14 (1994)
(9) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 9 (1995)
(10) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of June 13, 2017: https://www2.epa.gov/tsca-screening-tools/
(11) Verschueren K; Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. New York, NY: John Wiley & Sons (2001)
(12) Kawamoto K, Urano K; Chemosphere 21: 1141-60 (1990)
(13) Floesser-Mueller H, Schwack W; Rev Environ Contam Toxicol 172: 129-228 (2001)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dichlorvos, which has a vapor pressure of 0.0158 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase dichlorvos is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals, ozone and nitrate radicals; the half-life for these reactions in air is estimated to be 11-19 hours, 70 days and 3.2 hours(SRC), calculated from respective rate constants of 2.0X10-11 to 3.5X10-11(3-5), 1.7X10-19(5) and 2.5X10-13(5) cu cm/molecule-sec. Dichlorvos absorbs light in the UV range with a maximum absorbance of 295-305 nm and was found to have a photodegradation rate constant of 2.652X10-9 L/sec, giving it a photodegradation half-life of about 7.25 hours(6).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) MacBean C, ed; e-Pesticide Manual. 15th ed., ver. 5.1, Alton, UK; British Crop Protection Council. Dichlorvos (62-73-7) (2008-2010)
(3) Sun F et al; Int J Chem Kinet 37: 755-62 (2005)
(4) Feigenbrugel V et al; Environ Sci Technol 40: 850-7 (2006)
(5) Aschmann SM et al; J Phys Chem A 115: 2756-64 (2011)
(6) Chen ZM et al; Ind Eng Chem Prod Res Dev 23: 5-11 (1984)

14.2.9 Environmental Biodegradation

AEROBIC: Complete biodegradation of trichlorfon in river water occurred within 5 days at 10 mg/L, 13 days at 20 mg/L, and 20 days at 30 mg/L(1). Persistence of trichlorfon in soils has been reported as 2 weeks or less and is degraded by ammonifying microorganisms(1). Trichlorfon degrades rapidly in aerobic soils with reported half-lives of approximately 1-27 days under non-sterile conditions(2). The biodegradation rate constant and half-life for trichlorfon was determined to be 0.28/day and 2.5 days, respectively, in an aerobic biodegradability test using an activated sludge inoculum incubated at 20 °C for 50 days(3). The decomposition rate of trichlorfon in river water at pH 7.39 was higher than in distilled water at pH 7.3-7.5 indicating that biodegradation aided in trichlorfon's decomposition in water(4).
(1) Verschueren K; Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. New York, NY: John Wiley & Sons (2001)
(2) Purdue University; National Pesticide Information Retrieval System (1987)
(3) Kawamoto K, Urano K; Chemosphere 21: 1141-60 (1990)
(4) Sobina NA et al; Mater Vses Simp Sovrem Probl Samoochishcheniya Regul Kach Vody 5th 3: 85-90 (1975)

14.2.10 Environmental Abiotic Degradation

The rate constant for the vapor-phase reaction of trichlorfon with photochemically-produced hydroxyl radicals has been estimated as 6.2X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.6 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Trichlorfon is subject to hydrolysis and decomposition proceeds more rapidly with heating, and above pH 6(2). Hydrolysis half-lives (22 °C) of trichlorfon were reported as 510 days (pH 4), 46 hours (pH 7), and <30 minutes (pH 9)(2). Trichlorfon is unstable under basic conditions and liberates hydrochloric acid in alkaline hydrolysis to form dichlorvos(3). Half-lives of 3.7 days, 6.5 hours and 63 minutes for trichlorfon have been reported in Sorensen buffers of pH 6, 7 and 8, respectively, at 37.5 °C(3). Trichlorfon slowly decomposes in aqueous acidic solutions(4). Trichlorfon was degraded to dichlorvos in water (99:1 water-ethanol) with half-lives of about 670, 67 and 17 hours at respective pH values of 6, 7 and 8(5). Photolysis of trichlorfon is slow(2). Trichlorfon underwent photochemical conversion to dichlorvos when irradiated under UV light in an aqueous solution(6).
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of June 13, 2017: https://www2.epa.gov/tsca-screening-tools
(2) MacBean C, ed; e-Pesticide Manual. 15th ed., ver. 5.1, Alton, UK; British Crop Protection Council. Trichlorfon (52-68-6) (2008-2010)
(3) Katagi T; Rev Environ Contam Toxicol 175: 79-261 (2002)
(4) Verschueren K; Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. New York, NY: John Wiley & Sons (2001)
(5) Chapman RA, Cole CM; J Environ Sci Health B17: 487-504 (1982)
(6) Floesser-Mueller H, Schwack W; Rev Environ Contam Toxicol 172: 129-228 (2001)

14.2.11 Environmental Bioconcentration

An estimated BCF of 3 was calculated in fish for trichlorfon(SRC), using a log Kow of 0.51(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low.
(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 9 (1995)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of June 13, 2017: https://www2.epa.gov/tsca-screening-tools/
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

14.2.12 Soil Adsorption / Mobility

The Koc of trichlorfon has been reported to be 6-79(1-6). According to a classification scheme(7), these Koc values suggests that trichlorfon is expected to have high to very high mobility in soil(SRC). In lysimeter studies designed to simulate golf course fairways and greens, trichlorfon was found to migrate quickly and was detected in the leachate after the first watering event(8).
(1) Chu W, Chan K-H; Sci Total Environ 248: 1-10 (2000)
(2) Dowd JF et al; Environ Toxicol Chem 12: 429-39 (1993)
(3) Petrovic AM et al; Chemosphere 27: 1272-7 (1993)
(4) Lohniger H; Chemosphere 29: 1611-26 (1994)
(5) Sabljic A et al; Chemosphere 31: 4489-514 (1995)
(6) Kawamoto K, Urano K; Chemosphere 19: 1223-31 (1989)
(7) Swann RL et al; Res Rev 85: 17-28 (1983)
(8) Odanaka Y et al; J Pesticide Sci 19: 1-10 (1994)

14.2.13 Volatilization from Water / Soil

The Henry's Law constant for trichlorfon is estimated as 2.2X10-11 atm-cu m/mole(SRC) derived from its vapor pressure, 7.8X10-6 mm Hg(1), and water solubility, 1.2X10+5 mg/L(2). This Henry's Law constant indicates that trichlorfon is expected to be essentially nonvolatile from water and moist soil surfaces(3). Trichlorfon is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1). In a study of a creeping bentgrass putting green under customary field management practices at the University of California-Riverside Turf Research Facility conducted in 1996 and 1997, the cumulative loss of trichlorfon due to volatilization was only 0.01 and 0.008% of applied mass, respectively(4).
(1) Freed VH et al; Environ Health Perspect 20: 55-70 (1977)
(2) Wauchope RD et al; Rev Environ Contam Toxicol 123: 1-36 (1991)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)
(4) Wu L et al; J Environ Qual 31: 889-895 (2002)

14.2.14 Environmental Water Concentrations

SURFACE WATER: The highest concentration of trichlorfon in water samples taken downstream from a pesticide factory in Hunan, China was 4 ppm(1). Trichlorfon was detected at 14 of 22 sampling sites collected 1989-1990 in the Guadalquivir River Basin, Spain at mean concentrations of 0.01-2.18 ug/L(2). Trichlorfon was detected in 18 surface water samples collected from two vineyard catchments in southwestern Germany at concentrations of 6-182 ug/L after aerial application(3). Trichlorfon was detected in water samples collected Sep 2008 to Mar 2009 from 24 stream systems in southeast Australia at 0.002-0.006 ug/L(4).
(1) Niu X, Liu S; Huanjing Kexue 6: 45-9 (1985)
(2) Espigares M et al; Environ Toxicol Water Qual 12: 249-56 (1997)
(3) Schulz R; J Environ Qual 33: 419-48 (2004)
(4) Schafer RB et al; Environ Sci Technol 45: 1665-72 (2011)

14.2.15 Sediment / Soil Concentrations

SEDIMENT: Trichlorfon was not detected (detection limit 2.0 ug/kg) in sediment samples collected Sep 2008 to Mar 2009 from 24 stream systems in southeast Australia(1).
(1) Schafer RB et al; Environ Sci Technol 45: 1665-72 (2011)

14.2.16 Atmospheric Concentrations

SOURCE DOMINATED: Average daily ambient concentration of trichlorfon were 1.1X10-3, 1.7X10-3 and 1.5X10-3 ng/cu m over golf courses in Boston, MA, Philadelphia, PA and Rochester, NY, respectively(1). Maximum concentrations of trichlorfon over the same golf courses were 5.1X10-2, 8.1X10-2 and 7.0X10-2 ug/cu m, respectively(1).
(1) Murphy RR, Haith DA; Environ Sci Technol 41: 1038-43 (2007)

14.2.17 Food Survey Values

Trichlorfon was detected in 1 of 13,980 food samples collected by state food laboratories in 10 states (California, Florida, Indiana, Massachusetts, Michigan, New York, North Carolina, Oregon, Virginia, Wisconsin) during fiscal year 1988; it was not detected in 13,085 food samples collected during a similar study conducted in fiscal year 1989(1). In a study of grapes, 60% of trichlorfon residues were found in the skin; levels were higher in grape juice concentrate, raisins, and wine than in grapes, and trichlorfon accumulated in wine(2). Trichlorfon applied as a veterinary medicine can produce residues in meat(3). Trichlorfon was not detected (detection limit 9.35 ng/g) in 278 honey samples collected in 2003-2004 from 33 locations throughout Turkey(4).
(1) Minyard JP, Roberts WE; J Assoc Off Anal Chem 74: 438-52 (1991)
(2) IARC; IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans 30: 207-31 (1983)
(3) Humphreys DJ; Veterinary Toxicology 3rd ed, London, England: Bailliere, Tindell (1988)
(4) Das YK, Kaya S; Bull Environ Contam Toxicol 83: 78-83 (2009)
Trichlorfon was not detected in the following food products(1-4):
Commodity
olive oil
Detection Limit (ug/kg)
0.9
Location
south Spain
Reference
1
Commodity
rapeseed
Detection Limit (ug/kg)
5
Location
China
Reference
2
Commodity
rapeseed oil
Detection Limit (ug/kg)
10
Location
China
Reference
2
Commodity
rapeseed meal
Detection Limit (ug/kg)
6
Location
China
Reference
2
Commodity
commercial tea
Detection Limit (ug/kg)
78
Location
not reported
Reference
3
Commodity
ginseng
Detection Limit (ug/kg)
78
Location
not reported
Reference
3
Commodity
leek
Detection Limit (ug/kg)
3.3
Location
Beijing China
Reference
4
(1) Garrido Frenich A et al; J Agric Food Chem 55: 8346-52 (2007)
(2) Jiang Y et al; J Agric Food Chem 60: 5089-98 (2012)
(3) Chen Y et al; J Agric Food Chem 64: 6125-32 (2016)
(4) Zou N et al; J Agric Food Chem 64: 6061-70 (2016)

14.2.18 Plant Concentrations

Trichlorfon was detected at 0.05 ppm in seeds harvested from plants treated with twice the registered rate of foliar spray application, it was not detected (detection limit 0.02 ppm) in alfalfa plants germinated from those seeds(1). Trichlorfon was not detected (detection limit not reported) in 8 tomato, 12 cucumber or 4 onion samples from Cuba, but was detected at 0.08-0.12 ug/kg in 12 pepper crop samples(2).
(1) Maitlen JC, Halfhill JE; J Agric Food Chem 33: 754-7 (1985)
(2) Dierksmeier G et al; pp 400-24 in Pesticide Residues in Coastal Tropical Ecosystems. Taylor MD et al, eds. Boca Raton, FL: CRC Press (2003

14.2.19 Fish / Seafood Concentrations

Trichlorfon was not detected (detection limit 0.05 mg/kg) in Australian farmed yellowtail kingfish (Seriola lalandi) or Mulloway (Argyrosomus hololepidotus); fish were collected Sept 2003 to July 2004(1).
(1) Padula DJ et al; Chemosphere 86: 709-17 (2012)

14.2.20 Animal Concentrations

Trichlorfon was not detected in the liver tissue of 23 food-producing animals in 1980(1). Trichlorfon was not detected (detection limit 0.2 mg/kg) in four raw wool samples(2).
(1) IARC; Miscellaneous Pesticides. 30: 207-31 (1983) Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available, from, as of Jun 1, 2017: https://monographs.iarc.fr/ENG/Classification/index.php
(2) Niell S et al; J Agric Food Chem 59: 7601-8 (2011)

14.2.21 Milk Concentrations

Following dermal and intragastric application of trichlorfon to cows, the parent compound and dichlorvos were detected in the milk up to 22 days after application(1).
(1) IARC; Miscellaneous Pesticides. 30: 207-31 (1983) Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available, from, as of Jun 1, 2017: https://monographs.iarc.fr/ENG/Classification/index.php

14.2.22 Other Environmental Concentrations

Samples of tobacco leaf collected 1976-1977 from cured commercial crops in three warehouses in Ontario, Canada did not contain trichlorfon(1). Trichlorfon was not detected in cured tobacco samples collected 1976-1978 from 33-34 farms in southern Ontario even though fields had been treated with the chemical(1). Trichlorfon was not detected (detection limit 10 ug/kg) in 118 tobacco samples from China(2). Trichlorfon is listed as an ingredient in two home use products(3).
(1) IARC; Miscellaneous Pesticides. 30: 207-31 (1983) Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available, from, as of Jun 1, 2017: https://monographs.iarc.fr/ENG/Classification/index.php
(2) Chen X et al; J Agric Food Chem 61:5746-57 (2013)
(3) National Library of Medicine Household Products Database. Available from, as of June13, 2017: https://hpd.nlm.nih.gov/

14.2.23 Probable Routes of Human Exposure

NIOSH (NOES Survey 1981-1983) has statistically estimated that 338 workers (131 of these are female) were potentially exposed to trichlorfon in the US(1). The NOES Survey does not include farm workers. Occupational exposure to trichlorfon may occur through inhalation and dermal contact with this compound at workplaces where trichlorfon is produced or used(SRC). During vineyard spraying operations, the operator's hands in the cab (with no air-conditioning) of a spray tractor are potentially exposed to 56.16 ug/100 sq cm trichlorfon via dermal contact with contaminated surfaces of the cab(2). In pesticide formulating plants, exposure to trichlorfon may be from spillage; there is a high potential for exposure at mixing and bagging stations(3). Trichlorfon is applied to several crops and forests via aerial or ground spraying (2,4-5) and contaminated equipment may be a potential source of dermal exposure of operators to trichlorfon(2). Crop workers may be exposed during application, however, their main exposure results from contact with treated foliage or to pesticide or pesticide-contaminated material made airborne through agitation of foliage during work activity(3-4). Incidental to treating a crop, some pesticides, such as trichlorfon, may drift onto workers in neighboring fields or in nearby suburban areas without there being any intent to treat those areas(3,5). Monitoring data indicate that the general population may be exposed to trichlorfon mainly via dermal contact where the pesticide is used, specifically at golf courses(SRC). Exposure can also occur through its medical administration(SRC).
(1) NIOSH; National Occupational Exposure Survey (1983)
(2) Yoshida K et al; J Environ Sci Health B25: 169-83 (1990)
(3) Wolfe HR; pp. 137-63 in Air Pollut Pest & Agric Processes. Lee RI Jr, ed., Boca Raton, FL: CRC Press (1976)
(4) Iwata Y et al; J Agric Food Chem 27: 1141-5 (1979)
(5) IARC; Miscellaneous Pesticides. 30: 207-31 (1983) Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available, from, as of Jun 1, 2017: https://monographs.iarc.fr/ENG/Classification/index.php

14.2.24 Average Daily Intake

A Chinese total diet study, conducted in 1990, found that the average daily intake of trichlorfon was 0, 0, 0 and 11.5 ug/person/day in 4 different regions(1).
(1) Chen J, Gao J; J AOAC Int 76: 1193-1205 (1993)

15 Associated Disorders and Diseases

Associated Occupational Diseases with Exposure to the Compound

16 Literature

16.1 Consolidated References

16.2 NLM Curated PubMed Citations

16.3 Springer Nature References

16.4 Chemical Co-Occurrences in Literature

16.5 Chemical-Gene Co-Occurrences in Literature

16.6 Chemical-Disease Co-Occurrences in Literature

17 Patents

17.1 Depositor-Supplied Patent Identifiers

17.2 WIPO PATENTSCOPE

17.3 Chemical Co-Occurrences in Patents

17.4 Chemical-Disease Co-Occurrences in Patents

17.5 Chemical-Gene Co-Occurrences in Patents

18 Interactions and Pathways

18.1 Chemical-Target Interactions

18.2 Drug-Drug Interactions

19 Biological Test Results

19.1 BioAssay Results

20 Classification

20.1 MeSH Tree

20.2 NCI Thesaurus Tree

20.3 ChEBI Ontology

20.4 KEGG: Pesticides

20.5 KEGG: ATC

20.6 KEGG: Risk Category of Japanese OTC Drugs

20.7 KEGG: OTC drugs

20.8 KEGG: Animal Drugs

20.9 KEGG: Drug Groups

20.10 KEGG : Antimicrobials

20.11 WHO ATC Classification System

20.12 ChemIDplus

20.13 CAMEO Chemicals

20.14 ChEMBL Target Tree

20.15 UN GHS Classification

20.16 EPA CPDat Classification

20.17 NORMAN Suspect List Exchange Classification

20.18 CCSBase Classification

20.19 EPA DSSTox Classification

20.20 International Agency for Research on Cancer (IARC) Classification

20.21 Consumer Product Information Database Classification

20.22 EPA Substance Registry Services Tree

20.23 MolGenie Organic Chemistry Ontology

21 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    Phosphonic acid, P-(2,2,2-trichloro-1-hydroxyethyl)-, dimethyl ester
    https://services.industrialchemicals.gov.au/search-assessments/
    Phosphonic acid, P-(2,2,2-trichloro-1-hydroxyethyl)-, dimethyl ester
    https://services.industrialchemicals.gov.au/search-inventory/
  2. CAMEO Chemicals
    LICENSE
    CAMEO Chemicals and all other CAMEO products are available at no charge to those organizations and individuals (recipients) responsible for the safe handling of chemicals. However, some of the chemical data itself is subject to the copyright restrictions of the companies or organizations that provided the data.
    https://cameochemicals.noaa.gov/help/reference/terms_and_conditions.htm?d_f=false
    CAMEO Chemical Reactivity Classification
    https://cameochemicals.noaa.gov/browse/react
  3. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  4. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  5. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  6. DTP/NCI
    LICENSE
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    https://www.cancer.gov/policies/copyright-reuse
  7. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  8. EPA Safe Drinking Water Act (SDWA)
  9. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
  10. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  11. Hazardous Substances Data Bank (HSDB)
  12. ILO-WHO International Chemical Safety Cards (ICSCs)
  13. New Zealand Environmental Protection Authority (EPA)
    LICENSE
    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  14. NJDOH RTK Hazardous Substance List
  15. Occupational Safety and Health Administration (OSHA)
    LICENSE
    Materials created by the federal government are generally part of the public domain and may be used, reproduced and distributed without permission. Therefore, content on this website which is in the public domain may be used without the prior permission of the U.S. Department of Labor (DOL). Warning: Some content - including both images and text - may be the copyrighted property of others and used by the DOL under a license.
    https://www.dol.gov/general/aboutdol/copyright
  16. Risk Assessment Information System (RAIS)
    LICENSE
    This work has been sponsored by the U.S. Department of Energy (DOE), Office of Environmental Management, Oak Ridge Operations (ORO) Office through a joint collaboration between United Cleanup Oak Ridge LLC (UCOR), Oak Ridge National Laboratory (ORNL), and The University of Tennessee, Ecology and Evolutionary Biology, The Institute for Environmental Modeling (TIEM). All rights reserved.
    https://rais.ornl.gov/
  17. EU Pesticides Database
  18. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
    LICENSE
    Copyright (c) 2022 Haz-Map(R). All rights reserved. Unless otherwise indicated, all materials from Haz-Map are copyrighted by Haz-Map(R). No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
    https://haz-map.com/About
  19. ChEBI
  20. NCI Thesaurus (NCIt)
    LICENSE
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    https://www.cancer.gov/policies/copyright-reuse
  21. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  22. Toxin and Toxin Target Database (T3DB)
    LICENSE
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    http://www.t3db.ca/downloads
  23. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  24. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    trichlorfon
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  25. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  26. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  27. Consumer Product Information Database (CPID)
    LICENSE
    Copyright (c) 2024 DeLima Associates. All rights reserved. Unless otherwise indicated, all materials from CPID are copyrighted by DeLima Associates. No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
    https://www.whatsinproducts.com/contents/view/1/6
    Consumer Products Category Classification
    https://www.whatsinproducts.com/
  28. EPA Chemical and Products Database (CPDat)
  29. EPA Pesticide Ecotoxicity Database
  30. USDA Pesticide Data Program
  31. Hazardous Chemical Information System (HCIS), Safe Work Australia
  32. NITE-CMC
    Dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate; Trichlorfon; DEP - FY2006 (New/original classication)
    https://www.chem-info.nite.go.jp/chem/english/ghs/06-imcg-0274e.html
    Dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate [tichlorfon or DEP] - FY2015 (Revised classification)
    https://www.chem-info.nite.go.jp/chem/english/ghs/15-mhlw-0034e.html
  33. FDA Approved Animal Drug Products (Green Book)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  34. Joint FAO/WHO Expert Committee on Food Additives (JECFA)
    LICENSE
    Permission from WHO is not required for the use of WHO materials issued under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Intergovernmental Organization (CC BY-NC-SA 3.0 IGO) licence.
    https://www.who.int/about/policies/publishing/copyright
  35. USGS Columbia Environmental Research Center
  36. Human Metabolome Database (HMDB)
    LICENSE
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    http://www.hmdb.ca/citing
  37. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  38. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
  39. SpectraBase
    DIMETHYL 1-HYDROXY-2,2,2-TRICHLOROETHYLPHOSPHONATE
    https://spectrabase.com/spectrum/GB5bAbVs2ts
  40. International Agency for Research on Cancer (IARC)
    LICENSE
    Materials made available by IARC/WHO enjoy copyright protection under the Berne Convention for the Protection of Literature and Artistic Works, under other international conventions, and under national laws on copyright and neighbouring rights. IARC exercises copyright over its Materials to make sure that they are used in accordance with the Agency's principles. All rights are reserved.
    https://publications.iarc.fr/Terms-Of-Use
    IARC Classification
    https://www.iarc.fr/
  41. Japan Chemical Substance Dictionary (Nikkaji)
  42. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Risk category of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08312.keg
    Classification of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08313.keg
  43. MassBank Europe
  44. Metabolomics Workbench
  45. NMRShiftDB
  46. Springer Nature
  47. SpringerMaterials
    dimethyl (2,2,2-trichloro-1-hydroxyethyl)phosphonate
    https://materials.springer.com/substanceprofile/docs/smsid_ukuhffokjxlaviqm
  48. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
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    https://www.whocc.no/copyright_disclaimer/
  49. Wikidata
  50. Wikipedia
  51. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
  52. PubChem
  53. GHS Classification (UNECE)
  54. EPA Substance Registry Services
  55. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  56. PATENTSCOPE (WIPO)
  57. NCBI
CONTENTS