National Toxicology Program

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. ¹

Names (NTP)

• 2-Chloroethyltrimethylammonium chloride
• 2-CHLORO-N,N,N-TRIMETHYL-ETHANAMINIUM CHLORIDE (9CI)
• CHLOROCHOLINE CHLORIDE

Human Toxicity Excerpts

• Discussion of a case of acute contact dermatitis caused by occupational exposure to the growth inhibitor cycocel. [Fischer T; Contact Dermatitis 10 (5): 316-7 (1984)]**PEER REVIEWED**
  
• A case was provided of accidental ingestion of Cycocel which manifested as a cholinergic crisis that led to sudden death. The patient was a 59 yr old male nursery worker who accidentally drank a mouthful of plant growth chemical Cycocel, containing the active ingredient (2-chloroethyl)trimethylammonium chloride (chlormequat). Initially he was seen by his family physician and indicated he had not swallowed any of the liquid. He later realized that he must have swallowed some of the liquid. An electrocardiogram revealed-T wave inversion and flat AVF. Following transfer to the hospital, the patient suffered a seizure, demonstrated bradycardia, experienced severe dysrhythmia followed by ventricular fibrillation which eventually resulted in asystole. Autopsy results indicated marked pulmonary edema, coronary atherosclerosis, atheromata of aorta, and localized adenocarcinoma of the prostate. Chlormequat was detected in the stomach contents and urine. The Cycocel the patient ingested apparently was kept in a refrigerator at the nursery along with bottled drinking water. The appearance of these solutions is similar; however, the cycocel has a fishy smell. [Winek CL et al; J Anal Toxicol 14 (4): 257-8 (1990)]**PEER REVIEWED**
  

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Non-Human Toxicity Excerpts

• RATS OF EACH SEX WERE ADMIN EITHER 1500 OR 3000 PPM IN FEED FOR 108 WK, & MICE WERE ADMIN 500 OR 2000 PPM IN FEED FOR 102 WK. NO TUMORS OCCURRED IN RATS OR MICE OF EITHER SEX. [CARCINOG TEST PROGRAM, BETHESDA; BIOASSAY OF (2-CHLOROETHYL) TRIMETHYLAMMONIUM CHLORIDE (CCC) FOR POSSIBLE CARCINOGENICITY; REPORT: 103 PAGES (1979) DHEW/PUB/NIH-79-1714, NCI-CG-TR-158; ORDER NO PB-293627]**PEER REVIEWED**
  
• In mallards: signs of intoxication: Ataxia, miosis, falling, sitting, using wings for pedestrian locomotion, tremors, tetanic seizures, immobility, opisthotonos, and frequent spasms. Signs appeared as soon as 5 min and mortalities usually occurred between 15 and 40 min after /oral/ treatment. Remission took up to 3 days. [U.S. Department of the Interior, Fish and Wildlife Service. Handbook of Toxicity of Pesticides to Wildlife. Resource Publication 153. Washington, DC: U.S. Government Printing Office, 1984., p. 22]**PEER REVIEWED**
  
• Non-toxic to fish. Not toxic to bees. [Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987., p. A082/Aug 87]**PEER REVIEWED**
  
• Researchers investigated the effects of CCC on the ability of deer mice (Peromyscus maniculatus) to resist challenge with a sublethal dose of Venezuelan equine encephalitis virus. CCC was continuously delivered in low doses in the feed at 1, 10, 20 or 40 mg/kg body wt/day. CCC had no effect on viremia duration or titer except when given in doses of 1 mg/kg body wt/day when it significantly (P less than or equal to 0.05) decr mean viremia titers compared to controls. Early antibody responses were incr by CCC treatment except in the 10 mg/kg body wt/day treatment group in which titers were decreased. By 30 days post inoculation antibody titers of CCC-treated mice were no different from controls. [Fairbrother A et al; Toxicology 31 (1): 67-71 (1984)]**PEER REVIEWED**
  
• Acutely toxic doses of CCC cause lacrimation, salivation, and intestinal motility, and although these signs of toxicity of CCC in mammals resemble those of anticholinesterase agents, the chemical does not inhibit cholinesterase. These effects are produced by stimulation at muscarinic receptors and are partially antagonized by low doses of atropine, a cholinergic blocking agent which specifically blocks muscarinic receptors. Lethal doses cause respiratory failure that is due to neuromuscular blockage and that is unaffected by atropine treatment. [DHEW/NCI; Bioassay of (2-Chloroethyl) Trimethylammonium chloride (CCC) for Possible Carcinogenicity p.2 (1979) Technical Rpt Series No. 158 DHEW Pub No. (NIH)79-1714]**PEER REVIEWED**
  
• 500 mg/kg of (2-Chloroethyl)trimethylammonium chloride given orally killed 21/40 male mice. [DHEW/NCI; Bioassay of (2-Chloroethyl)trimethylammonium chloride for Possible Carcinogenicity p. 1 (1979) Technical Rpt Series No. 158 NIH Pub No. 79-1714]**PEER REVIEWED**
  
• ... Plant growth regulator which influences the habit of certain plants by shortening and strengthening the stem ... . It can also influence the developmental cycle resulting in increased flowering and harvest. [Worthing, C.R. and S.B. Walker (eds.). The Pesticide Manual - A World Compendium. 8th ed. Thornton Heath, UK: The British Crop Protection Council, 1987., p. 158]**PEER REVIEWED**
  
• Cycocel was found to be negative when tested for mutagenicity using the Salmonella/microsome preincubation assay. This reference reports on the testing of 270 chemicals, including cycocel, using the standard protocol approved by the National Toxicology Program (NTP). The tests were performed by one or more of 3 different laboratories under contract to NTP. This test procedure includes testing of the chemical using a wide range of doses in as many as 5 Salmonella typhimurium strains (TA1535, TA1537, TA97, TA98, and TA100) in the presence and absence of rat and hamster liver S-9. Cycocel was tested at doses of 0.100, 0.333, 1.000, 3.333, and 10.000 mg/plate. The highest ineffective dose tested in any S.typhimurium strain was 10.000 mg/plate. [Mortelmans K et al; Environ Mutagen 8:1-119 (1986)]**PEER REVIEWED**
  

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Human Toxicity Values

• None found

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Non-Human Toxicity Values

• LD50 Rat oral 330-750 mg/kg. [DHEW/NCI; Bioassay of (2-Chloroethyl)trimethylammonium chloride for Possible Carcinogenicity p. 1 (1979) Technical Rpt Series No. 158 NIH Pub No. 79-1714]**PEER REVIEWED**
  
• LD50 Mouse oral 215-1020 mg/kg [DHEW/NCI; Bioassay of (2-Chloroethyl)trimethylammonium chloride for Possible Carcinogenicity p. 1 (1979) Technical Rpt Series No. 158 NIH Pub No. 79-1714]**PEER REVIEWED**
  
• LD50 Rat percutaneous >4000 mg/kg [Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987., p. A082/Aug 87]**PEER REVIEWED**
  
• LD50 Rabbit male percutaneous 440 mg/kg [Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987., p. A082/Aug 87]**PEER REVIEWED**
  
• LC50 Rat inhalation >5.2 mg/l/4 hr [Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987., p. A082/Aug 87]**PEER REVIEWED**
  

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Absorption, Distribution and Excretion

• In mammals, following oral administration, 97% is eliminated within 24 hr, principally as the unchanged substance. [Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987., p. A082/Aug 87]**PEER REVIEWED**
  

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Metabolism/Metabolites

• When (14)C-labeled CCC was applied to kohlrabi, cauliflower, or tomatoes, degradation of CCC was very small. The first product was probably choline which entered the plant pool. Small amounts of labeled methyl groups from choline were found as S-methyl methionine. CCC was not degraded when applied to sugarcane. Inalfalfa, CCC was slowly metabolized and was primarily incorporated into choline of phosphatidylcholine. [Menzie, C.M. Metabolism of Pesticides-Update III. Special Scientific Report- Wildlife No. 232. Washington, DC: U.S.Department of the Interior, Fish and Wildlife Service, 1980., p. 115]**PEER REVIEWED**
  
• Almond seedlings were treated with labeled CCC. Translocation to leaves and to the roots was observed. (14)CO2 was formed within 2 h after application. Radioactivity was observed in 17 known amino acids, an unidentified ninhydrin positive compound, malic acid, citric acid, choline and 2-chloroethylamine. [Menzie, C.M. Metabolism of Pesticides-Update III. Special Scientific Report- Wildlife No. 232. Washington, DC: U.S.Department of the Interior, Fish and Wildlife Service, 1980., p. 115]**PEER REVIEWED**
  
• When CCC was incubated in rumen contents or juice under anaerobic conditions, microbial degradation of CCC did not occur. [Menzie, C.M. Metabolism of Pesticides-Update III. Special Scientific Report- Wildlife No. 232. Washington, DC: U.S.Department of the Interior, Fish and Wildlife Service, 1980., p. 115]**PEER REVIEWED**
  
• (14)CH3 CCC was metabolized to choline in barley, wheat, tobacco and maize. Choline isolated from these plants containea 10-20% of the applied radioactivity. A small part of the radioactivity was also found in the betaine fraction. In Nicotiana rustica, methyl groups of (14)CH3 CCC were incorporated into the alkaloid nicotine; in Hordeum vulgare, into the alkaloid gramine. Radioactivity from l,2-(14)C CCC was also found in the choline moiety of phosphatidyl choline in winter barley (Hordeum vulgare variety Dover). [Menzie, C.M. Metabolism of Pesticides, Update II. U.S. Department of the Interior, Fish Wildlife Service, Special Scientific Report - Wildlife No. 2l2. Washington, DC: U.S. Government Printing Office, 1978., p. 75]**PEER REVIEWED**
  
• When applied to coastal bermudagrass, l,2-(14)C CCC was metabolized; and, within24 to 48 hr after application, about 25% of the label was found distributed among choline, betaine hydrochloride, serine, ethanolamine, glucose and CO2. [Menzie, C.M. Metabolism of Pesticides, Update II. U.S. Department of the Interior, Fish Wildlife Service, Special Scientific Report - Wildlife No. 2l2. Washington, DC: U.S. Government Printing Office, 1978., p. 75]**PEER REVIEWED**
  
• Wheat seedlings were root-treated with 1,2-(14)C chlormequat. Translocation was rapid and choline was formed. The latter was metabolized via betaine, which was demethylated, to glycine and serine. These were then incorporated into the plant protein fractions. Some (14)CO2 was also formed. [Menzie, C.M. Metabolism of Pesticides, Update II. U.S. Department of the Interior, Fish Wildlife Service, Special Scientific Report - Wildlife No. 2l2. Washington, DC: U.S. Government Printing Office, 1978., p. 75]**PEER REVIEWED**
  

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TSCA Test Submissions

• None found

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Footnotes

¹ Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.