Oral toxicity of 1,1-dichloroethylene in the rat: effects of sex, age, and fasting. 1977

M E Andersen, and L J Jenkins

Mortality curves for groups of fasted male rats treated with single, oral doses of 1,1-dichloroethylene (1,1-DCE, vinylidene chloride) were not monotonically increasing sigmoids, but were complex with maxima or extended plateaus in the region of dose between 100 and 700 mg of 1,1-DCE/kg. The exact shape was a function of the size (age) of the rat used. When groups of rats of various sizes were dosed with 50 mg/kg, mortality and hepatotoxicity were greatest for those groups whose average weight was between 100 and 150 g. Smaller and larger male rats were less susceptible to 1,1-DCE intoxication. The toxicity of 1,1-DCE was less severe in female rats and there was no significant effect of rat size on 1,1-DCE toxicity in females. In rats of both sexes the dose dependence of the hepatotoxic response was complex, possessing a threshold level, a region of precipitous increase, and a plateau, where larger doses were ineffective in increasing hepatotoxicity. The threshold in male rats of 100-150 g occurred near 50 mg/kg, and for females it was closer to 100 mg/kg. Considered in their entirety these data suggest that 1,1-DCE is metabolized to a toxic intermediate via some saturable pathway. Based on the effects of pretreatment with microsomal enzyme inhibitors and activators on 1,1-DCE toxicity in rats of various sizes, it appears that there are at least two microsomal reactions involved in 1,1-DCE metabolism.

UI MeSH Term Description Entries
D007064 L-Iditol 2-Dehydrogenase An alcohol oxidoreductase which catalyzes the oxidation of L-iditol to L-sorbose in the presence of NAD. It also acts on D-glucitol to form D-fructose. It also acts on other closely related sugar alcohols to form the corresponding sugar. EC 1.1.1.14 Iditol Dehydrogenase,Sorbitol Dehydrogenase,Polyol Dehydrogenase,2-Dehydrogenase, L-Iditol,Dehydrogenase, Iditol,Dehydrogenase, Polyol,Dehydrogenase, Sorbitol,L Iditol 2 Dehydrogenase
D007770 L-Lactate Dehydrogenase A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist. Lactate Dehydrogenase,Dehydrogenase, L-Lactate,Dehydrogenase, Lactate,L Lactate Dehydrogenase
D007928 Lethal Dose 50 The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population. LD50,Dose 50, Lethal
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D004000 Dichloroethylenes Toxic chlorinated unsaturated hydrocarbons. Include both the 1,1- and 1,2-dichloro isomers. Both isomers are toxic, but 1,1-dichloroethylene is the more potent CNS depressant and hepatotoxin. It is used in the manufacture of thermoplastic polymers. Vinylidene Chlorides,Chlorides, Vinylidene
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005215 Fasting Abstaining from FOOD. Hunger Strike,Hunger Strikes,Strike, Hunger,Strikes, Hunger
D005260 Female Females
D006843 Hydrocarbons, Chlorinated Hydrocarbon compounds with one or more of the hydrogens replaced by CHLORINE. Chlorinated Hydrocarbon,Chlorinated Hydrocarbons,Organochlorine Compound,Chlorine Compounds, Organic,Organochlorine Compounds,Compound, Organochlorine,Compounds, Organic Chlorine,Compounds, Organochlorine,Hydrocarbon, Chlorinated,Organic Chlorine Compounds

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