4-week inhalation toxicity study with a mixture of dichloroethylene and perfluorobutylethylene in rats. 2002

Linda Angevine Malley, and John F Hansen, and Nancy Everds, and David B Warheit
DuPont Haskell Laboratory, 1090 Elkton Road, PO Box 50, Newark, DE 19714, USA. linda.a.malley@usa.dupont.com

Inhalation studies were conducted to determine the potential subchronic toxicity of a mixture of trans-1,2-dichloroethylene (70%), cis-1,2-dichloroethylene (5%), and perfluorobutylethylene (25%). Groups of rats were exposed to 0, 400, 2000, or 8000 ppm concentrations of the mixture vapor 6 h/day, 5 days/wk, for a total of 20 exposures. Subgroups of rats were further observed during a 1-mo recovery period. Functional observational battery (FOB) and motor activity (MA) behavioral tests were conducted prior to initiation of the exposures, during exposure wk 4, and after a 1-mo postexposure recovery period. Clinical pathology evaluations were conducted at the end of the exposure period and after a 1-mo recovery period. At the end of the 4-wk exposure period, tissues from rats were collected, histologically processed, and evaluated by light microscopy. Test substance-related, biologically significant decreased body weights and body weight gains occurred in male and female rats exposed to 8000 ppm. In addition, test substance-related, statistically significant decreases in food consumption and/or food efficiency were observed in male rats exposed to 8000 ppm. During exposures to 8000 ppm, some rats exhibited tremors and ataxia. Usually tremors and ataxia were observed within 1 h after initiation of the daily exposure period and were observed during each exposure day. Tremors were also observed during 1 exposure day in the 2000 ppm animals. In addition to the tremors and ataxia, rats exposed to 2000 ppm or 8000 ppm had a diminished and/or no alerting response to a sharp, sound stimulus during each of the daily exposure periods. These effects were transient since no clinical observations of compromised neurological function were detected when the rats were evaluated upon return to the animal room following exposure. Daily reoccurrence of this apparently acute effect in the 8000 ppm group did not produce enduring neurological changes since there were no test substance-related effects on FOB parameters or on MA conducted the day following the last exposure or during the recovery period. In addition, there were no toxicologically significant changes in hematology, clinical chemistry, or urinalysis parameters in either males or females for any exposure concentration; and there were no test substance-related gross or microscopic morphological changes in males or females administered any exposure concentration. Under the conditions of the study, the no-observed-effect level (NOEL) was 400 ppm in males and females based on clinical signs of toxicity during exposure to 2000 or 8000 ppm.

UI MeSH Term Description Entries
D008297 Male Males
D009422 Nervous System Diseases Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle. Neurologic Disorders,Nervous System Disorders,Neurological Disorders,Disease, Nervous System,Diseases, Nervous System,Disorder, Nervous System,Disorder, Neurologic,Disorder, Neurological,Disorders, Nervous System,Disorders, Neurologic,Disorders, Neurological,Nervous System Disease,Nervous System Disorder,Neurologic Disorder,Neurological Disorder
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
D004435 Eating The consumption of edible substances. Dietary Intake,Feed Intake,Food Intake,Macronutrient Intake,Micronutrient Intake,Nutrient Intake,Nutritional Intake,Ingestion,Dietary Intakes,Feed Intakes,Intake, Dietary,Intake, Feed,Intake, Food,Intake, Macronutrient,Intake, Micronutrient,Intake, Nutrient,Intake, Nutritional,Macronutrient Intakes,Micronutrient Intakes,Nutrient Intakes,Nutritional Intakes
D005260 Female Females
D005466 Fluorocarbons Liquid perfluorinated carbon compounds which may or may not contain a hetero atom such as nitrogen, oxygen or sulfur, but do not contain another halogen or hydrogen atom. This concept includes fluorocarbon emulsions, and fluorocarbon blood substitutes. Perfluorinated and related polyfluorinated chemicals are referred to as PFAS and are defined as chemicals with at least two adjacent carbon atoms, where one carbon is fully fluorinated and the other is at least partially fluorinated. Fluorocarbon,Fluorocarbon Emulsion,Fluorocarbon Emulsions,Fluorotelomer Phosphate Esters,N-Alkyl Perfluoroalkyl Sulfonamido Carboxylates,PFAS Per- and Polyfluoroalkyl Substances,PFC Perfluorinated Chemicals,PFECAs Perfluoropolyether Carboxylic Acids,Per- and Polyfluoroalkyl Substances,Perfluoroalkane Sulfonamides,Perfluoroalkyl Carboxylates,Perfluoroalkyl Ether Carboxylates,Perfluoroalkyl Polyether Carboxylates,Perfluorocarbon,Perfluorocarbons,Perfluoropolyether Carboxylic Acids,Polyfluorocarbons,Fluorinated Telomer Alcohols,Fluoro-Telomer Alcohols,Polyfluorinated Telomer Alcohols,Telomer Fluorocarbons,Acids, Perfluoropolyether Carboxylic,Alcohols, Fluorinated Telomer,Alcohols, Fluoro-Telomer,Alcohols, Polyfluorinated Telomer,Carboxylates, Perfluoroalkyl,Carboxylates, Perfluoroalkyl Ether,Carboxylates, Perfluoroalkyl Polyether,Carboxylic Acids, Perfluoropolyether,Chemicals, PFC Perfluorinated,Emulsion, Fluorocarbon,Emulsions, Fluorocarbon,Esters, Fluorotelomer Phosphate,Ether Carboxylates, Perfluoroalkyl,Fluoro Telomer Alcohols,Fluorocarbons, Telomer,N Alkyl Perfluoroalkyl Sulfonamido Carboxylates,PFAS Per and Polyfluoroalkyl Substances,Per and Polyfluoroalkyl Substances,Perfluorinated Chemicals, PFC,Phosphate Esters, Fluorotelomer,Polyether Carboxylates, Perfluoroalkyl,Sulfonamides, Perfluoroalkane,Telomer Alcohols, Fluorinated,Telomer Alcohols, Polyfluorinated
D006845 Hydrocarbons, Fluorinated Inert liquid or gaseous halocarbon compounds in which FLUORINE replaces some or all HYDROGEN atoms. Fluorinated Hydrocarbons
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001259 Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions. Coordination Impairment,Dyssynergia,Incoordination,Ataxia, Appendicular,Ataxia, Limb,Ataxia, Motor,Ataxia, Sensory,Ataxia, Truncal,Ataxy,Dyscoordination,Lack of Coordination,Tremor, Rubral,Appendicular Ataxia,Appendicular Ataxias,Ataxias,Ataxias, Appendicular,Ataxias, Limb,Ataxias, Motor,Ataxias, Sensory,Ataxias, Truncal,Coordination Impairments,Coordination Lack,Impairment, Coordination,Impairments, Coordination,Incoordinations,Limb Ataxia,Limb Ataxias,Motor Ataxia,Motor Ataxias,Rubral Tremor,Rubral Tremors,Sensory Ataxia,Sensory Ataxias,Tremors, Rubral,Truncal Ataxia,Truncal Ataxias

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