4-week inhalation toxicity study with a mixture of dichloroethylene and perfluorobutylethylene in rats.
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.
DuPont Haskell Laboratory, 1090 Elkton Road, PO Box 50, Newark, DE 19714, USA. linda.a.malley@usa.dupont.com
Linda Angevine
LA
Malley
John F
JF
Hansen
Nancy
N
Everds
David B
DB
Warheit
D000818:Animals; D001259:Ataxia / Q000139:chemically induced*; D004000:Dichloroethylenes / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D005466:Fluorocarbons; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage / Q000633:toxicity*; D019570:Inhalation Exposure; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D012737:Sex Factors; D015430:Weight Gain; D015431:Weight Loss
D004000:Dichloroethylenes; D005466:Fluorocarbons; D006845:Hydrocarbons, Fluorinated; C068177:3,3,4,4,5,5,6,6,6-nonafluoro-1-hexene