Acute toxicologic and neurotoxic effects of inhaled 1,2-dichloroethane in adult Fischer 344 rats.
Acute toxicologic and neurotoxic effects were evaluated in Fischer 344 rats exposed to 0, 50, 200, 600, or 2000 ppm 1,2-dichloroethane (ethylene dichloride; EDC) for 4 h or 0, 50, 100 or 150 ppm for 8 h. Neurobehavioral and neuropathologic effects were assessed using a functional observational battery (FOB; baseline, days 1, 8, and 15), and by light microscopy, respectively. Acute toxicologic effects were assessed by bronchoalveolar lavage (BAL) and histopathology of the respiratory tract and selected target organs. Neurobehavioral effects consistent with central nervous system (CNS) depression were present at concentrations >200 ppm and were restricted to day 1. There were no neuropathologic changes in the CNS, however, olfactory epithelial regeneration 15 days after exposure to > or = 200 ppm was observed. The no-observed-effect concentration (NOEC) for behavioral neurotoxicity was 200 ppm EDC for 4 h. There were no effects on BAL parameters in any exposure group. Exposure to 2000 ppm EDC altered adrenal gland, kidney, and liver weights, and resulted in morphologic alterations in the kidney and liver. Degeneration/necrosis of the olfactory epithelium was observed at > or = 200 ppm for 4 h and > or = 100 ppm for 8 h. Based on olfactory epithelial degeneration/necrosis, the most sensitive indicator of toxicity in this study, the overall NOEC was 50 ppm EDC for up to 8 h in rats.
Hotchkiss
J A
JA
Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI 48674, USA. jahotchkiss@dow.com
Andrus
A K
AK
Johnson
K A
KA
Krieger
S M
SM
Woolhiser
M R
MR
Maurissen
J P
JP
D000280:Administration, Inhalation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D018893:Bronchoalveolar Lavage; D003863:Depression / Q000139:chemically induced* / Q000503:physiopathology; D005025:Ethylene Dichlorides / Q000633:toxicity*; D005260:Female; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D009498:Neurotoxins / Q000633:toxicity*; D009831:Olfactory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012137:Respiratory System / Q000187:drug effects / Q000473:pathology; D023382:Toxicity Tests, Acute
D005025:Ethylene Dichlorides; D009498:Neurotoxins; C024565:ethylene dichloride