Toxicity of trans-nonachlor to Sprague-Dawley rats in a 90-day feeding study.
The chlordane constituent trans-nonachlor and its metabolite oxychlordane are among the most persistent chlordane-related contaminants and are found in tissues and milk from humans ingesting diets high in Arctic marine mammal fat. Although chlordane is no longer registered in North America, there is a need for toxicological data on chlordane-related contaminants found in food and the environment which are either structurally different or relatively more abundant than the constituents of the original chlordane mixture. Thus, a feeding study was undertaken to provide toxicological data on trans-nonachlor. Male and female Sprague-Dawley rats were exposed to 0, 5, 13 or 50 ppm trans-nonachlor in feed for 90 days and clinical, hematological and histopathological changes were assessed in each rat. Female rats were less able than males to metabolize and eliminate trans-nonachlor and, as a result, accumulated more trans-nonachlor in their adipose tissues. trans-Nonachlor, like technical chlordane and other organochlorines, induced liver microsomal enzymes in a pattern similar to phenobarbital. Endocrine effects included functional and morphological changes in the thyroid and adrenals. In male rats exposure to trans-nonachlor was associated with changes in endpoints indicative of increased oxidative stress, which may be related to both direct action on cellular targets or to secondary effects resulting from cytochrome P450 induction. The results indicate that subchronic trans-nonachlor exposure in rats induced hepatic changes with far-reaching metabolic and endocrine effects. Differences in target organ responses in male and female rats indicate that the sex-related metabolic differences affecting trans-nonachlor bioaccumulation and elimination merit further study.
Bondy
Genevieve
G
Toxicology Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada, K1A 0L2. Genevieve_Bondy@hc-sc.gc.ca
Curran
Ivan
I
Doucet
Josée
J
Armstrong
Cheryl
C
Coady
Laurie
L
Hierlihy
Lynn
L
Fernie
Susan
S
Robertson
Patrick
P
Barker
Michael
M
D000273:Adipose Tissue / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004703:Endocrine System / Q000187:drug effects*; D005260:Female; D006843:Hydrocarbons, Chlorinated / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D014018:Tissue Distribution
D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; C001870:nonachlor