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ToxSci Advance Access published online on September 21, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi335
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received July 29, 2005
Accepted September 15, 2005

Systems Toxicology

Toxicological Effects of Gestational and Lactational Exposure to a Mixture of Persistent Organochlorines in Rats: Systemic Effects

Ih Chu 1*, Wayne J. Bowers 1, Don Caldwell 2, Jamie Nakai 1, Olga Pulido 2, Al Yagminas 1, Michael G. Wade 1, David Moir 1, Santokh Gill 2, and Rudi Mueller 2

1 Environmental and Occupational Toxicology Division, Healthy Environments and Consumer Safety Branch, Ottawa, Ontario K1A 0L2, Canada
2 Toxicology Research Division, Health Products and Foods Branch, Health Canada, Ottawa, Ontario K1A 0L2, Canada

* To whom correspondence should be addressed.
Ih Chu, E-mail: Ih_chu{at}hc-sc.gc.ca


  Abstract

A large multi-disciplinary study was conducted to investigate the systemic, neurodevelopmental, neurochemical, endocrine and molecular pathological effects of a mixture of reconstituted persistent organochlorine pollutants (POP) based on the blood profiles of Canadians residing in the Great Lakes/St. Lawrence region. This report outlines the overall study design, and describes specifically the systemic effects in rat offspring perinatally exposed to the POP mixture. Maternal rats were administered orally 0, 0.013, 0.13, 1.3 or 13 mg/kg bw/day of the mixture from gestational day (GD) 1 to postnatal day (PND) 23. Positive and negative controls were given Aroclor 1254 (15 mg/kg bw/day) and corn oil (vehicle), respectively. The rat pups were reared, culled to 8 per litter, and killed on postnatal days 35, 70 and 350 when tissues were collected for analysis. Exposure to high doses of the mixture elicited clinical, biochemical and pathological changes and high mortality rates in rat offspring. Aroclor 1254 produced similar effects but a lower mortality than was seen in POP mixture groups. Biochemical changes consisted of increased liver microsomal activities and elevated serum cholesterol. Hepatomegaly was observed in the highest dose group of the mixture and in the positive control. Liver, thymus and spleen were the target organs of action. Microscopic changes in the liver consisted of vacuolation and hypertrophy, while those in the thymus were characterized by reduced cortical and medullary volume. The spleen showed a treatment related reduction in lymphocyte density and lymphoid areas. This study demonstrates that exposure to the POP mixture up to 13 mg/kg/day perinatally produced growth suppression, elevated serum cholesterol, increased liver microsomal enzyme activities, and immunopathological changes in the thymus and spleen, and lethality. Most of the effects were seen at the dose levels much higher than expected human exposure.

Keywords: Systemic toxicity; organochlorine mixtures; Aroclor 1254; PCBs; Great Lakes/St. Lawrence region.
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