Toxicological consequences of feeding PCB congeners to infant rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) monkeys.
In a study designed to minimize interspecies extrapolation of toxicological data, nine rhesus (Macaca mulatta) and 15 cynomolgus (M. fascicularis) day-old infant monkeys were separated from their dams following parturition and hand-reared using a liquid non-human primate formulation. The infants were randomly divided into a control and a treated group which received a mixture of polychlorinated biphenyl (PCB) congeners analogous to those found in breast milk from Canadian women. The concentration of congeners in the dosing media resulted in each infant receiving a total of 7.5 microg PCB congeners/kg body weight/day. The congeners were added either to the liquid formulation or to corn oil and administered to the back of the monkey's mouth for 20 weeks. Monthly blood and adipose specimens were obtained during the dosing period and then periodically until the monkey was necropsied or taken off test (minimum of 66 weeks on test) for congener analysis. Parameters such as body weight, formula consumption, tooth eruption, somatic measurements, haematology and serum biochemistry were monitored throughout the study. In addition, a qualitative evaluation of the absorption and depletion of the various congeners was undertaken as was an immunological evaluation. For the monitored parameters, very few differences were found to be statistically significant. For the immunological parameters, the only statistically differences found were a reduction over time for immunoglobulins M and G antibodies to sheep red blood cells (cyno, P = 0.025; rhesus, P = 0.002) and a treatment-related reduction in the levels of the HLA-DR cell surface marker (mean percent, P = 0.016; absolute levels, P = 0.027). There were some qualitative differences regarding absorption and depletion rates for the various congeners, but it could not be definitely ascertained whether these differences were due to species differences or dosing mode. However, statistically significant differences were found for treatment (P = 0.0293) as well as for species and vehicle regarding the concentration of PCB in blood (species;--P = 0.0399; treatment--P = 0.0001) and adipose tissue (species--P = 0.0489; treatment--P = 0.0001).
Arnold
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Toxicology Research Division, Bureau of Chemical Safety, Health Canada, Ottawa.
Bryce
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Mes
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Tryphonas
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H
Hayward
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Malcolm
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S
D000273:Adipose Tissue / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000833:Animals, Suckling / Q000254:growth & development* / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000187:drug effects; D007075:Immunoglobulin M / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D011897:Random Allocation; D014078:Tooth Eruption / Q000187:drug effects
D004785:Environmental Pollutants; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011078:Polychlorinated Biphenyls