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Toxicological consequences of aroclor 1254 ingestion by female rhesus (Macaca mulatta) monkeys and their nursing infants. Part 3: Post-reproduction and pathological findings
Authors:D.L. Arnold   E.A. Nera  R. Stapley  F. Bryce  S. Fernie  G. Tolnai  D. Miller  S. Hayward  J.S. Campbell  I. Greer
Affiliation:

Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Protection Branch, Health Canada, Ottawa, Canada K1A 0L2

Bureau of Biostatistics and Computer Applications, Food Directorate, Health Protection Branch, Health Canada, Ottawa, Canada K1A 0L2

Abstract:A group of 80 menstruating rhesus (Macaca mulatta) monkeys were randomly allocated to four similar rooms (20 monkeys/room) and then to one of five dose groups (four females/dose group room). Each day the monkeys self-ingested capsules containing doses of 0, 5, 20, 40 or 80 μg Aroclor 1254/kg body weight. After 25 months of continuous dosing, approximately 90% of the treated females had attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl (PCB) in their nuchal fat pad. Concurrently, sebaceous glands were being examined for changes analagous to chloracne. Subsequently, the females were paired with untreated males. The infants' blood PCB levels at birth were not correlated with its dam's dose or blood PCB level. However, there was an association between an infants preweaning blood PCB levels and its dam's dose and PCB milk levels. After weaning, the infants were not dosed with PCB. The half-life for the PCB in the infants' blood was determined and found to be slightly more than 15 wk. After 6 yr on test, three monkeys from the 0, 5, 20 and 40 μg dose groups were randomly allocated to a depletion study to ascertain the half-lives of specific PCB congeners (Mes et al., Chemosphere 1995, 30, 789–800). Concurrently, necropsies began of the remaining females, and of seven infants from the treated dams and four infants from the control dams, which had attained an age of 2 yr. Approximately 3 yr later, the depletion monkeys were necropsied. The only statistically significant treatment-related pathological changes found during the study were in the adult females, in which an involution of the sebaceous glands and a dose related increase in liver weight due to hyperplasia were evident.
Keywords:Abbreviations: ALT, alanine aminotransferase   ANCOVA, analysis of covariance   ANOVA, analysis of variance   AP, alkaline phosphatase   AST, aspartate aminotransferase   BUN, blood urea nitrogen   CPK, creatinine phosphokinase   GT, γ-glutamyltransferase   FTI, free thyroxine index   Hb, haemoglobin concentration   Hct, haematocrit   H, haematoxylin   E, eosin   Ket HCl, ketamine hydrochloride   LDH, lactate dehydrogenase   MCH, mean corpuscular haemoglobin   MCHC, mean corpuscular haemoglobin concentration   MPV, mean platelet volume   PAS, periodic acid Schiff   PCB, polychlorinated biphenyls   RBC, erythrocyte count   PDW, platelet distribution width   RDW, red cell distribution width   T3, triiodothyronine   T4, thyroxine   TCB, tetrachlaorobiphenyl   WBC, total leucocyte count
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