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