Toxicological consequences of toxaphene ingestion by cynomolgus ( Macaca fascicularis) monkeys. Part 1: pre-mating phase

Abstract

A total of 40 menstruating cynomolgus monkeys ( Macaca fascicularis) with an average age of 7.25±1.06 years (standard deviation), five male cynomolgus monkeys with an average age of 12.6±0.66 years, and five male cynomolgus males with an average age of 6.2±0.23 years were obtained from the Health Canada breeding laboratory. The females were initially randomized to the four test groups in accordance with their previous reproductive success and body weight. They were then randomly allocated between two similar environmentally-controlled rooms (20 females/room). The males were randomly assigned to one of the test rooms (six or four males/room). The female test groups self-ingested capsules containing doses of 0, 0.1, 0.4 or 0.8 mg (Groups A, B, C, D) of technical grade toxaphene/kg body weight/day (i.e. five females/dose group/room). The older males (Group E) were proven breeders and were used exclusively for mating and their capsules contained no toxaphene. The younger males (Group F) ingested capsules containing 0.8 mg of technical grade toxaphene/kg body weight/day. After 20 weeks of daily dosing, it was assumed, based on the results of a pilot study [Andrews P., Headrick K., Pilon J.-C., Bryce F., Iverson F. (1996) Capillary GC–ECD and ECNI GCMS charcterization of toxaphene residues in primate tissues during a feed study. Chemosphere 32, 1043–1053], that the treated monkeys had attained a qualitative pharmacokinetic steady state regarding the concentration of toxaphene in their adipose tissue and blood. On a daily basis, each monkey's feed and water consumption as well as its health were monitored. In addition, the females were swabbed daily to determine menstrual status. On a weekly basis, each monkey's body weight was determined and its dose of toxaphene adjusted. Detailed clinical examinations were conducted at intervals of 4 weeks or less. Periodically, starting prior to the initiation of dosing, blood samples were taken for serum biochemistry, haematology and toxaphene analysis. In addition, specimens from the nuchal fat pad were also obtained for toxaphene analysis. Statistical analysis did not reveal any effect of treatment on body weight gain, feed consumption, water consumption or haematological parameters during the 75-week pre-mating phase. The only serum biochemistry parameter which was consistently affected by treatment was cholesterol, the level of which decreased in a linear fashion as a consequence of dose, and this effect increased with time on test ( P=0.037). No other biological effects of toxaphene ingestion were found during the premating phase of this toxicological–reproduction study.