Consequences of Aroclor 1254 ingestion on the menstrual cycle of rhesus (Macaca mulatta) monkeys.
A group of 80 female rhesus (Macaca mulatta) monkeys were randomly distributed to four similar test rooms (20 monkeys/room) and then randomly allocated to one of five test groups (four females/test group/room). The objective of the study was to ascertain the toxicological and reproductive effects of Aroclor 1254 ingestion at dose levels of 0, 5, 20, 40 or 80 microg Aroclor 1254/kg body weight per day (Arnold et al., 1993a,b, 1995, 1996, 1997). It was deemed necessary to establish the menstrual patterns for all the monkeys both before and after the start of dosing so as to provide an appropriate baseline from which potential treatment effects could be ascertained. The data presented herein were obtained during the first 3 years after the start of dosing, or the study's pre-mating phase. At the end of the first 2 years of dosing, the monkeys attained a qualitative pharmacokinetic steady state regarding the levels of polychlorinated biphenyls in their adipose tissue. Upon termination of the study, a number of monkeys were found to have endometriosis, adenomyosis or uterine leiomyomas (Arnold et al., 1996, 1997). These monkeys were designated as having gynecological abnormalities which were considered to be a factor in the analysis of the menstrual data. The menstrual data (i.e. menses frequency, cycle length and menses duration) were subjected to a statistical assessment to see whether year, quarter, gynecological abnormalities or dose of Aroclor 1254 had any effect on menses frequency, menstrual cycle length (i.e. the first day of menses until the day prior to the start of the next menses) and/or menses duration (i.e. the number of days of haemorrhagic discharge). The only consistent statistically significant effect found was that gynecological abnormalities increased menses duration (P<0.05) in all 12 quarters of the premating observation period. This effect was significant during both the pre- (P=0.0004) and post- (P< or =0.0001) pharmacokinetic steady-state intervals. While there was some indication of seasonality regarding menstrual cycle length and menses duration when these data were compared on a quarterly basis during the first 2 years of the study (P=0.043; P< or =0.0001, respectively), this effect was not evident during the third year (P=0.21; P=0.31, respectively). In particular, the effect of quarter on menses cycle length was most evident during the first year, with the shortest cycles occurring during the first or spring quarter and the longest in the third or fall quarter. However, menses duration was shortest in the first quarter during the first 2 years and tended to peak in the second quarter of all 3 years, while generally diminishing in the third and fourth quarters. There was also an increase in menses duration with increasing time on test for all groups. In addition, Aroclor 1254 treatment appeared to have some effect on menses duration when menses duration was plotted against dose group, but the effect was not statistically significant (P>0. 05). It was concluded that the ingestion of Aroclor 1254 at dose levels up to 80 microg/kg body weight/day by rhesus monkeys did not have any appreciable biological effect on menstrual frequency, menstrual cycle length or menses duration. However, gynecological abnormalities significantly increased menses duration during the three-year observation period.
Bryce
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Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Postal locator 2202D1, Health Canada, Ottawa, Ontario, K1A 0L2, Canada.
Hayward
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Stapley
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Arnold
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D000818:Animals; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D005260:Female; D008253:Macaca mulatta / Q000502:physiology*; D008597:Menstrual Cycle / Q000187:drug effects*
D020111:Chlorodiphenyl (54% Chlorine)