Reproductive toxicity evaluation of acetaminophen in Swiss CD-1 mice using a continuous breeding protocol

Acetaminophen (APAP) was evaluated for reproductive toxicity in Swiss CD-1 mice using a continuous breeding protocol. APAP was administered in the diet at 0, 0.25, 0.5, and 1.0% (w/w), which represented average daily intakes of 0, 357, 715, and 1430 mg APAP/kg/day, respectively. Exposure of parental (P) breeding pairs to 1% APAP in the diet for 14 weeks during cohabitation significantly decreased the number of litters per pair, and reduced, although not significantly, the number of live pups per litter. Importantly, 6 of 19 high-dose P pairs failed to produce a fifth litter, and this fully accounted for the diminished number of litters in this group. In addition, the fifth litter that was produced by the 13 high-dose P pairs averaged only about 9 live pups per litter, which correspondingly reduced the overall group average for this parameter. In comparison, the control and two lower-dose P pairs produced 11 or 12 live pups per litter on average. Although the birth weights for F1 pups in the final litter were unaffected by prenatal APAP exposure, postnatal growth was adversely affected as evidenced by retarded weight gain as measured at 28 and 74 +/- 10 days of age for all three dietary levels. At 1% APAP this weight gain effect was more pronounced at Day 28 than at Day 74 +/- 10, suggesting that nursing pups may have been exposed to higher concentrations or may be more sensitive to APAP and/or an active metabolite than were the young adults.(ABSTRACT TRUNCATED AT 250 WORDS)