9-Aminoacridine hydrochloride (9AH), used as a topical antiseptic for humans, was tested for its effects on reproduction and fertility in CD-1 mice using the NTP Report # RACB protocol. Data from a two week dose-range-finding study (Task 1) were used to set exposure concentrations for the Task 2 continuous cohabitation study at 0.025, 0.05, and 0.1% in feed. Based on body weights and food consumption data, the estimated daily doses were nearly equal to 31, 66, and 145 mg/kg.
One male and 2 female control mice, and one female in the middle dose group, died during the 18 week Task 2 cohabitation phase. While the male mice in the high dose group gained less weight than controls, only high dose female mean body weights were significantly lower than control means during the study, by nearly equal to 10%. While 9AH consumption did not alter the number of litters/pair, the number of pups/litter or their viability, the pup weight adjusted for body weight was reduced by 9% in the high dose group. This pup weight reduction may be related to the reduced postpartum dam weights.
In the absence of changes in F0 fertility parameters, Task 3 was not conducted, and the last litter from the control, middle, and high dose groups was reared by their dams. Approximately 2/3rds of the pups in the high dose group died before pnd14, and pup weight at all times until weaning was reduced by nearly equal to 30%. Pup survival and weight gain in the middle dose group were not changed. The increased morbidity at the high dose left insufficient pups to evaluate for fertility effects. Thus, Task 4 was performed using controls and middle dose group mice.
During the Task 4 mating trial, 9AH had no effect on the number of pups/litter, or their viability or weight. Thus, there was no adverse reproductive effect noted in the second generation at 0.05% 9AH.
After the F2 pups were delivered and evaluated, the F1 adults were killed and necropsied. While female body weights at the middle dose were not changed, liver weight was increased by nearly equal to 30%, and adjusted kidney weights were reduced by nearly equal to 10%. For treated males, body weight was reduced by nearly equal to 10%, while adjusted liver weight was increased by nearly equal to 25%. Sperm indices at necropsy were unchanged, as was estrous cycle length.
Thus, 9AH induced some developmental toxicity, in the form of reduced F1 pup weight, at the same dose that also reduced dam weight, and at doses greater than those that increased F1 liver weight. No changes in other fertility indices were observed. These data suggest that , for 9AH, the hepatic effects are greater than any reproductive effects. Developmental toxicity could not be separated from the general toxicity.
NTIS#PB86163128/AS