Reproductive toxicity assessment of alkyl dimethyl benzyl ammonium chloride and didecyl dimethyl ammonium chloride in CD® rats.

AIM

To determine the potential of alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) to induce reproductive toxicity in CD® rats in two independent 2-generation reproduction studies conducted according to Good Laboratory Practices and standardized testing guidelines.

MATERIALS AND METHODS

Male and female rats (parents and offspring) were allowed continual free access to diets containing concentrations of ADBAC (0, 300, 1,000, or 2,000 ppm) or DDAC (0, 300, 750, or 1,500 ppm), beginning with F generation adults at 10 weeks prior to breeding.

RESULTS

No clinical signs of toxicity were observed in parental rats or their offspring in either study. Dietary exposure of parental rats to ADBAC or DDAC at the highest concentrations produced transient decreases in body weight and/or body weight changes with no or minimal corresponding reduction in food consumption. Offspring (F and F ) in the highest concentration group in each study also exhibited reduced body weights, often with a corresponding reduction in weight change, beginning on postnatal day (PND) 14 through weaning on PND 28. This reduction in pup body weight corresponded to initiation of self-feeding.

CONCLUSIONS

Based on reduced body weights, the no observed adverse effect level (NOAEL) for adult and offspring systemic toxicity was 1,000 ppm for ADBAC and 750 ppm for DDAC (equivalent to approximate daily oral doses of 59 and 45 mg/kg/day, respectively). The reproductive and developmental NOAEL for F , F , and F generation male and female rats was 2,000 ppm for ADBAC and 1,500 ppm for DDAC (equivalent to approximate daily oral doses of 118 and 91 mg/kg/day, respectively).