R. W. Johnson Pharmaceutical Research Institute
Positive Signal: Dysmorphogenesis
A cross-species comparison between the rat and human was calculated using the nominal dose.
- LOAEL=lowest dose where dysmorphogenesis was observed in rats= 400 mg/kg/day
- NOAEL = highest non-teratogenic dose in the rat = 100 mg/kg/day
- MaxRHD = nominal maximum recommended dose in humans : 800 mg/day = 16 mg/kg/dayb
- RHD = nominal recommended dose in humans : 200 mg/day = 4 mg/kg/dayb
Therefore, the relative animal:human exposure ratios using the LOAEL in rats, and MHRD or RHD in humans are 25 and 100, respectively; and using the NOAEL in rats, and MHRD or RHD in humans are 6.25 and 25, respectively.
a = concern is increased for relative exposure ratios (animal:human) that are ? 10, and are decreased for exposure ratios ? 25. Ratios between 10-25 are not associated with any change in the perception of concern for this factor.
b = based on a 50 kg human