[Application of benchmark dose method in reproduction/developmental toxicity screening test].

OBJECTIVE:To estimate the benchmark dose( BMD) of the reproduction /developmental toxicity screening test in rats and compare with the non-observed adverse effect level( NOAEL). METHODS:A total of 120 SD rats were divided into 4 groups and feed with nitrile compound at 0, 12. 5, 50, 200 mg/kg BW for females and 0, 10, 40, 150 mg/kg BW for males, respectively. Rats were orally dosed with the substance for a period of 54 days. The toxic signs, body weight, food consumption, organ weight, organ weight coefficient and pathological lesion of genital organs of parent rats, and the number of live and dead births, litter weight and abnormalities were observed. The results was analyzed and estimated by benchmark dose method by software of BMDS 2. 6. The lower confidence limit on the benchmark dose( BMDL) can be obtained to calculate the reference dose. RESULTS:After 1, 2, 5 and 6 week administration, the daily food consumption of female rats in high-dose group(( 16. 39 ± 0. 75), ( 16. 57 ± 0. 24), ( 43. 65 ± 1. 94) and( 31. 18 ± 6. 93) g), decreased significantly, compared with control group(( 20. 79 ± 0. 11), ( 18. 30 ± 0. 87), ( 46. 20 ± 1. 90) and( 43. 57 ± 10. 67) g)( P < 0. 01). The body weight of 20 days pregnant rats in high-dose group(( 353. 67 ±29. 73) g), significantly decreased, compared with control group(( 389. 83 ± 29. 46) g)( P < 0. 01). The litter weight of live pups at day 0(( 64. 97 ± 37. 75) g) and day 4( 108. 66 ± 62. 67) g) in high-dose group decreased obviously, compared with control group(( 94. 39 ± 23. 00) g, ( 156. 37 ± 29. 06) g)( P < 0. 05). The implantation loss rates increased in medium and high-dose groups( 19. 6% and 47. 0%) with significant difference, compared with control group( 5. 7%)( P < 0. 01). The key toxic effect was implantation loss and NOAEL of the chemical was 12. 5 mg/kg BW. The BMDL was 17. 8mg/kg BW, from the nested data of implantation loss. CONCLUSION:In the reproduction /developmental toxicity screening test, the reference dose obtained from BMD method is17. 8 mg/kg BW.