Two-generation reproductive toxicity of lufenuron in SD rats / 中国职业医学

ABSTRACT

OBJECTIVE: To obtain information on the toxicity of lufenuron on the reproduction ability and the growth and development of offspring in female and male rats through two-generation reproduction toxicity study. METHODS: The specific pathogen free healthy SD rats were randomly divided into control group and low-, medium-and high-dose lufenuron groups, with 60 rats in each group, half females and half males. Rats in the low-, medium-and high-dose lufenuron groups were respectively fed with lufenuron at the dose of 5.0, 20.0 and 80.0 mg/(kg body weight·day) for 8 weeks before mating. The control group was fed with standard foot. The reproductive index, brain and reproductive organ coefficients and pathological changes were observed in P and F1 parents. The birth and growth indexes of the offspring were measured. RESULTS: i) P generation: from the 14 th day, the female rats in the medium-dose group had lower body weight than that of the female control group(P<0.05); from the 35 th day, the body weight was lower than that of the female low-dose group(P<0.05). From the 14 th day, the female rats in the high-dose group had lower body weight than that of the other three female groups(P<0.05). From the 14 th day, the male rats in the medium-and high-dose groups had lower body weight than that of the male control group and low-dose group(P<0.05). The body weight of pregnant rats in the parental high-dose group was lower than that of the control group, low-dose group, and medium-dose group at day 0, 7, 14, 19 of the pregnancy duration(P<0.05). The body weight of pregnant rats in the parental medium-dose group was lower than that of the low-dose group on day 0 of the pregnancy duration, and lower than that of the control and low-dose groups on day 7 and 14(P<0.05). The conception rate, the new-borne survival rates and the feeding survival rate of female rats in the high-dose group was lower than that of the other three female groups(P<0.008). The new-borne feeding survival rate of female rats in the medium-dose group was lower than that of the control group and low-dose group(P<0.008). The organ coefficients of brain in female rats in the medium-and high-dose groups were higher than that of the female control group and low-dose group(P<0.05). The organ coefficients of brain and testis in male rats in the medium-and high-dose groups were higher than that of the control group and low-dose group(P<0.05). The organ coefficient of epididymis in male rats in the high dose group was lower than that of the other three male groups(P<0.05). ii) F1 generation: the body weight of female rats in the low-and medium-dose group was higher than that of the female control group on the 42 th day(P<0.05). The body weight of male rats in the low-dose group was higher than that of the male control group on the 42 th, 49 th, and 56 th days(P<0.05). The body weight of male rats in the medium-dose group was higher than that of the male control group on the 14 th, 21 th, 42 th, 49 th, and 56 th days(P<0.05). The new-borne survival rate in the low-dose group was lower than that of the control group(P<0.017). The body weight of new-borne rats in the high-dose group on day 4 of birth was lower than that in the other three female groups(P<0.05). iii) F2 generation: the body weight of male rats in the male medium-dose group was lower than that in the control group on day 21 of birth(P<0.05). CONCLUSION: The reproductive and developmental toxicity of lufenuron is found in rats in the medium-and high-dose groups. Toxicities including low body weight, conception rate, new-borne survival rate and feeding survival rate are found in P generation; low body weight and feeding survival rate are found in F1 generation; low body weight is found in male F2 generation. The no-observed-adverse-effects levels of lufenuron in two-generation reproductive study are 5.87 mg/(kg·d) for females and 5.09 mg/(kg·d) for males in SD rats.