10 Journal of Toxicology Table 10: Litter size and viability index of the F1 generation rat pups exposed to SE5-OH during gestation and through lactation of the F0 dams. 0 n 200 Dose (mg/kg/day) n 1000 n 2000 n Number of total oﬀspring at birth Males #7.6 ± 2.7 24 7.3 ± 2.5 23 7.4 ± 2.0 22 6.7 ± 1.9 22 Females 7.0 ± 2.0 24 7.3 ± 2.6 23 6.5 ± 1.7 22 7.1 ± 2.3 22 Total 14.6 ± 2.8 24 14.7 ± 1.9 23 14.2 ± 1.8 22 13.8 ± 2.3 22 (M/F) (183/168) (169/169) (162/144) (147/157) Number of live oﬀspring at birth Males 7.5 ± 2.8 24 7.3 ± 2.6 23 7.2 ± 2.3 22 6.6 ± 2.0 22 Females 6.9 ± 2.0 24 7.2 ± 2.4 23 6.4 ± 2.2 22 7.1 ± 2.3 22 Total 14.4 ± 3.0 24 14.4 ± 1.6 23 13.6 ± 3.3 22 13.8 ± 2.3 22 (M/F) (179/166) (167/165) (159/140) (146/157) Number of live oﬀspring on PND 4 before culling Males 7.4 ± 2.8 24 7.2 ± 2.6 23 7.1 ± 2.4 22 6.5 ± 1.8 22 Females 6.7 ± 2.0 24 7.1 ± 2.3 23 6.2 ± 2.1 22 7.0 ± 2.3 22 Total 14.1 ± 2.9 24 14.3 ± 1.6 23 13.3 ± 3.5 22 13.5 ± 2.2 22 (M/F) (178/160) (166/164) (156/137) (144/154) Number of live oﬀspring on PND 4 after culling Males 3.9 ± 0.9 24 4.0 ± 0.2 23 4.0 ± 0.2 21 4.0 ± 0.2 22 Females 3.9 ± 0.4 24 4.0 ± 0.2 23 4.0 ± 0.2 21 4.0 ± 0.3 22 Total 7.8 ± 1.2 24 8.0 ± 0.0 23 8.0 ± 0.0 21 8.0 ± 0.2 22 Number of live oﬀspring on PND 21 Males 3.9 ± 0.9 24 4.0 ± 0.2 23 4.0 ± 0.4 21 3.9 ± 0.3 22 Females 3.9 ± 0.4 24 4.0 ± 0.2 23 4.0 ± 0.2 21 3.9 ± 0.4 22 Total 7.8 ± 1.2 24 8.0 ± 0.0 23 7.9 ± 0.3 21 7.8 ± 0.5 22 Viability indexA (%) PND 0 96.86 ± 10.27 24 98.50 ± 4.99 23 95.78 ± 19.81 22 99.62 ± 1.77 22 PND 4 98.23 ± 3.70 24 99.42 ± 1.92 23 93.75 ± 21.38 22 98.58 ± 4.28 22 PND 21 100.00 ± 0.00 24 100.00 ± 0.00 23 98.81 ± 3.76 21 98.30 ± 5.84 22 #Mean ± standard deviation; n: number of litters; PND: postnatal day; Aviability index: PND 0: (number of live oﬀspring born alive/number of oﬀspring born), PND 4: (number of oﬀspring alive on PND 4/number of oﬀspring born alive), PND 21: (number of live weanlings/number of live oﬀspring after culling). Although a signiﬁcant reduction in the number of implantations in this study is thought to have occurred due to lowered caloric intake in the high-dose pregnant dams, it still remains that there was an overall adverse eﬀect, albeit an indirect one (i.e., an eﬀect of reduced caloric intake on decreased body weights) and not a product of the intrinsic toxicity of SE5-OH on the reproductive ability of the rats in this study. Even though a transient decrease in body weight gain was noted in F0 and F1 dams of the 2000 mg/kg/day dose group, no changes were observed in fetal viability, intrauterine growth, and fetal morphology (external, skeletal, and visceral) that were attributed to SE5-OH treatment. Isolated embryo-fetal alterations were noted, but were not consistent with SE5-OH treatment or signiﬁcantly diﬀerent from controls. It is known that food restriction aﬀects the adult female rat reproductive capacity and may decrease the number of corpus luteum graviditatis [55, 56]. Equol administration to ovariectomized rats at approximately 27.48 mg/kg/day for six weeks [44] resulted in decreased weight gain, intra-abdominal fat, plasma leptin, and total cholesterol levels. Soy isoﬂavone administration to male, female, and ovariectomized rats reduced food intake and weekly body weight gain, while increasing serum isoﬂavones, including equol [57]. A decrease in implantations was noted at the 2000 mg/kg/day dose group; however, since no adverse eﬀects were noted on organ weights or histopathological examination of the reproductive organs, mating ability, fertility, pregnancy, parturition, or nursing behavior in F0 or F1 animals, this slight decrease in implantation number was not a substantive or meaningful eﬀect. Further, the absence of an eﬀect on the fecun- dity of the high-dose animals in the reproduction study indicates this decrease in implantation was an anomalous ﬁnding, and is supported by the lack of reproductive toxicity by daidzein in rats reported by Lamartiniere et al. [34]. In a previous work [26], no adverse observations were found in adult rats at up to 2000 mg/kg/day SE5- OH in a subchronic 90-day study. In the present study, no adverse toxicological observations were made at either the reproductive or developmental stages in the either sex