7 Journal of Toxicology Generation Dose (mg/kg/day) (n) Table 4: Organ weight changes in male and female breeding Sprague-Dawley rats in the F0 and F1 generations of the two-generation rat study. F0 F1 0 (n = 26) 200 (n = 26) 1000 (n = 26) 2000 (n = 26) 0 (n = 22) 200 (n = 22) 1000 (n = 20) 2000 (n = 26) Male Female Thyroids, absolute organ weight (mg)A 30.01 ± 5.45C 31.65 ± 5.94 0 (n = 26) oTrhgyarnoiwdes,igrhelta(tmiveg)B 5.23 ± 0.68 5.33 ± 0.86 5.33 ± 0.73 5.34 ± 0.78 4.55 ± 0.61 4.76 ± 0.73 5.48 ± 0.90∗∗ 4.94 ± 0.58 Adrenals, absolute 61.81 ± 7.05 63.95 ± 10.16 59.48 ± 7.40 68.90 ± 9.01∗∗ 62.18 ± 7.30 63.96 ± 5.83 57.61 ± 7.52 62.28 ± 9.25 organ weight (mg) Adrenals, relative 10.88 ± 1.31 10.82 ± 1.68 10.57 ± 1.28 12.10 ± 1.58∗∗ 9.41 ± 1.14 9.56 ± 1.07 8.95 ± 1.08 9.62 ± 1.57 organ weight (mg) Seminal Vesicles, absolute organ 3.11 ± 0.33 2.90 ± 0.37 3.12 ± 0.37 3.05 ± 0.34 3.40 ± 0.29 3.26 ± 0.44 3.23 ± 0.39 3.13 ± 0.37 weight (g) Seminal vesicles, relative organ weight 0.55 ± 0.07 0.49 ± 0.09∗ 0.55 ± 0.08 0.54 ± 0.06 0.52 ± 0.08 0.49 ± 0.01 0.51 ± 0.08 0.48 ± 0.06 (g) Generation F0 F1 Dose (mg/kg/day) 200 (n = 26) 1000 (n = 26) 2000 (n = 26) 0 (n = 18) 200 (n = 17) 1000 (n = 18) 2000 (n = 19) (n) 29.94 ± 3.88 30.32 ± 3.95 30.19 ± 4.48 31.89 ± 4.91 35.15 ± 5.27∗∗ 32.09 ± 4.18 Lwieviegrh,tab(gs)olute organ 13.70 ± 1.30 13.99 ± 1.08 Lwieviegrh,tre(lga)tive organ 3.86 ± 0.32 4.05 ± 0.31 14.39 ± 1.62 14.48 ± 1.11 15.01 ± 1.28 15.45 ± 1.86 16.02 ± 1.46 15.71 ± 1.35 4.17 ± 0.35∗∗ 4.23 ± 0.29∗∗ 4.12 ± 0.34 4.17 ± 0.41 4.36 ± 0.33 4.42 ± 0.33∗ Signiﬁcantly diﬀerent from control: ∗P < .05, ∗∗P < .01; Aabsolute organ weight is the weight of the organ; Brelative organ weight is the weight of the organ relative to the body weight at necropsy (body weight ratio); Cmean± standard deviation; n: number of male and female rats per dose group. Table 5: Eﬀect of SE5-OH administration on the reproductive performance of the F0 generation rat dams. (Dmogse/kg/day) Mean estrus cycle iIrnrceigduelnacreeostfrus cycle Number of Mesatrtuinsg pDearyioodf conceiving Copulation index (%)A Fertility index (%)B 0 4.26 ± 0.43# 0.0 ± 0.0 2.5 ± 1.8 100.0 96.2 (n = 25) 1/26 (n = 26) (n = 26) (26/26) (25/26) 200 4.18 ± 0.32 0.0 ± 0.0 2.8 ± 1.6 92.3 100.0 (n = 24) 2/26 (n = 26) (n = 24) (24/26) (24/24) 1000 4.21 ± 0.40 0.0 ± 0.0 2.9 ± 2.7 92.3 91.7 (n = 26) 0/26 (n = 26) (n = 24) (24/26) (22/24) 2000 4.15 ± 0.38 0.0 ± 0.0 3.3 ± 2.5 96.2 88.0 (n = 24) 2/26 (n = 26) (n = 25) (25/26) (22/25) #Mean ± standard deviation; Anumber of copulated females/number of pairs; Bnumber of pregnant females/number of copulated females; n: number of mating pairs. There has been a concern that ingestion of soy isoﬂavones may lead to adverse eﬀects on testes and ovaries [33–36]. Unlike diethylstilbestrol (DES), equol at 1000 μg/animal/day injected subcutaneously for ﬁve days failed to demonstrate estrogenic, or antiestrogenic activity in the uterine wall of neonatal Sprague-Dawley (SD) rats [37]. Other research found that equol administration directly to the uterine horn in ovariectomized rats did not increase uterine weight, and although equol did weakly bind to the estrogen receptor with a high dissociation rate, it did not demonstrate antiestrogenic activity [38]. In concert with ﬁndings reported by Thompson et al. [38], Wood et al. [39] found that high doses of genistein and daidzein or equol had minimal uterotrophic or mammotrophic eﬀects in an ovariectomized monkey (Macaca fascicularis) model. In the normal postmenopausal mammary gland of cynomolgus macaques, equol at an equivalent human dose of 105 mg/day for greater than six months lacked estrogenic eﬀects, and did not promote lesions in the mammary tissue [40]. Rachon et al. [41– 43] found that equol in the diet at 400 mg per kg of food