Table 4 : Adverse effects observed in the multi-generation study with Sprague Dawley rats which received genistein in the food [10].


NOAEL
(mg/(kg bwxd))
LOAEL
(mg/(kg bwxd))
Sex/generation Endpointa Effect (I: increased,
D: decreased A: accelerated,
C: changed,
0: no effect)
Estrogen-mediated activity Androgen-mediated activity Thyroid-
related
activity
Steroido-
genesis-related
activity
Endpoint potentially
sensitive to EATS
modality
agonistic ant-agonistic agonistic ant-agonistic

10 51 F/F1-F4 Body weight: Preweaning D -- -- -- -- -- -- x
    F/F2, F4 Postweaning D -- -- -- -- -- -- --
0.5 10 F/F1 Body weight: Postweaning D -- -- -- -- -- -- x
7 35 M/F2-F4 Body weight: Preweaning D -- -- -- -- -- -- x
0.3 7 M/F1 Body weight: Preweaning D -- -- -- -- -- -- x
7 35 M/F1 Body weight: Postweaning D -- -- -- -- -- -- x
10 51 F/F0-F2, F4 Food consumption D -- -- -- -- -- -- --
7 /10 35 / 51 F + M/F2 Fertility, litter size D -- -- -- -- -- -- x
10 51 F/F1, F2 Developmental: AGD PND 2 D x x x x -- x --
0.5 10 F/F3 Developmental: AGD PND 2 D x x x x -- x --
7 35 M/F1 Developmental: AGD PND 2 D x x   x -- x --
10 51 F/F1-F3 Development: Vaginal opening A x x x x -- x --
10 51 F/F1-F2 Reproductive: estrous cycle C x x x x -- x --
35 n.d. M/all Reproductive Organs 0 -- -- -- -- -- -- --
51 n.d. F/all Organ histology 0 -- -- -- -- -- -- --
0.3 7 M/F1, F2d Organ histology: mammary Alveolar/ductal xb -- -- -- -- -- --
7 35 M/F0 gland at 20 wk hyperplasia -- -- -- -- -- -- --
0.3 7 M Organ histology: kidney, I (x)c -- -- -- -- -- --
      tubulus calcification -- -- -- -- -- -- -- --

*: Data from summary table; a: significant changes relative to control; b: Not mentioned in OECD GD 150 [2] for EATS endpoints in TG 416, but for TG 408, TG 451-3, TG 443 and 407. Also, evaluation of NTP-studies concluded that mammary gland
hyperplasia in the male rat is one of the most sensitive markers of estrogenic endocrine disruption [11]; c: possibly related to estrogenic activity [10]; d: a significant positive trend was observed in F1, F2, and F3.

Schuhmacher-Wolz et al.Journal of Toxicology and Health  2017 4:2DOI : 10.7243/2056-3779-4-2