Table 6 Description and supporting evidence of the KEs included in postulated MoA for BPAF in male adult exposure
Brief description of key event | Supporting evidence | |
|---|---|---|
MIE 1 | Androgen receptor inhibition (two parallel MIEs are suggested, current knowledge in endocrinology does not provide sufficient knowledge to conclude whether they are indeed parallel or whether one of them precedes the other) | In vitro mechanistic: ●Androgen receptor antagonist binding IDs: 75–76 ●Androgen receptor antagonist activity IDs: 19, 21–22, 43, 64, 78, 81, 87 In vivo mechanistic: ●Prostate weight decrease (adult exposure) ID: 60 ●Epididymis weight decrease (adult exposure) ID: 88 ●Seminal vesicles weight decrease (adult exposure) ID: 60 |
MIE 2 | Altered steroidogenesis | In vitro mechanistic: ●Steroidogenesis alteration IDs: 4–5, 87 In vivo mechanistic: ●Steroidogenesis gene/protein expression alteration (adult exposure) IDs: 55, 58, 83 ●Testosterone level decrease in male (adult exposure) ID: 55 ●FSH level increase in male (adult exposure) ID: 55 ●LH level increase in male (adult exposure) ID: 55 |
KE1 | Dysfunction of male reproductive organs | EATS mediated: â—ŹTestis histopathology alteration (adult exposure) IDs: 60, 88 â—ŹProstate weight decrease (adult exposure) ID: 60 â—ŹEpididymis weight decrease (adult exposure) ID: 88 â—ŹSeminal vesicles weight decrease (adult exposure) ID: 60 â—ŹSeminal vesicles histopathology alteration (adult exposure) ID: 88 |
AO | Impaired male fertility | Sensitive but not diagnostic of EATS: â—ŹFertility decrease (adult exposure) ID: 88 |