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Table 4 Overview of the integrated lines of evidence for endocrine activity in mammals, classified by the weight of evidence evaluation as strong, moderate, weak, or no evidence for effect and the study IDs. For detailed information and data on general toxicity, see supplemental material - Appendix B

From: Assessment of the endocrine disrupting properties of bisphenol AF: a case study applying the European regulatory criteria and guidance

Lines of evidence ENDOCRINE ACTIVITY in mammals
Weight of Evidence In vitro mechanistic In vivo mechanistic
Strong ■Estrogen receptor binding-in silico IDs: 45, 51, 72, 75
■Estrogen receptor binding and agonist activity IDs: 3, 6, 8, 11–15, 17–18, 20–22, 42–44, 46, 48, 52, 62–65, 78, 81, 86–87
■Estrogen dependent cellular proliferation IDs: 7–6, 10, 15, 20, 48, 80
■Estrogen receptor dependent gene/protein expression increased IDs: 9–13, 15, 17–18, 20, 23, 48, 80
■Androgen receptor antagonist binding-in silico IDs: 75–76
■Androgen receptor binding and antagonist activity IDs: 19, 21–22, 43, 64, 78, 81, 87
■Steroidogenesis alteration IDs: 4–5, 87
■Thyroid hormone receptor binding-in silico ID: 75
■Thyroid hormone related gene expression decreased ID: 7
■Estrogen receptor dependent gene expression increased (adult and gestational exposure) IDs: 59, 83
■Uterus weight increase (adult exposure) IDs: 61–63, 86
■Uterus histopathology alteration (adult exposure) ID: 63
■Steroidogenesis gene/protein expression alteration (adult and gestational exposure) IDs: 55, 58, 83
■Estradiol level increase in female offspring (gestational exposure) ID: 59
■Testosterone level decrease in male (adult exposure) ID: 55
■Progesterone level increase in female offspring (gestational exposure) ID: 59
■Progesterone level decrease in female (adult exposure) ID: 83
■FSH level increase in male (adult exposure) ID: 55
■LH level increase in male (adult exposure) ID: 55
■T4 level increase (adult exposure) ID: 60
Moderate ■Thyroid hormone receptor activity alteration IDs: 7–8, 21, 64 ■Testosterone level increase in male offspring (gestational exposure) ID: 58
Weak   ■Weight increase of male androgen-dependent sex accessory tissues (adult exposure ID: 61
■Testosterone level decrease in female offspring (gestational exposure) ID: 59
No evidence for effect   ■Estradiol level alteration in male offspring (gestational exposure) ID: 58
■Estradiol level in female (adult exposure) ID: 83
■Testosterone fetal production alteration (gestational exposure) ID: 56
■FSH level alteration in female (adult exposure) ID: 83
■FSH levels alteration in male offspring (gestational exposure) ID: 58
■LH level alteration in male offspring (gestational exposure) ID: 58
■TSH level alteration (adult exposure) ID: 60