Table 1 (Original):

Mechanisms of action from the toxicological literature and findings from the epidemiological literature supporting effects of endocrine-disrupting chemicals on breastfeeding

Group	Example / Subgroup	Potential Mechanism of Toxicity in Relation to Mammary Gland Development and Lactation	Overview of Epidemiologic Evidence of Association with Breastfeeding
Per - & polyfluoroalkyl substances (PFAS)	PFOA	• PPARα activation (28, 29) • Impaired mammary gland differentiation, lobular alveoli development, epithelial involution (23–27, 30) • Suppression of prolactin and placental lactogen signaling (31) • Alterations in milk protein gene expression (23) • Transgenerational impacts on mammary gland development (24)	• Epidemiologic studies generally support an association of greater PFAS with shorter duration of breastfeeding (19–21) • One study suggests that low level exposures to specific, less well-studied PFAS, may increase breastfeeding duration (22)
Halogenated aromatic hydrocarbons	TCDD	• AhR activation (48) • Reduced mammary gland size, epithelial elongation, branching, terminal end bud development, and milk production (41, 42, 44, 47)	• To our knowledge, the influence of dioxins and dibenzofurans on breastfeeding have not been characterized in the epidemiologic literature. • Associations of PCBs with breastfeeding duration are mixed (35–38) • One study observed no association of PBDEs with either initiation of duration of any or exclusive breastfeeding (37)
	PCDFs	• AhR activation (48)
	PCBs	• Dioxin-like PCBs activate the AhR (48)
	PBDEs	• Bind, but do not activate, the AhR (49) • Disrupt mammary gland development, including β-catenin signaling (50, 51)
Organochlorine Pesticides (OCPs)	DDT	• ER agonist and AR antagonist (66) • Enhanced mammary gland development in pubertal rats (41)	• DDT exposure is generally associated with shorter duration of breastfeeding (36, 58, 59) • Some studies observe longer duration of breastfeeding (38) or no association (60, 61) with exposure to DDT or its breakdown products
Phthalates and Bisphenols	BBP, DEHP	• Impaired mammary gland (72) • BBP increases the proliferative index and expression of cell proliferation genes in mammary tissue (73, 74) • DEHP increases cell proliferation and number of alveolar buds (75) • Mammary gland effects are not observed at environmentally-relevant concentrations (76)	• Epidemiologic investigations of the influences of phthalates or BPA and its substitutes on breastfeeding are sparse • Limited epidemiologic evidence suggests no association of phthalates with breastfeeding duration (69) and shorter duration of any breastfeeding with greater BPA exposure (71)
	BPA, BPS	• ER agonist (77, 78) • Accelerated mammary gland development (e.g., branching, duct development, mammary epithelial cell proliferation) (79–82) • Reduced mammary gland differentiation, milk yield, lipid fraction, and protein synthesis (83, 84) • Altered ERα and prolactin signaling (85–87)

Table Abbreviations: AhR = Aryl hydrocarbon receptor; AR = Androgen receptor, BBP= N-butyl benzyl phthalate, DDT = Dichlorodiphenyltrichloroethane, DEHP = Diethylhexyl phthalate, ER = Estrogen receptor, PBDEs = Polybrominated diphenyl ethers, PCBs = Polychlorinated biphenyls, PCDFs = Polychlorinated dibenzofurans, PFOA= Perfluorooctanoic acid, PPARα = Peroxisome proliferator-activated receptor-alpha, TCDD = 2,3,7,8-tetrachlorodibenzo-p-dioxin