Endocrine disrupting chemicals in mixture and obesity, diabetes and related metabolic disorders

Table 1 Chemicals, sources and routes of exposure, examples, and some demonstrated metabolic effects

Chemicals	Sources	Examples	Some demonstrated metabolic effects
Alkylphenols	Lubricating oil additives; detergents; emulsifiers, pesticides; plastics Exposure occurs via water drinking and food consumption[67]	NP	Estrogenic activities[68]
Dioxins	Byproducts of industries from incomplete combustion; release during natural events such as wood burning and volcanic eruption Diet is the main route of exposure[69]	TCDD	Hepatic steatosis[70] and fibrosis[71]; increased adipocyte differentiation (in vitro)[72]
Flame retardants	Used in electronic equipment, furniture, plastics…and then, present in dust, air and soil Dermal exposure is a significant route of exposure[73]	Penta-BDE	Decrease in glucose oxidation[74]
Organotin compound	Used as biocide in anti-fouling paint, heat stabilizer in Poly Vinyl Chloride Exposure mainly by consumption of seafood[75]	TBT	Induction of adipocyte differentiation[76]; increase of body weight and hepatic steatosis[77]; transgenerational effects on fat depots and hepatic steatosis[39]
Phenolic derivatives	Plastic components, cosmetics, disinfectants, thermal paper receipts Food and water drinking are the major routes of exposure[78]	BPA, BPS	Estrogenic activities[79]; alteration of pancreatic β cell functions and hepatic insulin signaling (BPA)[47]; induction of lipid accumulation and differentiation (in vitro, BPS)[80]
Pesticides	Due to their persistence, accumulation in soils and sediments; bioaccumulation throughout the food chain	DDT and its metabolite	Alteration of systemic glucose homeostasis and hepatic lipid metabolism[83]; Glucose intolerance, hyperinsulinemia, dyslipidemia and altered bile acid metabolism[84]
	Processing of agriculture products (banned in Europe); Dietary sources[81] as well as inhalation and dermal routes of exposure[82]	Atrazine (C8H14ClN5)	Increased body weight, intra-abdominal fat and insulin resistance[85]
Phthalates	Plastic components, cosmetics, medical equipment; Exposure mainly derives from dietary sources for high molecular weight phthalates (e.g., DEHP) and non-dietary sources for low molecular weight phthalates (e.g., DBP)[86]	DBP, DEHP	Anti-androgenic effects[87]; Transgenerational inheritance of obesity[88]; Increased adipocyte differentiation[89]
PCBs	Synthetic compounds now banned but previously used, in particular, in electrical capacitors; still release in environment due to their persistence Food consumption contributes over 90% of total exposure[90]	PCB153 (C12H4Cl6), PCB170 (C12H3Cl7), PCB187 (C12H3Cl7) (non dioxin-like); PCB126 (C12H5Cl5), PCB77 (C12H6Cl4) (dioxin-like)	Increased adipocyte differentiation (in vitro); increased body weight, adipocyte hypertrophy[72]; increased hepatic steatosis and visceral adiposity in the context of a lipid-enriched diet[91]
PAH	Byproducts of incomplete combustion of organic compounds (cigarette smoke, wood burning, overcooked meat…) Contamination primarily through inhalation and consumption of certain foods[92]	B[a]P	Carcinogenic Alteration of estrogen metabolism in human mammary carcinoma-derived cell lines[93] Inhibition of lipolysis, increased fat accumulation and weight gain[94]
PFAA	Water and oil repellent; used for treatments of clothing, insulation and fire-fighting foams Oral and dermal exposure[95]	PFOA	Elevated serum leptin and insulin; overweight after in utero exposure[96]

PAH: Polycyclic aromatic hydrocarbon; PFAA: Perfluoroalkyl acids; PCBs: Polychlorobiphenyls; Np: Nonylphenols, C₁₅H₂₄O; DBP: Dibutyl phthalates, C₁₆H₂₂O; BPA: Bisphenol A, C₁₅H₁₆O₂; BPS: Bisphenol S, C₁₂H₁₀O₄S; TCDD: 2,3,7,8-tetrachlorodibenzo-p-dioxin, C₁₂H₄Cl₄O₂; Penta-BDE: Pentabrominated diphenyl ethers, C₁₂H₅Br₅O; TBT: Tributyltin, (C₄H₉)₃Sn; DDT: Dichlorodiphenytrichloethane, C₁₄H₉Cl₅; DDE: p,p′-dichlorodiphenyldichloroethylene, C₁₄H₈Cl₄; DEHP: Diethyl hexyl phthalate, C₂₄H₃₈O₄; B[a]P: Benzo[a]pyrene, C₂₀H₁₂; PFOA: Perfluorooctanoic acid, C₈HF₁₅O₂.