Table 1.

Metabolic disturbances observed in animal studies following developmental exposure to bisphenol A.

Paper	Doses ($\mathrm{\mu }\mathrm{g}/\mathrm{kg}$)	Exposure window	Exposure route	Strain, species	Outcomes
(Cabaton et al. 2013)	0.025, 0.25, 25	GD8–PND16	Osmotic pump	CD-1 mice	Disrupted global metabolism ($\mathrm{♂}$) PND2, 21; significant doses: 0.025, 0.25, $25\mathrm{\mu }\mathrm{g}/\mathrm{kg}$
	1, 10	Perinatal	Water	S-D rats	Increased BW and visceral adipose tissue, abnormal lipid levels, lower adiponectin levels; significant doses: 1 and $10\mathrm{\mu }\mathrm{g}/\mathrm{kg}$
(García-Arevalo et al. 2014)	10	GD9–GD16	Subcutaneous	OF-1 mice	Increased BW and increased weight of fat pad mass increased hepatic triglyceride levels, alterations of mRNA gene expression of genes involved in lipogenesis and liver metabolism ($\mathrm{♂}$) PND196; significant dose: $10\mathrm{\mu }\mathrm{g}/\mathrm{kg}$
(Kabuto et al. 2004)	5, 10 ($\mathrm{\mu }\mathrm{g}/\mathrm{mL}$)	Embryonic/fetal and throughout lactation	Water	ICR mice	No effect on BW ($\mathrm{♂}$)
(Miyawaki et al. 2007)a	1, 10 ($\mathrm{\mu }\mathrm{g}/\mathrm{mL}$)	GD10–throughout lactation	Water	ICR mice	Increased BW ($\mathrm{♀}$, $\mathrm{♂}$) adipose tissue weight, total cholesterol levels ($\mathrm{♀}$) and triacylglycerol levels ($\mathrm{♂}$) PND31; significant doses: 1 and $10\mathrm{\mu }\mathrm{g}/\mathrm{kg}$
(Newbold et al. 2007a)	10, 100, 1,000	Perinatal	Subcutaneous	CD-1 mice	No effect on BW ($\mathrm{♀}$)
(Roepke et al. 2016)	50, 5,000	Embryonic day 18–21 and PND0–PND7	i.p to dams, subcutaneous to pups	FCDC rats	No effect on BW, decreased levels of adipoR1, no change in ER1, 2 or $\text{PPAR}\mathrm{\gamma }$ levels ($\mathrm{♀}$) PND50–60; significant doses: 50 and $5000\mathrm{\mu }\mathrm{g}/\mathrm{kg}$
(Rubin et al. 2016)	0.25, 2.5, 25, 250	Perinatal (P) or perinatal and peripubertally ($\mathrm{P}+\mathrm{P}$)	Osmotic pump	CD-1 mice	Increased BW (P $\mathrm{♀}$ and $\mathrm{P}+\mathrm{P}\mathrm{♀}$) PND28 and 35; elevated insulin levels (P $\mathrm{♀}$ and $\mathrm{P}+\mathrm{P}\mathrm{♀}$) PND196 and 238; and elevated glucose levels ($\mathrm{P}+\mathrm{P}\mathrm{♀}$) PND238; significant doses: 0.25 and $2.5\mathrm{\mu }\mathrm{g}/\mathrm{kg}$
(Ryan and Vandenbergh 2006)	2, 200	GD3-PND21	Gavage	C57/Bl-6 mice	No effect on BW ($\mathrm{♀}$, $\mathrm{♂}$)
(Ryan et al. 2010)	0.25	GD1–PND21	Diet	CD-1 mice	Increased BW and length that did not persist throughout adulthood ($\mathrm{♀}$, $\mathrm{♂}$) PND21; significant dose: $0.25\mathrm{\mu }\mathrm{g}/\mathrm{kg}$
(Somm et al. 2009)	70	GD6–PND21	Water	S-D rats	Increased BW PND1 ($\mathrm{♀}$, $\mathrm{♂}$), PND21 ($\mathrm{♀}$); increased pWAT and BAT mass, adipocyte hypertrophy and alterations of mRNA gene expression of genes involved in metabolism and lipogenesis PND21($\mathrm{♀}$); significant dose: $70\mathrm{\mu }\mathrm{g}/\mathrm{kg}$
(Susiarjo et al. 2015)	10, 10,000	Perinatal	Diet	C57BL/6 mice	Decreased BW PND1; increased BW, higher body fat content, and impaired glucose homeostasis ($\mathrm{♂}$) PND98–117; significant dose: $10\mathrm{\mu }\mathrm{g}/\mathrm{kg}$
(Tremblay-Franco et al. 2015)	0.25, 2.5, 25, 250	Perinatal	Osmotic pump	S-D rats	Metabolic changes in liver and serum composition ($\mathrm{♀}$, $\mathrm{♂}$) PND21, 50, 90, 140 and 200; significant doses: 0.25, 2.5, 25, and $250\mathrm{\mu }\mathrm{g}/\mathrm{kg}$
(van Esterik et al. 2014)b	3, 10, 30, 100, 300, 1,000, 3,000	Gestation and lactation	Diet	Hybrid C57BL/6J mice	Increased ($\mathrm{♂}$) and decreased ($\mathrm{♀}$) BW, decreased fat pad weights, adipocyte size (increased in $\mathrm{♂}$, not dose-dependent), and levels of serum triglycerides, leptin, and adiponectin ($\mathrm{♀}$) PND147 (effects were dose-dependent)
(Wei et al. 2011)	50, 250, 1,250	GD0–PND21	Oral gavage	Wistar rats	Increased body fat percentage ($\mathrm{♀}$, $\mathrm{♂}$), increased levels of triglycerides and size of adipocytes ($\mathrm{♂}$) PND189; significant dose: $50\mathrm{\mu }\mathrm{g}/\mathrm{kg}$
This study	0.5, 50	GD3.5–PND22	Water	F344 rats	No effect on BW. Increased plasma triglycerides, adipocyte density (decreased adipocyte size), and alterations of mRNA expression of genes involved in lipogenesis, adipocyte adiponectin signaling, and liver metabolism (e.g, increased levels of adipoR1, no change in ER1, 2, or $\text{PPAR}\mathrm{\gamma }$ levels) ($\mathrm{♀}$, $\mathrm{♂}$) PND22; significant doses: 0.5 and $50\mathrm{\mu }\mathrm{g}/\mathrm{kg}$

Note: Adipor1, adiponectin receptor 1; BAT, brown adipose tissue; BW, body weight; ER, estrogen receptor; FCDF, Fischer CDF; F344, Fischer 344; GD, gestational day; i.p, intraperitoneal; OF-1, Oncins France 1; PND, postnatal day; PPARγ, peroxisome proliferator-activated receptor gamma; pWAT, perigonadal adipose tissue; S-D, Sprague-Dawley. Significant doses are statistically significant changes compared with controls.

^aAnimals were challenged with a high-fat diet or fructose.

^bThe benchmark dose approach was used in this study.