Table 3.
Effects of EDCs on Diabetes Mellitus and Obesity
| EDC | Animal | Sex | Exposure Period | Dosage, Route | Age at Analysis | Obesogenic/Diabetogenic | Endpoints | Ref |
|---|---|---|---|---|---|---|---|---|
| BPA | Wistar rats | M/F | E0, P21 | 50, 250, 1250 μg/kg/d, oral, gavage | 13–26 wk | Obesogenic; diabetogenic; exacerbates obesogenic and diabetogenic action of HFD; nonmonotonic | Body weight, glucose tolerance, insulin resistance, plasma insulin, β-cell mass, β-cell mRNA expression, lipid homeostasis | 139 |
| BPA | S-D rats | M/F | E6–P21 | 1 mg/L in drinking water | P21 | Obesogenic | Body weight, fat weight, mRNA expression | 241 |
| BPA | CF-1 mice | M/F | E11–17 | 2.4 μg/kg/d, oral, food | P0, P22, and P26 | Obesogenic | Body weight at weaning, age at vaginal opening, and interval between vaginal opening and first vaginal estrus | 237 |
| BPA | S-D rats | M/F | 10-wk prebreeding exposure, mating, and E0–P21 | 50 and 500 mg/kg/d, dietary concentrations | F0 to F3 generations | Weight reduction in all generations | Body weight | 250 |
| BPA | Long-Evans rats | M | E12–P21, P21–P90 | 2.4 μg/kg/d, oral, dissolved in corn oil | 90 d | Obesogenic in offspring, no increase in weight in adults | Body weight | 236 |
| BPA | ICR/Jcl mice | M/F | E0–P21 | 20 μg/kg/d, sc injection | P21, 10 wk | No change in weight | Body weight | 248 |
| BPA | Wistar rats | M | Gestation and lactation | 50 μg/kg/d, oral gavage | 3 wk | Diabetogen | Weight, serum insulin, insulin resistance, DNA methylation, hepatic glucokinase expression | 310 |
| BPA | C57BL/6 mice | M | Acute administration, adulthood | 50 μg/kg, oral, water | 6 mo | Possible diabetogenic | Hepatic glucokinase activity | 307 |
| BPA | C57BL/6J mice | M/F | E1 lactation | 0, 3, 10, 30, 100, 300, 3000 μg/kg/d, oral, food | 23 wk | Decreased weight in females, sex-dependent small alterations in energy homeostasis | Body weight, organ weight, hormones in plasma, glucose tolerance, locomotor activity, histopathology | 249 |
| BPA | CD-1 mice | M | E8–P16 | 0.025, 0.25, 25 μg/kg/d, osmotic pumps | P2 and P21 | Possible diabetogen | Global metabolism by metabolomics | 309 |
| BPA | CD-1 mice | M | 28 d, adulthood | 0, 5, 50, 500, 5000 μg/kg/d, oral, food contamination | 10 wk | Possible diabetogen and obesogen | Hepatic transcriptome, liver triglyceride accumulation | 306 |
| BPA | OF-1 mice | M/F | E9–E16 | 10, 100 μg/kg/d, sc injection | Mothers at E16–E18 and 4 mo after delivery, offspring at 3 and 6 mo old | Diabetogenic in mothers and offspring; obesogenic in mothers | Glucose tolerance; insulin sensitivity; insulin, leptin, triglycerides and glycerol plasma levels; pancreatic β-cell function; changes in body weight; measurement of η-cell mass and proliferation | 138 |
| BPA | OF-1 mice | M | 4 d, adulthood | 10, 100 μg/kg/d, sc injection | 8–12 wk, adulthood | Diabetogenic | Insulin sensitivity, glucose tolerance, plasma insulin and glucose levels, pancreatic β-cell function | 172 |
| BPA | OF1 mice | M | 8 d, adulthood | 100 μg/kg/d, sc injection | 8–12 wk | Diabetogenic | Global metabolism, glucose tolerance, insulin resistance, plasma insulin, insulin secretion, Akt phosphorylation in skeletal muscle and liver | 244 |
| BPA, DEHP, DBP | Harlan S-D rats | M/F | E8–E14 | Mix of 50 BPA, 750 DEHP, and 66 DBP mg/kg/d, ip injection | F1 generation, F3 generation | Obesogenic in F3 generation | Body weight, abdominal adiposity | 262 |
| BPA, DES | CD-1 mice | M/F | E9–E18 | 5, 50, 500, 5000, 50 000 μg/kg/d BPA, or 0.1 μg/kg/d DES, oral | 3–19 wk | Obesogenic, diabetogenic, nonmonotonic | Body weight, fat weight, glucose tolerance, insulin resistance, plasma insulin, plasma leptin, plasma adiponectin | 140 |
| BPA, DES | CD-1 mice | M/F | E0 to weaning | 1 μg/kg/d DES, 0.25 μg/kg/d BPA, oral, feeding | P21–P15 wk | No increase in weight | Body weight, length, and fat and lean composition; food intake; glucose tolerance test | 246 |
| BPA, EE | C57/Bl-6 mice | M/F | E3–P21 | 2 and 200 μg/kg/d BPA, 5 μg/kg/d EE, oral, gavage | P21 | No increase in weight | Body weight, anxiety | 247 |
| BPA, estrone | S-D rats | M/F | E6 throughout lactation | 0.1 mg/kg/d BPA, 1.2 mg/kg/d estrone, oral, drinking water | 4 d to 4–6 mo | Obesogenic | Analysis of body weight, pattern of estrous cyclicity, and uterotrophic assay | 240 |
| BPA, EQ, EB, DPN, PPT | Long-Evans rats | M | P0–P3 | 50 μg EB, 1 mg/kg; PPT, 1 mg/kg; DPN, 10 mg/kg; EQ, 50 μg/kg; BPA, sc injection | P68 | Obesogenic | Body weight | 239 |
| BPA HFD | ICR mice | M/F | E13–E16 | 0.2 and 3 mg/kg/d, oral, drinking water | 1 mo | Obesogenic | Body weight, fat weight, serum leptin and lipids | 238 |
| BPA HFD | OF-1 mice | M | E9–E16 | 10 μg/kg/d, sc injection | 17–28 wk | Obesogenic, diabetogenic | Body weight, fat weight, glucose tolerance, insulin resistance, plasma insulin, insulin secretion, mRNA expression | 242 |
| DDT | C57BL/6J mice | F | E11.5–P5 | 1.7 mg/kg body weight | Up to 6 mo | Obesogenic, diabetogenic | Body composition, energy homeostasis, metabolic parameters, glucose tolerance. Energy balance, metabolic consequences of HFD | 259 |
| BPA, TCDD, PCB-153, DEHP | C57BL/6J mice | M/F | Before gestation, during gestation, lactation, combined with standard diet and HFD | Tolerable daily intake of each component of the mixture, oral in pellets | 10–12 wk | Diabetogen | Weight, hepatic gene expression, plasma leptin, insulin and cholesterol, glucose and insulin tolerance | 313 |
| DEHP | Wistar rats | M/F | Gestation and lactation | 1.25, 6.25 mg/kg/d, oral gavage | 3, 15, 26 wk | Diabetogenic | Weight, glucose and insulin tolerance, β-cell mass and function | 312 |
| DES | CD-1 mice | M/F | P1–P5 | 1 μg/kg/d, 1 mg/kg/d, sc injections | 2, 6 mo | Obesogenic | Analysis of body weight and fat pads; serum levels of leptin, adiponectin, IL-6, insulin, and triglycerides | 1277 |
| DES | C57BL/6J | M/F | E12–P7 | 0.01, 0.025, 0.05, 0.1 mg/kg/d, oral, gavage | 8 wk | Obesogenic | Body weight, fat weight, cholesterol, triglycerols, glucose | 1278 |
| DDT | Harlan S-D rats | M/F | E8–E14 | 50, 25 mg/kg/d, ip injection | 10 mo, F1 generation, F3 generation | Obesogenic in F3 generation | Body weight, abdominal adiposity | 263 |
| FM 550 | Wistar rats | F | E8–P21 | 100, 1000 μg/d, oral, in pellets | 21 d, 17 wk | Obesogenic, cardiovascular disruptor | Serum T4, hepatic carboxylesterase activity, body weight, glucose tolerance, heart wall thickness | 565 |
| MEHP | C57BL/6J mice | M/F | E12–P7 | 0.5, 0.25, 0.05 mg/kg/d, oral, gavage | 60 d | Obesogenic, diabetogenic, nonmonotonic | Weight, fat weight, blood glucose, cholesterol, triacylglycerols, mRNA expression adipogenic genes | 142 |
| PCB-126 | Wistar rats | M | E7–P21 | 100 mg/kg/d, oral, food | 20 mo | Obesogenic | Neurobehavior, body weight | 256 |
| PCB-153 | C57BL/6J mice | M | 12 wk, adulthood | 50 mg/kg × 4, ip injection | 12 wk | Exacerbates obesogenic action of HFD | Body weight | 1279 |
| PFOA | CD-1 mice | F | E1–E17 | 0, 0.01, 0.1, 0.3, 1, 3, 5 mg/kg/d, oral, gavage | 15–16 wk, 42, wk, 70–74 wk | Obesogenic; nonmonotonic | Body weight, serum, insulin, leptin, fat weight | 141 |
| PFOA | CD-1 mice | F | 17 d, adulthood | 1 mg/kg/d, oral, gavage | 10 wk | No change in weight | Body weight | 141 |
| PFOS | CD-1 mice | M/F | Gestation and lactation | 0, 0.3, 3 mg/kg, oral gavage | P21 and P63 | Diabetogenic | Fasting glucose and insulin levels, glucose tolerance | 304 |
| PFOS | CD-1 mice | M | 3, 7, 14, 21 d, adulthood | 0, 1, 5, 10 mg/kg/d, oral gavage | 8–12 wk | Hepatic steatosis, possible diabetogenic | Histology of liver, hepatic liver metabolism | 304 |
| POPs | CB57BL/6J | M | Adulthood | Different diets with farmed salmon fillets, with different POP concentrations, oral, food | Adulthood | Diabetogenic; obesogenic | Insulin and glucose tolerance, fat distribution, mRNA levels of target genes | 303 |
| POPs, PCDDs, PCDFs, non-ortho-PCBs, mono-ortho- substituted PCBs, organochlorine pesticides | S-D rats | M | 28 d, adulthood | Organochlorine pesticides, 0.36–2.63 ng/g diet; DDTs, 0.13–3.57 ng/g diet; PCDDs, 0.11–1 pg/g diet; PCDFs, 0.32–0.99 pg/g diet; non-ortho-substituted PCBs, 0.83–23.7 pg/g diet; mono-ortho-substituted PCBs, 4.30–1314.35 pg/g diet; PCBs, 0.07–2.35 ng/g diet, oral, food | Adulthood | Diabetogenic; obesogenic | Insulin sensitivity, hepatic lipid homeostasis and mRNA levels of target genes, glucose uptake, daily energy intake, quantification of body weight and visceral fat | 285 |
| TBT | KM mice | M | From puberty once every 3 d over 45 d | 0.5, 5, 50 μg/kg/d, oral, gavage | 45 d after treatment, adulthood | Obesogenic | Body weight; fat mass; plasma insulin, leptin, adiponectin, and resistin levels; histological liver changes; levels of hepatic adiponectin and resistin | 1280 |
| TBT | C57BL/6J mice | M/F | E12–E18 | 0.05–0.5 mg/kg/d, ip injection | P1–P10 wk | Obesogenic | Changes of body weight, changes of adiposity in liver, testis and inguinal adipose and mammary adipose depots, quantitative analysis RXR:PPARγ target genes | 184 |
| TBT TBBPA | Swiss mice | NS | Single dose | 40 mg/kg, 2.1 g/kg, oral gavage, sc injection | 1 d | Possible metabolic disruptor | T3-independent transcription of Mc4r and Trh transcription | 252 |
| TBT TBBPA | Swiss mice | NS | E6 to delivery, for 7 d from E12 | 0.5 mg/kg/d 150 mg/kg/d, oral gavage | 2 d | Possible metabolic disruptor | T3-independent transcription of Mc4r and Trh transcription | 252 |
| TBT, ROSI | C57BL/6J mice | M/F | E16 | 0.1 mg/kg TBT, 1 mg/kg ROSI, oral, gavage | 8 wk | Obesogenic | Effects of TBT on stem cell proliferation, adipose, bone and cartilage differentiation | 251 |
| TCDD | C57BL/6J mice | M | Single dose, 4 wk old | 100 μg/kg/d, oral, gavage | 4–5 wk | Possible metabolic disruptor | Changes in body weight, analysis of intestinal disaccharide activity, gene and protein expression of intestinal glucose transporters, glucose tolerance test | 1281 |
| TCDD | Short-hair guinea pig | M | Single injection, 4–6 wk old | 0.01, 0.03, 0.1, 0.3, 1.0 μg/kg/d, ip injection | 0.25, 0.5, 1, 5, 10 and 28 d after single injection | Possible diabetogenic | Measurement of glucose uptake in pancreas, adipose tissue, liver and brain | 168 |
| TCDD | S-D rats | M | Single injection | 25, 125 μg/kg/d, ip injection | 1, 2, 4, 8, 16, 28 d after 125 μg/kg dose, 32 after 25 μg/kg dose | Possible metabolic disruptor | Changes in body weight, measurement of liver PEPCK and E-6-Pase activity, mean time to death | 1282 |
| TCDD | S-D rats | M | Single injection | 1 μg/kg/d, ip injection | 24 h after single injection | Diabetogenic | Pancreatic insulin content and release, pancreatic glucose uptake and protein levels of GLUT-2, plasma insulin, triglycerides, free fatty acids, and leptin levels | 286 |
| TCDD | C57BL/6J mice | M | Single injection, 8 wk old | 10 μg/kg/d, ip injection | 8 wk, adulthood | Diabetogenic | Glucose tolerance test, pancreatic insulin release | 287 |
Abbreviations: DPN, diarylpropionitrile; EB, estradiol benzoate; EE, ethinyl estradiol; EQ, equol; F, female; FM, Firemaster; HFD, high-fat diet; ip, intraperitoneal; M, male; PEPCK, phosphoenolpyruvate carboxykinase; PPT, propyl pyrazole; ROSI, rosiglitazone; sc, subcutaneous; S-D, Sprague-Dawley.