Human studies addressing exposure to PHTs and obesity (N=18)72 83
| Authors, year | Country | Study design, quality | Study objective | Source population | Sex and age | Sample size | Sample, compounds (DR) and method | Outcomes | Adjustment for confounding factors | Main findings |
| Stahlhut et al, 200728 | USA | Cross-sectional, 4 | To investigate the association between [urinary PHTs] and abdominal obesity and insulin resistance | General population, NHANES 1999–2002 | Male, >18 years | 1443 | Urine PHT metabolites MBP, MEP, MBzP, MEHHP, MEOHP, MEHP (>80%), MiNP (25%) HPLC-MS | WC | Age, race/ethnicity, family history of diabetes, dietary fat and caloric intake, physical activity, income, renal function, hepatic function, exposure to tobacco | MBzP, MEHHP, MEOHP and MEP positively associated with increased WC |
| Hatch et al, 200829 | USA | Cross-sectional, 5 | To investigate the association between [urinary PHT metabolites] and BMI and WC | General population, NHANES 1999–2002 | Male and female, 6–80 years | 4836 | Urine MEP, MEHP, MBzP, MBP, MEHHP, MEOHP (>80%), MCP, MNP, MOP (≤80%) HPLC-MS | BMI, WC | Age, gender, urinary creatinine, height, diet variables, physical activity, race/ethnicity, education, family income, education level, smoking, alcohol consumption, menopausal status, parity, TV/video/computer use | Urinary MBzP] positively associated with BMI and WC in men aged 20–59 years [Urinary MEP] positively associated with BMI and WC in adolescent girls [Urinary MEHP] inversely associated with BMI in adolescent girls and women aged 20–59 years |
| Lind et al, 201257 | Sweden | Cohort, 7 | To investigate the association between [serum PHT monoester] and measures of adiposity after 2 years | Subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors | Male and female, 70 years | 1016 | Serum MEHP, MEP, MiBP, MMP (>96%) LC-MS/MS | Fat mass (DXA and MRI) | Serum TC and TG, education, exercise, smoking | [Serum MiBP] positively associated WC, total FM, trunk FM, SAT after 2 years in women [MMP] positively associated with trunk fat mass and trunk:leg ratio after 2 years in women |
| Teitelbaum et al, 201230 | USA | Cohort, 7 | To investigate the association between [urinary PHT metabolites] and BMI and WC in children | Children from the Growing Up Healthy prospective cohort study | Male and female, 6–8 years | 387 | Urine MEP, MBP, MCPP, MBzP, MiBP, MEOHP, MECPP, MEHHP (>97%), MEHP (81%–90%) HPLC-MS | BMI, BMI z-score, WC after 1 year of PHT exposure measurement | Age at baseline, sex, hours of sedentary activity, day of week for reported sedentary activity, MET hours, total caloric intake, race, ethnicity, family income, parental education | [Urinary MEP] and [urinary sum of low molecular-weight PHTs] positively associated with BMI and WC in overweight girls after 1 year |
| Wang et al, 201375 | China | Cross-sectional, 6 | To investigate the association between [urinary PHT metabolites] and BMI and WC in school children | Obese, OW and normal weight (20:10:30) children selected from primary and middle schools in Shangai, China | Male and female, 8–15 years | 259 | Urine MEHP, MEOHP, MECPP, MEHHP, MBP, MiBP, MEP, MCMHP, MHBP, MMP, MCHP (≥94.6%) MBzP (38.6%) MiNP, MOP (0%) Sum MBP, MHBP, MiBP, MMP, MEP Sum MEHP, MECPP, MEHHP, MEOHP, MCMHP, MCHP, MBzP, RPUPLC-ESI-MS/MS | BMI, WC, normal weight, OW and OB defined according to age and sex-specific criterion (Working Group on Obesity in China) | Age, sex, urine PHT metabolites, urine specific gravity | MEHP and MEP positively associated with BMI and WC |
| Choi et al, 201467 | South Korea | Cross-sectional, 4 | To investigate the association between exposure to POPs and obesity | Participants recruited among subjects from a medical college in Seoul | Female, 6–14 years | 127 (58 controls, 69 obese) | Urine and serum MEP, DBP, DEHP, MEHP, PA, MBzP (NS) GC-MS | BMI (OB defined by BMI > p85) | None | MEP, DBP and PA positively associated with obesity |
| Song et al, 201421 | USA | Cross-sectional, 6, and cohort, 8 | To investigate the association between [urinary PHT metabolites] and weight change after 10 years | Adult female non-diabetic (control) population from NHS and NHSII | Female, 53–79 years | 977 | Urine PA, MEP, MBzP, Sum of butyl PHTs, DEHP metabolites, total PHTs (NS) HPLC-MS | BMI, weight change (kg) | Urinary creatinine, cohort origin, age, menopausal status, smoking, physical activity, alcohol consumption, AHEI and total energy intake | Higher [PHT metabolites] associated with modestly greater weight gain in a dose-dependent fashion |
| Hou et al, 201576 | Taiwan | Cross-sectional, 8 | To investigate the association between [urinary PHTs] and obesity and pubertal maturity among adolescents | Children and adolescents selected from primary schools in Tapei, Taiwan | Male and female, 6.5–15 years | 270 | Urine DEHP metabolites (MEHP (78.1%), MEOHP, MEHHP, MECPP (≥99.6%)) LMW PHT metabolites (MMP, MEP, MiBP, MnBP (≥94.8%)) MBzP (94.4%) HMW PHT (DEHP metabolites, MBzP (NS)) UPLC-MS/MS | BMI, WC, WHR, skin fold thickness, OB defined by BMI (criteria from Taiwan’s Health Promotion Administration and by the Ministry of Health and Welfare) | Age, gender, urinary creatinine | [Urinary PHT metabolites] positively associated with abdominal obesity (assessed by skinfold thickness, WC and WHR), in a dose–response manner |
| Medic et al, 201558 | Serbia | Cross-sectional, 5 | To investigate the association between [urinary DHEP and DEP] and BMI, WC, plasma lipids and lipoproteins | Volunteers randomly recruited during physical examinations at the Institute of Occupational Medicine of Novi Sad, Serbia | Female, 18–55 years | 103 | Urine MEP (24.3%) and MEHP (16.5%) GC-MS | BMI, WC | None | [Urinary MEHP] positively associated with WC |
| Petrovicova et al, 201659 | Slovakia | Cross-sectional, 6 | To investigate the association between [urinary PHTs], occupation, consumer practices and body composition | Occupationally exposed subjects and non-occupationally exposed from the general population of the Nitra Region in Slovakia | Female and male, >18 years | 129 (45 occupationally exposed subjects, 35 workers from plastic industry, 49 from the general population) | Urine MEHHP, MEOHP, MEHP, MiBP, MnBP (≥82.2%) Sum DEHP HPLC-MS | BMI, WC, FMI, FFMI, HC, WHR, WHtR, WC > 102 cm (male) or > 88 cm (female) | Gender, occupational exposure | [Urinary MEHP] inversely related to WHtR, BMI, WHR, HC and WC, and positively related to FFMI among women but not men |
| Yaghjyan et al, 201631 | USA | Cross-sectional, 6 | To investigate the association between [urinary PHTs] and individual characteristics, including BMI | General population, NHANES 2001–2012 | Female and male, > 18 years (non-obese, non-pregnant, and non-diabetic) | 6653 | Urine DEHP metabolites (MEHP, MEHHP, MEOHP, MECPP), %MEHP (ratio of MEHP to sum of secondary metabolites) (NS) HPLC-MS | BMI, OW (BMI 25.0–29.9) | Age, gender, race, smoking, alcohol use, cancer history, daily caffeine consumption, prescription medication, menopausal status, postmenopausal hormone use | [Urinary MEHP:MEHHP] and [urinary %MEHP] inversely associated with the presence of overweight |
| Hong et al, 201772 | Korea | Cross-sectional, 6 | To investigate the association between exposure to EDCs and insulin resistance and obesity in healthy, reproductive-aged women | Women recruited from the community health and service centre and Ewha Womans University Mokdong Outpatient Clinic | Female, 30–49 years | 296 | Urine MEHHP, MEOHP, MnBP (NS) HPLC-MS | BMI, WC | Age, urinary creatinine, smoking and alcohol status, TG, TC, HDL-C | [Urinary PHTs] not associated with BMI and WC |
| Kataria et al, 201737 | USA | Cross-sectional, 5 | To investigate the association between [urinary bisphenols and PHTs] and body mass in children | Children from the General Paediatric Clinic at Bellevue Medical Centre | Female and male, 10–13 years | 41 | Urine MMP, MEP, MBP, MiBP, MBzP, MCHP, MOP, MCPP, MIDP, MCNP, MNP, MIDP, MCOP, MEHP, MECPP, MEHHP, MEOHP, MCMHP, MHxP, MHpP (NS) HPLC-MS/MS | BMI | Urinary creatinine, gender, age, caloric intake, physical activity | [Urinary high molecular weight PHT metabolites] positively associated with BMI |
| Yang et al, 201786 | Mexico | Cross-sectional, 8 | To investigate the association between exposure to BPA and PHTs and obesity | Participants from the 22 year Early Life Exposure in Mexico to Environmental Toxicants cohort | Female and male, 8–14 years | 249 | Urine MEP, MBP, MCPP, MiBP, MBzP, MEHP, MEHHP, MEOHP, MECPP (94%–100%) LC-MS/MS | WC, BF (skinfold thickness), BMI z-score | Urine-specific gravity, mother’s age, BMI, years of schooling and smoking status, child’s age and gender | [Urinary MEHP] positively associated with WC and skinfold thickness, [urinary MEH] inversely associated with skinfold thickness among boys |
| Oktar et al, 201784 | Turkey | Cross-sectional, 1 | To investigate the association between [serum and urinary PHTs] and obesity | Patients from the research hospital of Mustafa Kemal University | Male and female, 17–62 years | 196 | Serum and urine DMP, DEP, DBP, DPP, BBP, DEHP, DOP, GC | BMI, WC | None | [Urinary and serum PHTs] positively associated with BMI and WC |
| Dong et al, 201785 | China | Cross-sectional, 5 | To investigate the association between [urinary PHT metabolites] and obesity | Participants from the Shangai Food Consumption Survey 2012 | Male and female, >18 years | 2330 | Urine MMP, MEP, MnBP, MiBP, MBzP, MEHP, MEOHP, MEHHP, MECPP, MCMHP LC-MS/MS | OB and OW defined by BMI, abdominal obesity (> 85 cm for men and > 80 cm for women) | OB: age, gender, education, marriage, smoking, total caloric intake calories, and total fat intake Abdominal obesity: age, marriage, education, smoking status, BMI, total caloric intake, and total fat intake. | [Urinary MMP, MEHHP, MECPP] associated with abdominal obesity; the association was stronger among young females |
| Lee et al, 201783 | South Korea | Cross-sectional, 6 | To investigate the association between [urinary PHTs] and demographic characteristics | Subjects randomly recruited from the population of the Korean National Human Biomonitoring Survey | Male and female, 18–69 years | 1870 | Urine MnBP, MiBP, MBzP, MCHP, MnOP, MEHP, MEOHP, MEHHP, MiNP, MiDP HPLC-MS | OB and OW defined by BMI | Urinary creatinine | [Urinary PHT metabolites] not associated with OB or OW |
| Shoaff et al, 201741 | USA | Cohort, 8 | To investigate the association between [urinary PHTs] and measures of adiposity in children | Participants from the Health Outcomes and Measures of the Environment | Male and female, 1 years | 219 | Urine MEP, MnBP, MiBP, MCPP, MBzP, MEHP, MEHHP, MEOHP, MECPP SumDEHP HPLC-MS/MS Measurements conducted six times, from 1 to 8 years | BMI, WC, %BF at the age of 8 years | Urinary creatinine, maternal age at delivery, race, marital status, insurance, income, education, parity, cotinine, depressive symptoms, midpregnancy BMI, food security, prenatal fruit/vegetable and fish consumption, prenatal vitamin use, child sex, and child age at the 8-year visit | [Urinary MBzP] inversely associated with adiposity; [urinary sum DEHP] at 1 and 5 years associated with decrease and increase in adiposity at 8 years, respectively; [urinary MEP] at 5 and 8 years associated with higher adiposity at 8 years |
AHEI, Alternative Healthy Eating Index; BBP, benzyl butyl phthalate; BF, body fat; BMI, body mass index; BPA, bisphenol A; DBP, dibutyl phthalate; DEHP, diethylhexyl-phthalate; DEP, diethyl phthalate; DMP, dimethyl phthalate; DOP, dioctyl phthalate; DPP, dipentyl phthalate; DR, detection rate; DXA, dual-energy X-ray absorptiometry; EDC, endocrine disrupting chemical; FFMI, fat-free mass index; FM, fat mass; FMI, fat mass index; GC-MS, gas chromatography–mass spectrometry; HC, hip circumference; HDL-C, high-density lipoprotein cholesterol; HMW, high-molecular-weight; HPLC-MS, high-performance liquid chromatography–mass spectrometry; HPLC-MS/MS, high-performance liquid chromatography-tandem mass spectrometry; LC-MS/MS, liquid chromatography–tandem mass spectrometry; LMW, low-molecular-weight; MBP, monobuthylphthalate; MBzP, monobenzyl phthalate; MCHP, mono-cyclohexyl phthalate; MCMHP, mono(2-carboxymethylhexyl) phthalate; MCNP, monocarboxylisononyl phthalate; MCOP, mnocarboxyisooctyl phthalate; MCP, mono-cyclohexyl phthalate; MCPP, mono (3-carboxypropyl) phthalate; MECPP, mono-(2-ethyl-5-carboxypentyl) phthalate; MEHHP, mono-2-ethyl-5 -hydroxyhexyl phthalate; MEHP, monoethylhexyl phthalic acid; MEOHP, mono(2-ethyl-5-oxohexyl) phthalate; MEP, monoethyl phthalate; MET, metabolic equivalent; MHBP, Mono-3-hydroxybutyl phthalate; MHpP, mono-2-heptyl phthalate; MHxP, mono-hexylphthalate; MiBP, mono-isobutyl phthalate; MIDP, mono-8-methyl-1-nonyl-phthalate; MiNP, mono-isononyl phthalate; MMP, mono-methyl phthalate; MnBP, Mono-n-butyl phthalate; MnOP, mono-n-octyl phthalate; MNP, mono-isononyl phthalate; MOP, mono-n-octyl phthalate; NHANES, National Health and Nutrition Examination Survey; NHS, Nurses’ Health Study; NHSII, Nurses’ Health Study II; NS, not stated; OB, obesity; OW, overweight; PA, phthalic acid; PHT, phthalate; POPs, persistent organic pollutant; RPUPLC-ESI-MS/MS, reversed-phase ultraperformance liquid chromatography–electrospray ionisation–tandem MS; SAT, subcutaneous adipose tissue; TC, total cholesterol; TG, triglycerides; UPLC-MS/MS, ultraperformance liquid chromatography–tandem mass spectrometry; WC, waist circumference; WHR, waist-to-hip ratio; WHtR, waist-to-height ratio.