Table 6.
Substance | Reference | Country | Population | Sample size | Biological materials | Measurement | Exposure assessment | Outcomes | Results | Adjustment factors |
---|---|---|---|---|---|---|---|---|---|---|
DEHP | Berman et al. (115) | Australia 1989–1992 (prenatal) | Mother–child pairs from the Raine Study | 387 | Maternal serum | LCMS/MS | Phthalate diesters | NAFLD at 17 years old ALT, AST, GGT | Mid-levels of prenatal exposures to MnBP were associated with a greater incidence of NAFLD. | Age, household income at birth, maternal education level at birth, duration of breast feeding, BMI z-score, height |
DEHP | Chen et al. (116) | USA 2017–2018 | NHANES adults | 1,450 | Urine | HPLC-ESI-MS/MS | Mean ± SD MECPP: 1.89 ± 0.03 ug/g MEOHP: 0.99 ± 0.03 ug/g MEHHP: 1.44 ± 0.03 ug/g MCiNP: 0.16 ± 0.02 ug/g MCiOP: 1.51 ± 0.04 ug/g MCiNP: 0.19 ± 0.03 ug/g | NAFLD prevalence | Higher prevalence of NAFLD is correlated with MECPP and MEHHP. There is no significant relationship between phthalates and liver fibrosis. | Age, sex, smoking status, education, race/ethnicity, physical activity, diabetes, blood pressure, BMI, total cholesterol levels |
DEHP | Fu et al. (90) | China 2018.7–8 | Children (5–14 years) | 1,006 | Serum | HPLC | Median DMP: 31.62 ng/mL | ALT, AST, TBIL | Serum DMP concentration and TBIL level were significantly positively correlated. | Age, address, gender |
DEHP | Li et al. (117) | USA 1999–2014 | NHANES participants | 17,878 (HIS-NAFLD) 8,487 (USFLI-NAFLD) | Urine | HPLC-ESI-MS/MS | 13 phthalates OR (95%CI) Urinary phthalates: 1.18(1.09–1.4) | NAFLD prevalence | Urinary phthalates were positively associated with NAFLD development. | Age, sex, race, education, family income-to-poverty ratio, marital status, employment, insurance, self-reported comorbidities, alcohol consumption, cigarettes smoking, leisure time physical activity, diet quality |
DEHP | Midya et al. (72) | France, Greece, Lithuania, Norway, Spain, UK 2021–2022 | Mother–child pairs from the Human Early-Life Exposome project | 1,108 | Serum | GC-MS/MS | 10 phthalates | ALT, AST, GGT and CK-18 of children | Decreased odds of liver injury were associated with high-molecular-weight phthalates. | Subcohort, maternal age, maternal prepregnancy BMI, maternal educational level, parity, child age, child sex |
DEHP | Yang et al. (118) | Korea 2012–2014 | Adults with subclinical hypothyroidism from KoNEHS | 2,308 | Urine | UPLC-MS | Geometric mean(95%CI) ug/L MEHHP: 3.02(2.97–3.06) EH 3.10(2.98–3.23) SCH MEOHP: 2.66(2.61–2.71) EH 2.76(2.64–2.89) SCH MECPP: 3.15(3.10–3.19) EH 3.22(3.11–3.33) SCH MBzP: 1.13(1.05–1.21) EH 1.02(0.84–1.20) SCH MnBP: 3.32(3.26–3.39) EH 3.35(3.22–3.48) SCH | Risk of NAFLD | The levels of phthalate metabolites in urine are positively associated with NAFLD in adults with subclinical hypothyroidism (SCH). | Age, gender, drinking, smoking, physical activity, monthly household income, education, marital status, clinical variables |
DEHP | Cai et al. (114) | USA 2003–2016 | NHANES adults (>20 years) | 4,206 | Urine | HPLC-ESI-MS/MS | 9 phthalates (MEOHP, MEP, MEHHP, MECPP, MnBP, MEHP, MiBP, MBzP, MCPP) | ALT, AST, GGT | Phthalates exposure was independently associated with NAFLD both in males and females. | Age, gender, education levels, race/ethnicity, marital status, family poverty income ratio, BMI, total cholesterol, survey circle, smoking status, physical activity, hypertension, alcohol consumption |
DEHP | Yang et al. (119) | Korea 2012–2014 | KoNEHS adults | 5,800 | Urine | UPLC-MS | GM ± SE MEHHP: 2.922 ± 0.011 ug/L MEOHP: 2.571 ± 0.011 ug/L MECPP: 3.059 ± 0.010 ug/L MnBP: 3.211 ± 0.012 ug/L MBzP: 1.047 ± 0.015 ug/L | NAFLD prevalence | The prevalence of NAFLD was associated with urinary levels of MEHHP, MEOHP, MECPP, MBzP, MnBP compared to the reference group. | Age, gender, smoking, drinking, exercise level, marital status, education level, socioeconomic status. |
DEHP | Yu et al. (120) | USA 2007–2016 | NHANES adults (≥20 years) | 6,046 | Urine | HPLC-ESI-MS/MS | 15 phthalate metabolites Median ΣDEHP: 3.1 ug/mmol | ALT, AST, ALP, TBIL | Positive dose–response relationships between urinary phthalate metabolites and ALT or AST, ΣDEHP and GGT were observed. Significant positive associations of ΣDEHP with TBIL were found after adjusting for potential confounders. | Age, sex, race/ethnicity, education level, the ratio of family income to poverty, physical activity, alcohol consumption, medications |
DEHP | Milošević et al. (121) | Serbia | Adults (18–50 years) | 305 | Urine | GC-MS | 10 phthalates metabolites mean ± SD all phthalates: 304.55 ug/g MEP: 132.2 ± 188.6 ug/g MEHP: 80.36 ± 96.27 ug/g | ALT, AST, GGT | Phthalates exposure was associated with elevated AST levels. ALT and AST values were increased in MEP exposed while GGT levels were enhanced in MEHP exposed. | Obesity, diabetes |
DEHP | Milošević et al. (104) | Serbia 2015–2016 | Male participants (18–55 years) | 102 | Urine | GC-MS | MEP, MEHP, MPP, MiAP, MnAP, MCHP, MBzP, MOP, MBP | ALT, AST, GGT | Significant increment in transaminase serum levels was observed in MEP-positive normal weight sub-group. The phthalates exposure may be related to statistically significant ALT and AST serum levels increment. | NR |
UPLC, ultra-high-performance liquid chromatography; HPLC, high-performance liquid chromatography; HPLC-MS, high-performance liquid chromatography-tandem mass spectrometry; UPLC-MS, ultra-high-performance liquid chromatography mass spectrometry; LC-MS, liquid chromatography-mass spectrometry; LC-MS/MS, liquid chromatography coupled to tandem-mass spectrometry; HPLC-ESI-MS/MS, High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry; GC-MS, gas chromatograph-mass spectrometry; GC-MS/MS, gas chromatography coupled to tandem mass spectrometry.