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Table 2 Summary of 38 studies that met the criteria for data extraction and estimated intake associated with statistically significant endpoints, grouped by population sampled

From: Role of epidemiology in risk assessment: a case study of five ortho-phthalates

Population sampled Significant endpoint Significant outcome Parent phthalate Estimated phthalate intake a Lower concentration statistically significant Reference
Women Number of ovarian antral follicles Decreased DEHP 0.03–0.25b 1.63 μg/L-13.5 μg/L [39]
Decreased DIBP 0.13–0.19c 10.21 μg/L
Decreased DBP 0.24–0.42 12.79 μg/L
Glucose levels Decreased DIBP 0.20 10.7 μg/L [38]
Thyroid hormone T4 Decreased DBP 0.20 9.6 μg/g CRE [55]
Free thyroid hormone T4 Decreased DEHP 0.53–1.80 1.69 μg/L-13.4 μg/L [56]
Thyroid hormone T4 and free T4 Decreased DBP 2.86 9.6 μg/g CRE [49]
Total number of oocytes, fertilized oocytes, mature oocytes, top quality embryos Decreased DEHP 0.23–1.39 0.02 uM-0.12 uM [57]
Total number of fertilized oocytes, mature oocytes, top quality embryos Decreased DBP 0.24 12.7 uM
Trophoblast differentiation genes Decreased DiBP 0.27 14.2 μg/L [58]
Decreased DBP 0.71 38 μg/L
Decreased DEHP 4.21 221.2 μg/L
Body mass index and waist circumference Increased DBP 0.30 12.26 μg/g [59]
Body mass index Increased DEHP 0.56 1.49 μg/g CRE
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Increased DEHP 1.56 12.51 μg/L [60]
Serum inhibin Decreased DEHP 2.04 5.44 μg/g CRE [61]
Gestational age Shorter DEHP 2.46 18.36 μg/L [62]
Longer DEHP 2.56–4.20 1.1 μg/L-5.1 μg/L [63]
C-section Increased likelihood DEHP 2.56–4.20 1.1 μg/L-5.1 μg/L [63]
Mothers (3 T) Serum steroid hormone binding globulin Increased BBP 0.06 3.16 μg/L [50]
Increased DBP 0.63 33.4 μg/L
Serum dehydroepiandrosterone sulfate Decreased DBP 0.63 33.4 μg/L
Social problems Increased BBP 0.07–0.23 3.2 μg/g [64]
Delinquent and externalizing behavior Increased DEHP 2.36 0.17 µmol/g CRE (sum DEHP)
Internalizing and externalizing problems Increased DEHP 6.27 16.7 μg/g CRE
Motor development Delayed DIBP 0.17 9.3 μg/L [65]
Psychomotor development index Decreased DIBP 0.17 9.3 μg/L
Clinically withdrawn behavior and internalizing behavior Increased BBP 0.36 19 μg/L
Psychomotor and mental development index Decreased DBP 0.71 38 μg/L
Clinically withdrawn behavior Increased DBP 0.71 38 μg/L
Full scale IQ, perceptual reasoning, processing speed, verbal comprehension and working memory Decreased DIBP 0.36 19 μg/L [36]
Decreased DBP 1.5 79.8 μg/L
Perceptual reasoning Decreased BBP 0.56 30 μg/L
Mental and psychomotor development indices Decreased in boys DBP 0.38 16.9 μg/g CRE [66]
Psychomotor development index Decreased in boys DEHP 2.7 13.2 μg/g CRE
Body mass index z-score Decreased in girls DEHP 1.77 0.128µM [67]
Mothers (2 T) Masculine play behavior Decrease DIBP 0.08 4 μg/L [52]
Decrease DEHP 0.38–0.88 1.4–4.7 μg/L
Internalizing behavior Increased BBP 0.26 12.8 μg/L [68]
Increased DBP 0.68 33.1 μg/L
Emotional symptom score and relationship problems Increased DBP 0.68 33.1 μg/L
Eczema Increased DIBP 0.51 25 μg/L [53]
Attention deficit hyperactivity disorder Increased DEHP 2.66 0.21 µM [69]
Mothers (1 T) Anogenital distance Shorter DEHP 0.66–0.80 2–6.1 μg/L [70]
Children (4–9 yo) Thyroid hormone T3 and free T3 Decreased in girls BBP 0.10 3.3 μg/L [71]
Decreased in girls DBP 1.97 63 μg/L
Decreased in boys DBP 2.34 75 μg/L
Children (12 yo) Height standard deviation Decreased in obese pubertal children DEHP 0.18 0.6 μg/g CRE [72]
Insulin sensitive index Increased in obese pre-pubertal children DEHP 0.19 0.27 μg/g CRE
Waist circumference Decreased in obese pre-pubertal children DEHP 0.19–0.35 0.27–1.24 μg/g CRE
Puberty Delayed in obese pre-pubertal children DEHP 0.19–0.35 0.27–1.24 μg/g CRE
Waist to hip ratio Increased in obese pre-pubertal children DEHP 0.23 0.76 μg/g CRE
Children (8–14 yo) Estrogen, testosterone and free testosterone Decreased DIBP 0.18 7.02 μg/L [50]
Free testosterone Decreased DEHP 1.52 3.48 μg/L
Serum steroid hormone binding globulin Increased DEHP 1.52–5.09 3.48–29 μg/L
Children (8 yo) Puberty Delayed in girls BBP 0.19 6.2 μg/L [73]
Delayed in girls DBP 1.56 50 μg/L
Delayed in girls DEHP 4.63 74 μg/L
Children (8–10 yo) Obesity Increased in boys DBP 0.95 30.4 μg/L [74]
Decreased in girls DEHP 1.72–4.31 3.3–32 μg/L
Children (6–19 yo) Albumin/creatinine ratio Increased DEHP 1.60 0.1 µM [75]
Systolic blood pressure Increased DEHP 3.20 0.166 µM [76]
Children (12–19 yo) Thyroid hormone T3 Increased DEHP 2.2–2.89 5.76–10.3 μg/g CRE [77]
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Increased DEHP 2.76 0.17 µM [78]
Men Sperm motility and concentration Decreased DBP 0.19 10.6 μg/L [48]
Decreased DBP 0.38   [79]
Sperm motility Decreased BBP 0.25 13.4 μg/L [79]
Semen quality Decreased DEHP 242.55 20.16 μg/L [47]
Testosterone, free testosterone, free androgen index Decreased DEHP 0.40–2.13 1.3–15.9 μg/L [80]
Serum steroid hormone binding globulin Increased DEHP 0.41 1.3 μg/L
Testosterone, estrogen, free androgen index Decreased DEHP 0.99 3.18 μg/L [81]
Testosterone/estrogen ratio Increased DEHP 0.99 3.18 μg/L
Thyroid hormone T3 and free thyroid hormone T4 Decreased DEHP 0.99 3.18 μg/L [82]
Thyroid stimulating hormone Decreased DEHP 242.55 21 µM [47]
Men and women Body mass index and waist circumference Increased BBP 0.58 30.9 μg/L [51]
Decreased DEHP 13.75 44 μg/L
Body mass index Increased DBP 0.72 38.4 μg/L
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Increased DEHP 3.16 18.51 μg/L
Thyroid hormone T4 Decreased DEHP 1.48–1.97 5.43–9.84 μg/g CRE [77]
Thyroid stimulating hormone Increased DEHP 1.97 9.84 μg/g CRE
  1. a In microgram per kilogram of body weight per day. See Supplemental Materials
  2. b For DEHP, a range is given when more than one metabolite was statistically significant for an endpoint
  3. c A range is given when statistical significance was observed at one or more tertile/quartiles
  4. d Q quartile
  5. Abbreviations: CRE creatinine; DEHP diethylhexyl phthalate; DBP dibutyl phthalate; BBP butylbenzyl phthalate; DIBP diisobutyl phthalate; IQ intelligence quotient; 1 T, 2 T, 3 T first, second and third trimester; yo year-old