Table 1.
Human studies on the association between the systemic levels of oxybenzone (BP-3)/octinoxate (OMC) and health outcome
| Author, Year | Study type (LOE) |
# of Subjectsa | Study Characteristics | Measure of Outcome |
Conclusion | |
|---|---|---|---|---|---|---|
| Thyroid Hormone Level | Przybyla et al., 2018 20 | Cross-sectional study (4) | 850 M, 710 F | Measurement of urinary BP-3 concentration and serum thyroid hormone levels | T3, T4, TSH levels | No significant association between BP-3 and thyroid hormone levels |
| Aker et al., 2018 19 | Case-control study (3) | 439 pregnant F | Measurement of urinary BP-3 concentration and serum thyroid hormone levels | T3, T4, T3/T4 ratio, TSH, FT4 levels | No significant association between BP-3 and thyroid hormone levels, although the author reported an inverse trend with T3 and T4 | |
| Kim et al., 2017 17 | Retrospective cohort study (3) | 1829 M/F | Measurement of urinary BP-3 concentration and serum thyroid hormone levels | T3, T4, FT3, FT4, TSH levels | High BP-3 concentration was associated with decrease FT4 and T4 | |
| Aker et al., 2016 18 | Prospective cohort study (2) | 106 pregnant F | Measurement of urinary BP-3 concentration and serum hormone levels at two time points (16-20 wks and 24-28 wks) during pregnancy | FT3, FT4, TSH levels | An IQR increase in BP-3 was significantly associated with 3% decrease in free T3; no significance with TSH or T4 | |
| Janjua et al., 2007 21 | Single-blinded clinical trial (4) | 32 M/F | Measurement of serum thyroid hormone levels before and after whole-body topical application of sunscreen + 10% of BP3, OMC and 4-MBC for QD for one week | TBG, TSH, T3, T4, FT3, FT4 levels | No biologically significant change in thyroid hormone levels, although statistical difference was observed likely due to normal hormonal variation | |
| Fertility | Buck Louis et al., 2015 25 | Case-control study (3) | 413 M | Measurement of urinary BP-3 concentration and semen analysis | Semen parameters | No significant association between BP-3 concentration and semen quality |
| Buck Louis et al., 2014 22 | Prospective cohort study (2) | 501 couples | Measurement of urinary BP-3 concentration and fecundity | The number of menstrual cycles required to achieve pregnancy | No significant association between BP-3 concentration and fecundity | |
| Chen et al., 2013 23 | Case-control study (3) | 877 idiopathic infertile male, 713 controls | Measurement of urinary BP-3 concentration and semen analysis | Semen parameters (volume, sperm concentration and number) | No significant association between BP-3 concentrations and idiopathic male infertility and semen parameters | |
| Chen et al., 2013 24 | Case-control study (3) | 70 couples with spontaneous abortions, 180 control couples | Measurement of urinary BP-3 concentration and the rate of spontaneous abortions | Rate of spontaneous abortions | No significant association between BP-3 and spontaneous abortions | |
| Reproductive hormone level | Pollack et al., 2018 26 | Prospective cohort study (2) | 143 premenopausal F | Measurement of urinary BP-3 concentration and reproductive hormones over two menstrual cycles | Reproductive hormone levels (estradiol, progesterone, FSH, LH) | Single-chemical exposure model: No significant association between BP-3 and reproductive hormones Multi-chemical exposure model: Negative association between BP-3 and FSH and LH |
| Scinicariello et al., 2016 27 | Cross-sectional study (4) | 588 M/F | Measurement of urinary BP-3 concentration and serum testosterone levels | Serum testosterone | Male adolescents in the 3rd and 4th quartiles of BP-3 had significantly lower total testosterone (−38.74%; 95% CI: −58.52, −10.42) and (−36.87%; 95% CI: −59.34, −1.98) | |
| Aker et al., 2016 18 | Prospective cohort Study (2) | 106 pregnant F | Measurement of urinary BP-3 concentration and serum hormone levels at two time points (16-20 wks and 24-28 wks) during pregnancy | estradiol, progesterone, SHBG levels | IQR inc in BP-3 was signif. associated with 10.3% dec. in SHBG at second time point but not first time point; no significance w/ estradiol or progesterone | |
| Janjua et al., 2004 14 | Single-blinded clinical trial (1) | 32 M/F | Plasma reproductive hormone levels were measured before and after whole-body topical application of sunscreen for a week | Reproductive hormone levels (testosterone, estradiol, progesterone, FSH, LH) | Decrease in plasma testosterone after the application, but likely due to normal hormonal variation. No association with other female reproductive hormones | |
| Pubertal development | Binder et al., 2018 28 | Prospective cohort study (2) | 200 F | Measurement of urinary BP-3 concentration at two time points: prior to the onset of breast development (B1) and during adolescence (B4); age of menarche was recorded | Age of menarche | A higher BP-3 concentration at B1 was associated with earlier menarche (HR: 1.17; 95% CI: 1.06, 1.29) |
| Wolff et al., 2015 29 | Prospective cohort study (2) | 1239 girls at age 6-8 years old | Measurement of urinary BP-3 concentration at enrollment. Subjects were followed annually for 7 years to determine the age at first breast or pubic hair development. | Pubertal onset | BP-3 concentration was associated with later onset of breast development 5-6 months later, (AOR: 0.80; 95% CI: 0.65, 0.98) | |
| Adiposity | Xue et al., 2015 31 | Case-control study (3) | 49 obese children 27 non-obese control | Measurement of urinary BP-3 concentration and clinical evaluation of obesity | Rate of obesity | No significant association between BP-3 concentration and the likelihood of obesity |
| Renal function | Kang et al., 2019 30 | Cross-sectional study (4) | 441 F | Measurement of urinary BP-3 concentratoin and albumin-to-creatine ratio (ACR) at a single time point | Urinary albumin-to-creatine ratio (AR) | Positive association between the concentration of BP-1, a metabolite of BP-3, and ACR |
| Child's birth weight and size | Messerlian et al., 2018 35 | Prospective cohort study (2) | 346 mother-child cohorts | Measurement of urinary BP-3 concentration from both men and women prior to conception and second measurement from women during pregnancy; birth weight and head circumferences of infants were assessed | birth weight and size | No significant association between maternal BP-3 and the birth weight |
| Ferguson et al., 2018 36 | Prospective cohort study (2) | 476 mother-child cohorts | Measurement of paternal and maternal prenatal urinary BP-3 concentration and newborn's size and weight at delivery | birth weight and size | No significant association between maternal BP-3 and the birth weight | |
| Tang et al., 2013 50 | Prospective cohort study (2) | 567 mother-child cohorts | Measurement of maternal prenatal urinary BP-3 concentration prior to delivery and newborn's weight, length and gestational age | birth weight, size and length of gestation | No significant association between BP-3 concentrations and the birth weight and size. Prenatal BP-3 concentration was associated with decreased length of gestation (−0.45 week; 95% CI: −0.87, −0.04) p-value=0.03 | |
| Philippat et al., 2012 38 | Prospective cohort study (2) | 191 mother-child cohorts | Measurement of paternal and maternal prenatal urinary BP-3 concentration and newborn's size and weight at delivery | birth weight and size | No significant association between maternal BP3 and the birth weight (26g; CI: −2, 54), but author mentioned that a positive trend exists. | |
| Wolff et al., 2008 45 | Prospective cohort study (2) | 404 mother-child cohorts | Measurement of paternal and maternal prenatal urinary BP-3 concentration and newborn's size and weight at delivery | birth weight and size | BP3 was associated with increasing birth weight in boys (44 g; 95% CI: 5.4, 84) per 1 ln-transformed biomarker, but decreasing birthweight in girls (but no statistical data shown for girls) | |
| Child's sexual maturation | Harley et al., 2019 40 | Prospective cohort study (2) | 179 mother-daughter cohorts 159 mother-son cohorts | Measurement of maternal prenatal urinary BP-3 concentration. Children were followed up for pubertal assessments | Pubertal onset in children | No significant association of prenatal urinary BP3 concentrations with pubertal onset |
| Child's birth abnormality | Huo et al., 2016 46 | Case-control study (3) | 101 Hirschsprug's disease (HSCR) patient's mother-child 322 control | Measurement of urinary BP-3 concentration from HSCR patient’s mother and control | The odds of giving birth to child with HSCR | Higher BP-3 exposure groups were more likely to give birth of HSCR children (adjusted OR = 2.39; 95% CI=1.10, 5.21). However, the urine sample was not collected during pregnancy. |
| Chevrier et al., 2012 41 | Case-control study (3) | 5200 mother-child cohorts | Urine samples were collected from mothers who gave birth to boys with hypospadias and undescended testis, and three controls per case were selected among male singleton live births | The odds of giving birth to child with hypospadias and undescended testes | No significant association between maternal BP-3 and male genital abnormalities | |
| Child's body fat mass | Buckley et al., 2016 42 | Prospective cohort study (2) | 173 mother-child cohorts | Prenatal BP-3 was measured from pregnant women's urine samples; body fat mass of child was measured from 1998 to 2002. | Percent body fat | No significant association, but prenatal BP-3 concentrations were inversely associated with percent fat mass in girls (beta=−1.51, 95% CI=−3.06, 0.01) but not in boys (beta=−0.20, 95% CI=−1.69, 1.26) |
| Child's intelligence quotient (IQ) | Nakiwala et al., 2018 43 | Prospective cohort study (2) | 452 mother-son cohorts | Urine samples were collected from pregnant women at 22-29 gestational weeks. Verbal and performance IQ of children were assessed at 5-6 years old | verbal and performance IQ | No significant association between prenatal BP-3 exposure and the boys' verbal or performance IQ (uncorrected p-value ≥ 0.09) |
| Child's behavior | Philippat et al., 2017 44 | Prospective cohort study (2) | 529 mother-son cohorts | Prenatal BP-3 was measured from mother's urine samples; child's behavior was assessed by the Strength and Difficulties Questionnaire (SDQ) completed by mothers | Child's behavior | No significant association between BP-3 and child's behavior |
| Child's sex determination | Bae et al., 2016 39 | Prospective cohort study (2) | 220 parent-child cohorts | Preconception urinary BP-3 was measured from both father and mother, and the sex of child was reported | Sex ratio of child | No significant association between BP-3 and secondary sex ratio |
| Child's immune system | Buckley et al., 2018 47 | Prospective cohort study (2) | 164 mother-child cohorts | Urine samples were collected from pregnant women in the third trimester; allergy and immune system of children was assessed by questionnaire | Risk of developing atopic dermatitis, asthma, and wheeze | Wheeze was inversely associated with low BP-3 exposure in all children. No significant association exists for other allergic conditions. |
a
All subjects are adults unless otherwise stated.
Abbreviations: LOE, Level of Evidence; M, male; F, female; y/o, year-old; T3, Total triiodothyronine; T4, Total thyroxine; TSH, Thyroid Stimulating Hormone; FT3, Free triiodothyronine; FT4, Free thyroxine; QD, once a day; 4-MBC, 4-Methylbenzylidene camphor; QD, once a day; FSH, Follicle Stimulating Hormone; LH, Leutinizing Hormone; IQR, Interquartile Range; SHBG, sex hormone-binding globulin; AOR, adjusted odds ratio