This study examined the association between exposure to bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS) and thyroid hormone levels in 6-year-old children. The study analyzed data from 564 children in South Korea. The results found no significant association between BPA exposure and thyroid hormones. However, increased BPF exposure was associated with increased free thyroxine (T4) levels in boys and decreased levels in girls. This suggests BPF may disrupt thyroid function differently based on sex. The study contributes to limited research on health effects of BPA alternatives like BPF and BPS in young children.

1. Yoon-Young Jang1) Youn-Hee Lim2)3) Bung-Nyun Kim4) Choong Ho Shin5) Young Ah Lee5)
Johanna Inhyang Kim4) Yun-Chul Hong1)3)6)
1)Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
2) Section of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
3)Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea
4)Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, Seoul 03080, Republic
of Korea
5)Department of Pediatrics, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
6)Environmental Health Center, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
2018년 제 70차 대한예방의학회 가을학술대회 프로그램

2. Introduction
 Bisphenol A (BPA) is used in the production of polycarbonate (PC) and epoxy-
phenolic resins.
 It is widely used in electrical, electronic, mechanical, medical, food and other
miscellaneous goods.
 Several studies have revealed the risk of bisphenol A as an endocrine disrupter.
 This has led to an increase in the use of bisphenol F(BPF) or Bisphenol S(BPS)
instead of BPA.

3. Introduction
 Studies about human health effects of BPF and BPS are very rare.
 Disruption of Thyroid Hormones may play a role in growth and development of
children.
 In this study, we assessed the association of the exposure of BPA, BPF, and BPS and
thyroid hormone in 6-year old children.

4. Methods
• Environment and Development of Children (EDC) Study is a prospective cohort study
of the growth and development of children.
• We contacted 2085 mothers chosen randomly from the 10,752 target participants,
until enrolling 645 mother-child pairs in the EDC study (response rate, 31%).
• We conducted follow-ups when the children were approximately 6 years of age,
between April 2015 and August 2017.
• The children underwent health examinations at the Seoul National University Hospital
located in Jongno-gu, Seoul, Republic of Korea.

5. Methods
• We conducted an cross-sectional analysis of 564 participants in Environment and
Development of Children (EDC) Study who were 6 years old from 2015 to 2017.
• We also conducted an analysis of 511 mother urinary Bisphenol A in order to see the
association between maternal urinary Bisphenol A and children’s Thyroid Function.
• Creatinine adjusted Bisphenol A, Bisphenol F, and Bisphenol S concentration were
measured in children’s urine at 6 years of age.
• Thyroid Function Test(Thyroid Stimulating Hormone, Total T3, Free T4,
Thyroglobulin)was conducted in children’s serum at 6 years of age.

6. Methods
• We assessed the association of log-transformed urinary BPA, BPF, BPS
concentration and log-transformed serum Thyroid Hormone concentration through
multivariate linear regression.
• Potential covariates for inclusion in the statistical models were age(months), gender,
BMI, mother’s age, mother’s educational level, parity and gestational age.
• Mother’s education level was re-categorized into 2 groups(1= High school or less,
2=University or above).
• All analyses were conducted using SAS (v9.4; Cary, NC, USA) and the R software
package (v3.2.1). Two-tailed P values <0.05 were considered statistically significant.

7. Results
Figure 1. Flow diagram depicting study population.
Participants with Environment and
Development of Children (EDC) Study who
were 6 years old in 2015-2017 (n=574)
Elegible Participants (n=564)
No maternal age and
gestational week(n=4)
No TSH, T3, Free T4(n=5)
No BPA, BPF, BPS(n=1)

8. Results
Table 1. General characteristics of the subjects.
Characteristics Overall Mean ± SD, N(%)
Mean ± SD, N(%) Mean ± SD, N(%)
p-value1)
Boys Girls
Total 564(100) 294(52.1) 270(47.9)
Age(months) 71.1±1.54 71.1±1.60 71.1±1.48 0.6186
Body mass index(kg/㎡) 15.8±1.77 15.8±1.65 15.8±1.90 0.8728
Maternal age(years) 31.4±3.55 31.6±3.59 31.2±3.51 0.2438
Maternal education
High school or less 88(15.6) 48(16.3) 40(14.8)
University or above 476(84.4) 246(83.7) 230(85.2)
Gestational week(weeks) 38.7±1.61 38.8±1.49 38.5±1.72 0.0472*
Parity
First Child 337(59.8) 177(60.2) 160(59.3)
Second or more 227(40.2) 117(39.8) 110(40.7)
Abbreviations SD: standard deviation
1) P-value was assessed using t-test.

9. Results Table 2. Distributions of serum Thyroid Hormone and Urinary Bisphenol Concentrations
N Mean(SD)
Selected percentiles
25th 50th 75th 95th Max.
logTSH (µIU/mL) Whole 564 0.82±0.48 0.51 0.83 1.10 1.61 2.86
Boys 294 0.78±0.50 0.48 0.80 1.10 1.62 2.15
Girls 270 0.86±0.44 0.57 0.85 1.12 1.60 2.86
logT3(ng/dL) Whole 563 4.99±0.13 4.91 4.99 5.07 5.19 5.39
Boys 293 4.99±0.13 4.91 4.99 5.07 5.19 5.37
Girls 270 4.99±0.12 4.91 4.98 5.08 5.18 5.39
logFT4(ng/dL) Whole 563 0.14±0.09 0.09 0.13 0.20 0.29 0.43
Boys 293 0.15±0.09 0.09 0.14 0.21 0.31 0.39
Girls 270 0.13±0.09 0.08 0.13 0.18 0.29 0.43
Creatinine-adjusted l
ogBPA (ug/g Cr)
Whole 564 0.87±0.84 0.33 0.79 1.38 2.26 4.98
Boys 294 0.86±0.91 0.27 0.75 1.35 2.50 4.98
Girls 270 0.88±0.76 0.43 0.85 1.42 2.06 2.96
Creatinine-adjusted l
ogBPF (ug/g Cr)
Whole 107 -1.77±1.02 -2.59 -2.05 -1.05 0.25 1.88
Boys 56 -1.65±0.97 -2.48 -1.86 -0.90 0.08 0.45
Girls 51 -1.91±1.06 -2.65 -2.25 -1.48 0.32 1.88
Creatinine-adjusted l
ogBPS (ug/g Cr)
Whole 203 -2.34±1.38 -3.27 -2.64 -1.82 0.41 2.92
Boys 106 -2.37±1.39 -3.38 -2.65 -1.77 0.30 2.92
Girls 92 -2.31±1.37 -3.21 -2.63 -1.92 0.47 2.50
Abbreviations TSH: Thyroid Stimulating Hormone, T3: Triiodothyronine, FreeT4: Free Thyroxine, BPA: Bisphenol A, BPF:
Bisphenol F, BPS: Bisphenol S

10. Results
The model was adjusted for age(months), gender, BMI, mother’s age, mother’s education, parity, gestational weeks. Abbreviations BPA: Bisphenol A,
BPF: Bisphenol F, BPS: Bisphenol S
Table 3. Percent change(95% CIs) in thyroid hormone concentrations in relation to 2 fold increase in urinary bisphenol concentra
tion.
% change (95%CI) p-value % change (95%CI) p-value % change (95%CI) p-value
TSH T3 FT4
BPA (ug/g Cr) 0.60 (-2.55, 3.85) 0.7125 0.77 (-0.06, 1.61) 0.0669 0.11 (-0.50, 0.72) 0.7234
BPF (ug/g Cr) -1.42 (-7.59, 5.17) 0.6647 0.40 (-1.26, 2.09) 0.6387 -0.46 (-1.57, 0.67) 0.4289
BPS (ug/g Cr) 1.52 (-1.68, 4.83) 0.3549 -0.15 (-1.01, 0.73) 0.7437 0.60 (-0.02, 1.24) 0.0583

11. Results
The model was adjusted for age(months), gender, BMI, mother’s age, mother’s education, parity, gestational weeks.
Abbreviations TSH: Thyroid Stimulating Hormone, T3: Triiodothyronine, FreeT4: Free Thyroxine, BPA: Bisphenol A, BPF: Bisphenol F, BPS: Bisphenol S
N % change (95%CI) p-value N % change (95%CI) p-value
Boys Girls
BPA
TSH 294 1.32 (-2.91, 5.73) 0.5481 270 -0.44 (-5.08, 4.42) 0.8561
T3 293 0.64 (-0.50, 1.79) 0.2724 270 1.09 (-0.10, 2.29) 0.0717
FT4 293 0.49 (-0.28, 1.27) 0.2105 270 -0.51 (-1.49, 0.48) 0.3097
BPF
TSH 56 4.87 (-4.37, 15.00) 0.3120 51 -6.48 (-14.05, 1.77) 0.1201
T3 56 1.09 (-1.43, 3.68) 0.3993 51 -0.08 (-2.01, 1.90) 0.9391
FT4 56 1.45 (0.11, 2.81) 0.0343* 51 -2.27 (-3.75, -0.78) 0.0030*
BPS
TSH 106 0.87 (-4.01, 6.00) 0.7323 97 2.53 (-1.73, 6.97) 0.2482
T3 105 -0.59 (-1.96, 0.80) 0.4043 97 0.73 (-0.34, 1.82) 0.1866
FT4 105 0.60 (-0.25, 1.45) 0.1637 97 0.76 (-0.25, 1.78) 0.1390
Table 4. Percent change(95% CIs) in thyroid hormone concentrations in relation to 2 fold increase in urinary bisphenol
concentration.

12. Results
Figure2. Percent change in TSH, T3, FreeT4 concentrations by sex of 6 years od children in maternal urinary BPA.

13. Results
Figure3. Percent change in Free T4(Thyroxine) concentrations in urinary BPA, BPF, and BPS by sex of 6 years od children.

14. Discussion
• There are no reliable study to discover thyroid hormone disruption of human by
Bisphenol A structural analogues such as BPF, BPS, and so on.
• Overall, we couldn’t find any significant association among BPA and its analogues and
Thyroid hormone.
• However, when stratified by gender, both boys and girls showed significant results
from the relationship of BPF and Free T4.
• When BPF was doubled, Free T4 was increased by 1.45% for boys and was
decreased by 2.27% for girls.

15. Discussion
• These results suggest that the Thyroid hormone alteration due to exposure of BPF in
children’s body might cause the disruption of Thyroid function as demonstrated by
animal experiments in zebrafish by Lee et al. (2016)
• While thyroid poisoning and thyroid tumor diagnosed by increase of free T4 are not a
frequent disease in children, the decrease in thyroid function caused by decrease of
free T4 might cause serious growth and development problem in children.
• This kind of disorders have profound impacts on the general health and well-being of
one’s life and their families and bring substantial financial costs(Leibson et al., 2001).

16. Discussion
• The strengths
 As far as we know, this is the first study on the exposure of BPF and BPS to
preschool aged children, the period in which children’s growth and development is
predominant.
• The limitations
 Although iodine intake is required for the production of thyroid hormone, we did
not access the associations among BPA and its analogues and thyroid hormone
according to their iodine nutritional status.

17. If you have any question, please feel free to contact me.
yuyujang88@snu.ac.kr