J Korean Soc Matern Child Health.  2023 Oct;27(4):205-214. 10.21896/jksmch.2023.27.4.205.

Association between Exposure to Endocrine Disrupting Chemicals in Breast Milk and Maternal Lifestyle Factor

• Kim JH
• Heo SJ
• Moon N
• Kwak JM
• Lee SM

• KMID: 2547471
• DOI: http://doi.org/10.21896/jksmch.2023.27.4.205

Abstract

This study aimed to investigate the concentrations of nonpersistent endocrine-disrupting chemicals (EDCs) and per- and polyfluoroalkyl substances (PFAS) in human milk through a literature review and to affirm the association between EDCs and lifestyle factors based on the reviewed literature. We analyzed studies reporting EDC concentrations in breast milk from literature published on Google Scholar and PubMed between 2000 and 2022. In Korea, most EDC concentrations in breast milk were comparable to or lower than those in other countries. However, the concentrations of PFAS in breast milk, especially perfluorooctanoic acid, have shown an increasing trend compared to the past in Korea. Considering the potential risks of EDCs, breastfeeding mothers should take measures to minimize their exposure to these chemicals.

Keyword

Breast milk, Endocrine disrupting chemicals, Phthalate, Bisphenol, Per- and polyfluoroalkyl substances

Figure

• 

  Fig. 1. Phthalates concentration in breast milk. This bar graph illustrates the median concentration values (μg/L) of phthalate metabolites in breast milk. NA, not available; MEP, monoethyl phthalate; MnBP, mono-n-butyl phthalate; MiBP, mono-isobutyl phthalate; MBzP, mono-benzyl phthalate; MiNP, mono-isononyl phthalate; MEHP, mono-2-ethylhexyl phthalate.

• 

  Fig. 2. Bisphenol A (BPA) concentration in breast milk. The bar graph illustrates the median value(μg/L) of BPA in breast milk.

• 

  Fig. 3. Concentrations and time trend of per- and polyfluoroalkyl substances (PFAS) in breast milk. This graph illustrates the concentration and changes in the mean levels of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in the breast milk of Korean mothers from 2007 to 2018 (pg/mL). PFOS, perfluorooctane sulfonic acid; PFOA, perfluorooctanoic acid. Adapted from Kim et al. Chemosphere 2023b;310:136688.

Reference

Abdallah MA., Wemken N., Drage DS., Tlustos C., Cellarius C., Cleere K, et al. Concentrations of perfluoroalkyl substances in human milk from Ireland: Implications for adult and nursing infant exposure. Chemosphere. 2020. 246:125724.

Arbuckle TE., Fisher M., MacPherson S., Lang C., Provencher G., LeBlanc A, et al. Maternal and early life exposure to phthalates: The Plastics and Personal-care Products use in Pregnancy (P4) study. Sci Total Environ. 2016. 551-2:344–56.

Averina M., Brox J., Huber S., Furberg AS. Exposure to perfluoroalkyl substances (PFAS) and dyslipidemia, hypertension and obesity in adolescents. The Fit Futures study. Environ Res. 2021. 195:110740.

Awad R., Zhou Y., Nyberg E., Namazkar S., Yongning W., Xiao Q, et al. Emerging per- and polyfluoroalkyl substances (PFAS) in human milk from Sweden and China. Environ Sci Process Impacts. 2020. 22:2023–30.

Bach CC., Bech BH., Brix N., Nohr EA., Bonde JP., Henriksen TB. Perfluoroalkyl and polyfluoroalkyl substances and human fetal growth: a systematic review. Crit Rev Toxicol. 2015. 45:53–67.

Bai PY., Wittert GA., Taylor AW., Martin SA., Milne RW., Shi Z. The association of socio-demographic status, lifestyle factors and dietary patterns with total urinary phthalates in Australian men. PLoS One. 2015. 10:e0122140.

Beser MI., Pardo O., Beltrán J., Yusà V. Determination of 21 perfluoroalkyl substances and organophosphorus compounds in breast milk by liquid chromatography coupled to orbitrap high-resolution mass spectrometry. Anal Chim Acta. 2019. 1049:123–32.

Cao XL., Popovic S., Arbuckle TE., Fraser WD. Determination of free and total bisphenol A in human milk samples from Canadian women using a sensitive and selective GC-MS method. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2015. 32:120–5.

Carrizosa C., Murcia M., Ballesteros V., Costa O., Manzano-Salgado CB., Ibarluzea J, et al. Prenatal perfluoroalkyl substance exposure and neuropsychological development throughout childhood: The INMA Project. J Hazard Mater. 2021. 416:125185.

Černá M., Grafnetterová AP., Dvořáková D., Pulkrabová J., Malý M., Janoš T, et al. Biomonitoring of PFOA, PFOS and PFNA in human milk from Czech Republic, time trends and estimation of infant's daily intake. Environ Res. 2020. 188:109763.

Chang CH., Huang YF., Wang PW., Lai CH., Huang LW., Chen HC, et al. Associations between prenatal exposure to bisphenol a and neonatal outcomes in a Taiwanese cohort study: mediated through oxidative stress? Chemosphere. 2019. 226:290–7.

Chen F., Yin S., Kelly BC., Liu W. Chlorinated polyfluoroalkyl ether sul fonic acids in matched maternal, cord, and placenta samples: a study of transplacental transfer. Environ Sci Technol. 2017a. 51:6387–94.

Chen F., Yin S., Kelly BC., Liu W. Isomer-specific transplacental transfer of perfluoroalkyl acids: results from a survey of paired maternal, cord sera, and placentas. Environ Sci Technol. 2017b. 51:5756–63.

Christensen KY., Thompson BA., Werner M., Malecki K., Imm P., An-derson HA. Levels of persistent contaminants in relation to fish consumption among older male anglers in Wisconsin. Int J Hyg Environ Health. 2016. 219:184–94.

Deceuninck Y., Bichon E., Marchand P., Boquien CY., Legrand A., Boscher C, et al. Determination of bisphenol A and related substitutes/analogues in human breast milk using gas chromatographytandem mass spectrometry. Anal Bioanal Chem. 2015. 407:2485–97.

Deng M., Liang X., Du B., Luo D., Chen H., Zhu C, et al. Beyond classic phthalates: occurrence of multiple emerging phthalate alternatives and their metabolites in human milk and implications for combined exposure in infants. Environ Sci Technol Lett. 2021. 8:705–12. https://doi.org/10.1021/acs.estlett.1c00476.

Denys S., Fraize-Frontier S., Moussa O., Le Bizec B., Veyrand B., Volatier JL. Is the fresh water fish consumption a significant deter-minant of the internal exposure to perfluoroalkylated substances (PFAS)? Toxicol Lett. 2014. 231:233–8.

Di Napoli I., Tagliaferri S., Sommella E., Salviati E., Porri D., Raspini B, et al. Lifestyle habits and exposure to BPA and phthalates in women of childbearing age from Northern Italy: a pilot study. Int J Environ Res Public Health. 2021. 18:9710.

Dualde P., Pardo O., Corpas-Burgos F., Kuligowski J., Gormaz M., Vento M, et al. Biomonitoring of bisphenols A, F, S in human milk and probabilistic risk assessment for breastfed infants. Sci Total Environ. 2019. 668:797–805.

EFSA Panel on Contaminants in the Food Chain (EFSA CONTAM Panel)., Knutsen HK., Alexander J., Barregård L., Bignami M., Brüschweiler B, et al. Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food. EFSA J. 2018. 16:e05194.

EFSA Panel on Contaminants in the Food Chain (EFSA CONTAM Panel)., Schrenk D., Bignami M., Bodin L., Chipman JK., Del Mazo J, et al. Risk to human health related to the presence of perfluoroalkyl substances in food. EFSA J. 2020. 18:e06223.

Fair PA., Wolf B., White ND., Arnott SA., Kannan K., Karthikraj R, et al. Perfluoroalkyl substances (PFASs) in edible fish species from Charleston Harbor and tributaries, South Carolina, United States: exposure and risk assessment. Environ Res. 2019. 171:266–77.

Fernandes AR., Mortimer D., Holmes M., Rose M., Zhihua L., Huang X, et al. Occurrence and spatial distribution of chemical contaminants in edible fish species collected from UK and proximate marine waters. Environ Int. 2018. 114:219–30.

Fisher M., MacPherson S., Braun JM., Hauser R., Walker M., Feeley M, et al. Paraben concentrations in maternal urine and breast milk and its association with personal care product use. Environ Sci Technol. 2017. 51:4009–17.

Fromme H., Gruber L., Seckin E., Raab U., Zimmermann S., Kiranoglu M, et al. Phthalates and their metabolites in breast milk-results from the Bavarian Monitoring of Breast Milk (BAMBI). Environ Int. 2011. 37:715–22.

Genuis SJ., Beesoon S., Lobo RA., Birkholz D. Human elimination of phthalate compounds: blood, urine, and sweat (BUS) study. ScientificWorldJournal. 2012. 2012:615068.

Guerranti C., Sbordoni I., Fanello EL., Borghini F., Corsi I., Focardi SE. Levels of phthalates in human milk samples from central Italy. Microchem J. 2013. 107:178–81. https://doi.org/10.1016/j.microc.2012.06.014.

Hallberg I., Björvang RD., Hadziosmanovic N., Koekkoekk J., Pikki A., van Duursen M, et al. Associations between lifestyle factors and levels of per- and polyfluoroalkyl substances (PFASs), phthalates and parabens in follicular fluid in women undergoing fertility treatment. J Expo Sci Environ Epidemiol. 2023. 33:699–709.

Harris MH., Oken E., Rifas-Shiman SL., Calafat AM., Bellinger DC., Webster TF, et al. Prenatal and childhood exposure to per- and polyfluoroalkyl substances (PFAS) and child executive function and behavioral problems. Environ Res. 2021. 202:111621.

Hartle JC., Cohen RS., Sakamoto P., Barr DB., Carmichael SL. Chemical contaminants in raw and pasteurized human milk. J Hum Lact. 2018. 34:340–9.

Haug LS., Thomsen C., Brantsaeter AL., Kvalem HE., Haugen M., Becher G, et al. Diet and particularly seafood are major sources of perfluorinated compounds in humans. Environ Int. 2010. 36:772–8.

Henderson NB., Sears CG., Calafat A., Chen A., Lanphear B., Romano M, et al. Associations of breast milk consumption with urinary phtha late and phenol exposure biomarkers in infants. Environ Sci Technol Lett. 2020. 7:733–9. https://doi.org/10.1021/acs.estlett.0c00450.

Hines EP., Mendola P., von Ehrenstein OS., Ye X., Calafat AM., Fenton SE. Concentrations of environmental phenols and parabens in milk, urine and serum of lactating North Carolina women. Reprod Toxicol. 2015. 54:120–8.

Högberg J., Hanberg A., Berglund M., Skerfving S., Remberger M., Calafat AM, et al. Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations. Environ Health Perspect. 2008. 116:334–9.

Hung SC., Lin TI., Suen JL., Liu HK., Wu PL., Wu CY, et al. Phthalate exposure pattern in breast milk within a six-month postpartum time in Southern Taiwan. Int J Environ Res Public Health. 2021. 18:5726.

Jain RB. Contribution of diet and other factors to the levels of selected polyfluorinated compounds: data from NHANES 2003-2008. Int J Hyg Environ Health. 2014. 217:52–61.

Jin H., Mao L., Xie J., Zhao M., Bai X., Wen J, et al. Poly- and perfluoroalkyl substance concentrations in human breast milk and their associations with postnatal infant growth. Sci Total Environ. 2020a. 713:136417.

Jin H., Xie J., Mao L., Zhao M., Bai X., Wen J, et al. Bisphenol analogue concentrations in human breast milk and their associations with postnatal infant growth. Environ Pollut. 2020b. 259:113779.

Kahn LG., Philippat C., Nakayama SF., Slama R., Trasande L. Endocrine-disrupting chemicals: implications for human health. Lancet Dia-betes Endocrinol. 2020. 8:703–18.

Kang H., Choi K., Lee HS., Kim DH., Park NY., Kim S, et al. Elevated levels of short carbon-chain PFCAs in breast milk among Korean women: Current status and potential challenges. Environ Res. 2016. 148:351–9.

Kim JH., Kim D., Moon SM., Yang EJ. Associations of lifestyle factors with phthalate metabolites, bisphenol A, parabens, and triclosan concentrations in breast milk of Korean mothers. Chemosphere. 2020a. 249:126149.

Kim JH., Moon N., Ji E., Moon HB. Effects of postnatal exposure to phthalate, bisphenol a, triclosan, parabens, and per- and poly-fluoroalkyl substances on maternal postpartum depression and infant neurodevelopment: a Korean mother-infant pair cohort study. Environ Sci Pollut Res Int. 2023a. 30:96384–99.

Kim JH., Moon N., Lee JW., Mehdi Q., Yun MH., Moon HB. Time-course trend and influencing factors for per- and polyfluoroalkyl substances in the breast milk of Korean mothers. Chemosphere. 2023b. 310:136688.

Kim JH., Shin HS., Lee WH. Impact of endocrine-disrupting chemicals in breast milk on postpartum depression in Korean mothers. Int J Environ Res Public Health. 2021. 18:4444.

Kim S., Eom S., Kim HJ., Lee JJ., Choi G., Choi S, et al. Association between maternal exposure to major phthalates, heavy metals, and persistent organic pollutants, and the neurodevelopmental performances of their children at 1 to 2years of age- CHECK cohort study. Sci Total Environ. 2018. 624:377–84.

Kim S., Lee I., Lim JE., Lee A., Moon HB., Park J, et al. Dietary contribution to body burden of bisphenol A and bisphenol S among mother-children pairs. Sci Total Environ. 2020b. 744:140856.

Kim S., Lee J., Park J., Kim HJ., Cho G., Kim GH, et al. Concentrations of phthalate metabolites in breast milk in Korea: estimating exposure to phthalates and potential risks among breastfed infants. Sci Total Environ. 2015. 508:13–9.

Kim SK., Lee KT., Kang CS., Tao L., Kannan K., Kim KR, et al. Distribution of perfluorochemicals between sera and milk from the same mothers and implications for prenatal and postnatal exposures. Environ Pollut. 2011. 159:169–74.

Larsson K., Ljung Björklund K., Palm B., Wennberg M., Kaj L., Lindh CH, et al. Exposure determinants of phthalates, parabens, bisphenol A and triclosan in Swedish mothers and their children. Environ Int. 2014. 73:323–33.

Latini G., Wittassek M., Del Vecchio A., Presta G., De Felice C., Angerer J. Lactational exposure to phthalates in Southern Italy. Environ Int. 2009. 35:236–9.

Lee J., Choi K., Park J., Moon HB., Choi G., Lee JJ, et al. Bisphenol A distribution in serum, urine, placenta, breast milk, and umbilical cord serum in a birth panel of mother-neonate pairs. Sci Total Environ. 2018a. 626:1494–501.

Lee S., Kim S., Park J., Kim HJ., Choi G., Choi S, et al. Perfluoroalkyl substances (PFASs) in breast milk from Korea: time-course trends, influencing factors, and infant exposure. Sci Total Environ. 2018b. 612:286–92.

Lin S., Ku HY., Su PH., Chen JW., Huang PC., Angerer J, et al. Phthalate exposure in pregnant women and their children in central Taiwan. Chemosphere. 2011. 82:947–55.

Liu M., Nordstrom M., Forand S., Lewis-Michl E., Wattigney WA., Kannan K, et al. Assessing exposures to per- and polyfluoroalkyl substances in two populations of Great Lakes Basin fish con-sumers in Western New York State. Int J Hyg Environ Health. 2022. 240:113902.

Macheka LR., Abafe OA., Mugivhisa LL., Olowoyo JO. Occurrence and infant exposure assessment of per and polyfluoroalkyl substances in breast milk from South Africa. Chemosphere. 2022. 288(Pt 2):132601.

Main KM., Mortensen GK., Kaleva MM., Boisen KA., Damgaard IN., Chellakooty M, et al. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environ Health Perspect. 2006. 114:270–6.

Martin L., Zhang Y., First O., Mustieles V., Dodson R., Rosa G, et al. Lifestyle interventions to reduce endocrine-disrupting phthalate and phenol exposures among reproductive age men and women: A review and future steps. Environ Int. 2022. 170:107576.

Mendonca K., Hauser R., Calafat AM., Arbuckle TE., Duty SM. Bisphenol A concentrations in maternal breast milk and infant urine. Int Arch Occup Environ Health. 2014. 87:13–20.

Migeot V., Dupuis A., Cariot A., Albouy-Llaty M., Pierre F., Rabouan S. Bisphenol a and its chlorinated derivatives in human colostrum. Environ Sci Technol. 2013. 47:13791–7.

Mora AM., Fleisch AF., Rifas-Shiman SL., Woo Baidal JA., Pardo L., Webster TF, et al. Early life exposure to per- and polyfluoroalkyl substances and mid-childhood lipid and alanine aminotransferase levels. Environ Int. 2018. 111:1–13.

Mortensen GK., Main KM., Andersson AM., Leffers H., Skakkebaek NE. Determination of phthalate monoesters in human milk, consumer milk, and infant formula by tandem mass spectrometry (LC-MS-MS). Anal Bioanal Chem. 2005. 382:1084–92.

Niu Y., Wang B., Zhao Y., Zhang J., Shao B. Highly sensitive and high-throughput method for the analysis of bisphenol analogues and their halogenated derivatives in breast milk. J Agric Food Chem. 2017. 65:10452–63.

Rovira J., Martínez MÁ., Mari M., Cunha SC., Fernandes JO., Marmelo I, et al. Mixture of environmental pollutants in breast milk from a Spanish cohort of nursing mothers. Environ Int. 2022. 166:107375.

Sadia M., Yeung LWY., Fiedler H. Trace level analyses of selected perfluoroalkyl acids in food: method development and data gene-ration. Environ Pollut. 2020. 263(Pt A):113721.

Serrano SE., Braun J., Trasande L., Dills R., Sathyanarayana S. Phthalates and diet: a review of the food monitoring and epidemiology data. Environ Health. 2014. 13:43.

Snoj Tratnik J., Kosjek T., Heath E., Mazej D., Ćehić S., Karakitsios SP, et al. Urinary bisphenol A in children, mothers and fathers from Slovenia: overall results and determinants of exposure. Environ Res. 2019. 168:32–40.

Steenland K., Barry V., Savitz D. Serum perfluorooctanoic acid and birthweight: an updated meta-analysis with bias analysis. Epide-miology. 2018. 29:765–76.

Stone J., Sutrave P., Gascoigne E., Givens MB., Fry RC., Manuck TA. Exposure to toxic metals and per- and polyfluoroalkyl substances and the risk of preeclampsia and preterm birth in the United States: a review. Am J Obstet Gynecol MFM. 2021. 3:100308.

Sun Y., Irie M., Kishikawa N., Wada M., Kuroda N., Nakashima K. Determination of bisphenol A in human breast milk by HPLC with column-switching and fluorescence detection. Biomed Chromatogr. 2004. 18:501–7.

Tao L., Kannan K., Wong CM., Arcaro KF., Butenhoff JL. Perfluorinated compounds in human milk from Massachusetts, U.S.A. Environ Sci Technol. 2008. 42:3096–101.

Tuzimski T., Pieniążek D., Buszewicz G., Teresiński G. QuEChERS-based extraction procedures for the analysis of bisphenols S and A in breast milk samples by LC-QqQ-MS. J AOAC Int. 2018 Oct 17. https://doi.org/10.5740/jaoacint.18-0297 [Epub].

Tuzimski T., Szubartowski S. Method development for selected bisphenols analysis in sweetened condensed milk from a can and breast milk samples by HPLC-DAD and HPLC-QqQ-MS: com-parison of sorbents (Z-SEP, Z-SEP Plus, PSA, C18, Chitin and EMR-Lipid) for clean-up of QuEChERS extract. Molecules. 2019. 24:2093.

Wenzel AG., Brock JW., Cruze L., Newman RB., Unal ER., Wolf BJ, et al. Prevalence and predictors of phthalate exposure in pregnant women in Charleston, SC. Chemosphere. 2018. 193:394–402.

Zeng XW., Qian Z., Emo B., Vaughn M., Bao J., Qin XD, et al. Association of polyfluoroalkyl chemical exposure with serum lipids in children. Sci Total Environ. 2015. 512-3:364–70.

Zheng G., Schreder E., Dempsey JC., Uding N., Chu V., Andres G, et al. Per- and polyfluoroalkyl substances (PFAS) in breast milk: con-cerning trends for current-use PFAS. Environ Sci Technol. 2021. 55:7510–20.

Zimmers SM., Browne EP., O'Keefe PW., Anderton DL., Kramer L., Reckhow DA, et al. Determination of free bisphenol A (BPA) concentrations in breast milk of U.S. women using a sensitive LC/MS/MS method. Chemosphere. 2014. 104:237–43.