Endocrine-disrupting chemicals found in the urine of Danish infants

By Dr. Liji Thomas, MDReviewed by Benedette Cuffari, M.Sc.Sep 21 2022

As concerns regarding the effects of exposure to potentially toxic substances on fetal and infant health rise, researchers report the finding of several endocrine-disruptor chemicals in Danish infants in a recent Environment International journal study. More specifically, this study found that breastfeeding is associated with a higher concentration of some of these chemicals or their metabolites in infants compared to those fed a mixed diet.

Study: Benzophenones, bisphenols and other polychlorinated/phenolic substances in Danish infants and their parents - including longitudinal assessments before and after introduction to mixed diet. Image Credit: Prostock-studio / Shutterstock.com

Introduction

Bisphenols and benzophenones (BPs) are two examples of phenolic and polychlorinated substances that humans are exposed to within their environment. These chemicals are commonly used in manufacturing consumer products; thus, they are considered ubiquitous.

BPs, for example, filter out ultraviolet (UV) rays in various consumer products, including skin creams or curtains with UV screening properties. In addition, Bisphenols, including the widely studied bisphenol A (BPA), one of the most abundantly manufactured chemicals in the world, are used to manufacture epoxy resins and polycarbonates in consumer products and during recycling.

Triclosan and triclocarban are antibacterial agents used in personal care and cleaning/disinfection products. Chlorophenols can be incorporated into pesticides and herbicides, with 2,5-dichlorophenol (2,5-DCP) also used as a disinfectant.

Phenylphenols are fungicidal agents and are often used post-harvest to prevent fungal growth in fruit orchards. These chemicals may also be used for industrial or household disinfection.

Most of these chemicals undergo rapid degradation and are eliminated through urine and/or feces, thus indicating that they are not persistent. However, some chemicals exhibit pseudo-persistence, thus allowing them to remain present in the body almost all the time due to repeated or constant ingestion, skin contact, or inhalation. This continuous exposure is being investigated due to its potential for endocrine disruption.  

In Denmark, most young men continue to be exposed to most of these chemicals despite current efforts to reduce their use. BPA substitutes like bisphenol S (BPS) and bisphenol F (BPF) are being produced in more significant quantities and, as a result, have been used on a larger scale in Europe and the United States over the last ten years.

The current human biomonitoring study was conducted aimed to follow up measurements of these substances in the urine and serum of parents and infants during breastfeeding and mixed diet feeding periods.

This study, which was named TRIO, included an analysis of the urine samples of over one hundred infants and their parents. Paired samples from about 60 infants from the FOOD study during the period when they were exclusively breastfed and after exposure to a mixed diet were also included.

Study findings

Of the 22 substances measured in the urine, 12 were present in over 50% of samples from parents and infants. The concentrations of excreted substances varied significantly between samples.

In the TRIO study, BP-3 was present in almost all samples from infants and parents. In addition, BPA, BPS, triclosan, and 2,4-DCP were identified in over 75% of parental samples and, except for 2,4-DCP, almost 95% of infant samples. BP-1 was also commonly observed in all samples.

Urine samples from fathers had significantly higher urinary concentrations of these substances as compared to those obtained from mothers. However, this difference disappeared when estimated daily urinary excretion (DUE) values were used.

Infants had DUE values for BP, 4-hydroxy-benzophenone (4-BHP), BPA, BPS, triclosan, and 2-phenylphenol that were much higher than those of their parents. The highest levels of BP-3 were identified in some infant samples, with some patient samples reaching 20 and 40 times as high as the peak value among fathers and mothers, respectively.

The concentrations of triclosan, as well as BP-1 and BP-3, were highly correlated with each other, thus suggesting that all originated from the same domestic sources. The levels of these compounds in infants and their mothers were also well correlated, as were 4-BHP and BPA levels.

Between families, greater variation was observed for the levels of these compounds compared to within families, where parents showed a good correlation between themselves. Other than these substances, others showed similar increases or decreases in correlation.

Thus, simultaneous exposure to several substances may have occurred within some families. Notably, certain compounds, such as BP-1 and 4-HBP, are by-products of BP and BP-3 metabolism and compounds in use for their own properties.

In the FOOD study, seven substances, including BP, BP-1, BP-3, 4-HBP, BPA, and BPS, were present in over 50% of urine samples in both groups. The excretion profile changed with the analysis method; however, some were higher in infants compared to their parents.

After adjustment for osmolality, BP-1, BPA, BPS, and 2,4-DCP were lower; however, 4-BHP was higher in exclusively breastfed infants.

When adjusted for body weight, exclusively breastfed infants excreted 4-BHP and triclosan at higher concentrations than when they were introduced to other foods. This could be due to inhalation of chemicals from personal care products or cleaning products, even those used by their parents. Breastmilk could be another source of these substances.

In the mixed diet group, 2,4-DCP, 2-PP, and 2,5-DCP were more commonly detected. This is likely because many of these are pesticides used in growing grains, fruits, and vegetables, all of which form the base for solid foods.

The average age of infants in the exclusive breastfeeding cohort was two weeks old compared to 30 weeks in the mixed diet cohort. Thus, the exposure length should be considered when assessing the urinary excretion profile.

No correlations were found for any substance between the two groups, with intra-individual variation much higher than inter-individual differences.

Implications

Low levels of chemicals were found to be excreted in the urine of both infants and parents; however, the presence of several endocrine-disruptor chemicals in the same samples indicates the potential for additive effects with each other, as well as with other substances in the diet or the environment at large. Most of this exposure originated from household chemicals and parental or infant personal care products.

Overall, parental exposure reflected infant exposure, though the levels significantly varied between adults and infants within families. Higher mean levels have been found in pregnant women and preconceptionally in several studies conducted in France, the U.S., and Puerto Rico. This could be due to the intentional phasing out of these compounds over the last few years in Denmark.

Interestingly, triclosan detection rates were high; however, this substance is only allowed in a very small group of personal care products in Denmark and at a very low concentration.

The current study also establishes the importance of using estimated DUEs to obtain more accurate values that reflect actual exposures. This method helped demonstrate the similar or higher exposure rates of infants to several of these substances during exclusive breastfeeding as compared to the introduction of other foods.