Biomonitoring of human exposures to chlorinated derivatives and structural analogs of bisphenol A

BPS, BPF, BPB and chlorinated derivatives likely to have similar effects than BPA

Bisphenol A (BPA) is a chemical that is widespread in the environment. Researchers reviewed and critically discussed the sources and routes of human exposure to chlorinated derivatives (ClxBPA) and alternatives to BPA (BPF, BPS), as well as their metabolism, toxicity and concentrations in human tissues. The researchers suggest BPA alternatives and derivatives may have similar effects, and provide directions for future research.


Biomonitoring of human exposures to chlorinated derivatives and structural analogs of bisphenol A, ScienceDirect, Environmental Pollution, Volume 85, December 2015, Pages 352–379.

The high reactivity of bisphenol A (BPA) with disinfectant chlorine is evident in the instantaneous formation of chlorinated BPA derivatives (ClxBPA) in various environmental media that show increased estrogen-activity when compared with that of BPA.

The documented health risks associated with BPA exposures have led to the gradual market entry of BPA structural analogs, such as bisphenol S (BPS), bisphenol F (BPF), bisphenol B (BPB), etc. A suite of exposure sources to ClxBPA and BPA analogs in the domestic environment is anticipated to drive the nature and range of halogenated BPA derivatives that can form when residual BPA comes in contact with disinfectant in tap water and/or consumer products.

The primary objective of this review was to survey all available studies reporting biomonitoring protocols of ClxBPA and structural BPA analogs (BPS, BPF, BPB, etc.) in human matrices. Focus was paid on describing the analytical methodologies practiced for the analysis of ClxBPA and BPA analogs using hyphenated chromatography and mass spectrometry techniques, because current methodologies for human matrices are complex. During the last decade, an increasing number of ecotoxicological, cell-culture and animal-based and human studies dealing with ClxBPA exposure sources and routes of exposure, metabolism and toxicity have been published. Up to date findings indicated the association of ClxBPA with metabolic conditions, such as obesity, lipid accumulation, and type 2 diabetes mellitus, particularly in in-vitro and in-vivo studies. We critically discuss the limitations, research needs and future opportunities linked with the inclusion of ClxBPA and BPA analogs into exposure assessment protocols of relevant epidemiological studies.

Exposure to Bisphenol-A derivatives: BPA alternatives likely to have similar effects

Newer analogues may also have endocrine-disrupting effects

Bisphenol A (BPA) is present in many modern consumer products. It is found in common household equipment, food and drink cans, bottles and storage containers, CDs and vehicles, and has been found at high levels in cash-register receipts. Some scientific reports have linked exposure to BPA to endocrine (hormone) disruption, and lowered testosterone levels. In February this year, France proposed BPA as a REACH regulation candidate substance of very high concern.

Exposure to BPA derivatives: newer analogues may also have endocrine-disrupting effects, Science for Environment Policy News Alert, 08 April 2016.

As a result of these concerns, alternative substances have been introduced, with a similar but not identical structure to BPA. These analogues include bisphenol S and F (BPS, BPF), which have entered the consumer product market to provide the same functionality of BPA in a safer way. However, these compounds may still pose a risk to human health.

Biomonitoring of human exposures to chlorinated derivatives and structural analogs of bisphenol A, ScienceDirect, Environmental Pollution, Volume 85, December 2015, Pages 352–379.

When BPA comes into contact with chlorine in tap water, it forms chlorinated derivatives (ClxBPA), which humans may be exposed to through water use. Findings on the health effects of ClxBPA have been based on in vitro and in vivo experiments and suggest a 10–40 times higher estrogenic activity than BPA. The health risks of BPA analogues have also been studied in the lab, which have shown links to endocrine disturbance.

Measurement of chemicals in biological substances, such as urine or blood, is called biomonitoring, and is an important method of assessing human exposure to toxic compounds.

This study, which received support from European Structural Funds, explored the findings of biomonitoring studies on ClxBPA and BPA analogues. The researchers carried out an extensive literature search to identify studies reporting biomonitoring of ClxBPA and BPA structural analogues in human samples. This led to the selection of 23 relevant articles.

The first reported human biomonitoring of ClxBPA was in 2005, while for BPA alternatives it was in 2010. Since then, 21 peer-reviewed studies have been published reporting internal exposure measurements of ClxBPA and BPA alternatives in various human samples. Articles reporting ClxBPA in human samples include fatty tissue, placenta, breast milk, urine, plasma and serum, while those reporting BPA alternatives included only urine and breast milk. The authors could not identify any studies looking at BPA analogues in other biological samples, reflecting their newer status.

Overall, the evidence suggests that human exposure to ClxBPA and BPA alternatives is widespread. The compounds have been detected in a range of environmental media and consumer products. Although the sources and pathways of exposure remain unclear, evidence suggests that BPA and its chlorinated derivatives enter the body through the airways, skin contact and ingestion.

In vitro and in vivo studies suggest BPA alternatives and chlorinated derivatives may contribute to the development of diabetes and obesity. The authors say there is a need for studies that follow lots of people over time to better understand the human health effects. They discuss methodological advances in biomonitoring protocols, and explain the need for time- and cost-effective sample-preparation procedures, faster chromatography run times and smaller sample volumes. They also discuss the need to monitor other halogenated forms of BPA (in addition to ClxBPA), which have shown adverse health effects in some studies.

Studies on humans could help to close knowledge gaps, such as the pathways that lead to exposure, sources in the environment and the potential endocrine-disrupting properties of the aforementioned BPA compounds. The authors also recommend investigations into whether other phenols in the environment contribute to metabolic disorders.