In an article published on February 12, 2022, in the International Journal of Hygiene and Environmental Health, Andreas Kortenkamp and co-authors from Brunel University London, UK, systematically reviewed animal and epidemiological studies to investigate the association between bisphenol A (BPA) exposure and declining semen quality. Several studies have reported an association between exposure to endocrine-disrupting chemicals, including BPA, and declines in several parameters of semen quality (FPF reported and here), however a “widely held view [is] that there is ‘conflicting’ evidence” for it, which the authors stated as the rationale for their work.
Kortenkamp and co-authors searched PubMed, Web of Science, and Scopus for literature meeting their eligibility criteria published until August 2021. They identified 26 experimental studies with rats and mice as well as 16 epidemiological studies of which they evaluated the strength of evidence for BPA exposure to be associated with declines in semen quality. The analysis showed that “the overall strength of evidence that associates BPA with poor semen quality in experimental studies can be evaluated as ‘robust.’” Many studies reporting negative findings were found to lack sensitivity, and sufficient controls of background contamination, as well as may be related to potential hormonal interference. For the epidemiological studies, the scientists also observed a “robust” association, but the studies reporting a positive association were rated as “medium” or “medium to high” confidence while corresponding animal studies were rated of “high” confidence. The authors emphasized that their findings “support the conclusion that the patterns seen in animal experiments are relevant to humans.”
Based on the animal studies, Kortenkamp and co-authors further estimated the reference dose for declines in semen quality of BPA for use in mixture risk assessments. The no-observed adverse effect levels (NOAELs) derived in the high confidence studies varied such that reference doses could be between 0.0001 and 0.0099 µg/kg body weight/day. Balancing “between caution suggested by studies at the lower end of the doses and the weight of evidence from studies with higher NOAELs,” the scientists determined a reference dose of 0.003 µg/kg/d, which is below the current exposure of the European population to BPA. Furthermore, at this level also some of the epidemiological studies analyzing BPA exposure of adults observed effects.
The authors highlighted that their approach varies from standards to derive a tolerable daily intake (TDI) for exposure since they did not intend to calculate a value for single chemical exposure but rather to use in mixture risk assessments.
While the researchers’ evaluation was underway, the European Food Safety Authority (EFSA) proposed a new TDI of 0.00004 µg/kg body weight/day which is 100,000-times lower than the previous value of 4 μg/kg body weight/day (FPF reported and here) and lower than the value derived by Kortenkamp et al. However, the researcher also applied another approach to calculate the reference dose.
Reference
Kortenkamp, A. et al (2022). “Bisphenol A and declining semen quality: A systematic review to support the derivation of a reference dose for mixture risk assessments.” International Journal of Hygiene and Environmental Health. DOI: 10.1016/j.ijheh.2022.113942
