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Common BPA alternative, BPS, crosses into placenta

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Canadian and Chinese scientists have found the “first evidence” that bisphenol S (BPS), widely used as an alternative to BPA, can cross the human placenta.

BPS has already been detected in over 80% of urine samples from the US, China and six other Asian countries.

In 2016, Laura Vandenberg and Mary Catanese, from the University of Massachusetts Amherst, reported behavioural differences between the nesting rodent mothers, exposed to BPS during pregnancy and lactation, and their daughters exposed in utero.

In the latest study, researchers from the University of Alberta, Canada, Beijing's Ministry of Health and China National Center for Food Safety Risk Assessment analysed 61 pairs of maternal and cord blood samples, collected from pregnant women and their newborns, in Beijing and Shijiazhuang.

They measured levels of BPS and BPA metabolites: BPA-glucuronide and BPA-sulfate. Although total BPS was only detected in four maternal and seven cord blood samples, the study provides “the first evidence that BPS crosses the human placenta”, suggest the researchers.

Total BPA metabolites in cord samples were also “significantly higher” than in maternal blood.

“The foetus has more difficulty excreting BPA than the mother,” explains lead author Jonathan Martin from the University of Alberta. “The mother can easily pass metabolites through urine, whereas the foetus excretes to the amniotic fluid and, to some extent, back to the mother's circulation.”

The results are backed up by other studies pointing to higher levels of BPA metabolites on the foetal side of the placenta, suggesting that the they might be "trapped", said Laura Vandenberg, who was not involved in the Canadian study.

Levels of total BPA and BPS were not particularly high. “The interesting thing is that the metabolite profile was quite unique, with high concentrations of BPA-sulfate relative to BPA-glucuronide,” said Professor Martin.

Proportions of BPA-sulfate are higher than might be expected from oral exposure studies on non-pregnant women, he added.

“The human foetus is known to have a different metabolic capacity. It's known to have a very immature glucuronidation pathway, whereas sulfation begins earlier. So it's not uncommon for the human foetus to produce more of the sulfate than the respective glucuronide,” said Professor Martin.

“But to see the actual changes reflected in the maternal serum was quite surprising.” He suggested the metabolite profile in the mother's blood may be affected by what's occurring in the placenta or foetus.

Human biomonitoring studies often rely on detecting total BPA in urine. Biomonitoring of its metabolites is limited, while even less is known about BPA alternatives, say the researchers.

Future epidemiology studies should measure individual concentrations of free BPA and BPA-metabolites - “all of which have different toxicological profiles”, they add. 

“While some scientists have challenged measurements of BPA in human blood because of concerns over contamination during sample collection, finding the metabolites can only occur when exposures have occurred in living beings,” said Ms Vandenberg.

“This makes careful analyses of circulating metabolite concentrations super important."

“While data consistently suggest that BPA metabolites are not oestrogen mimics, that doesn't mean they are biologically inactive,” she added.

A small number of studies have shown that BPA-glucuronide may have different kinds of biological activity, at least in cultured cells, she said. “To me, this suggests that perhaps the metabolites themselves deserve a closer look.”

Echa is keeping the European Commission abreast of the latest research into the health effects of BPS so it can decide if any legal restrictions on its use in products are necessary.

Last year, after the substance was evaluated under REACH by the Belgian competent authority, the registrants were asked by the agency's Member State Committee to conduct an extended one-generation reproductive toxicity study and include the findings in the registration dossier by September 2018.

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