bisphénol A  ( BPA ) - Canette alimentaire. © ©Inra

A blood sample could be sufficient to reveal exposure to very low doses of bisphenol A

As early as 2003, INRA scientists demonstrated the transfer of bisphenol A from female mice to their pups during gestation. Now, working in collaboration with American colleagues, they have shown that even at very low doses, it is possible to detect the metabolic fingerprint of this endocrine disruptor.  These findings open a way towards the exploration in humans of the effects of the exposure to low doses of chemicals, based on  blood samples.

Updated on 06/14/2013
Published on 02/21/2013
Keywords: Bisphenol A

Study performed by INRA scientists in Toulouse (Unité Toxalim) in collaboration with TUFTS University (Boston, USA)
Results published on 21 February 2013 in the journal "Environmental Health Perspective"

At present, the Tolerable Daily Intake (TDI) of Bisphenol A validated by expert bodies is 50 millionths of a gram per kilo and per day (50 µg/kg/day).  But several studies in animals have demonstrated the effects of doses of this order or even much lower, when exposure occurs during development, either during the growth of the foetus (prenatal exposure via the mother) or just after birth (postnatal exposure).  As early as 2003, working in the mouse, INRA scientists had demonstrated the transfer of bisphenol A from mothers (treated at a dose of 20 µg/kg/day) foetuses during gestationt. Since then, the Institute has made a major contributing to revealing the effects of this chemical contaminant, not only on fertility and fecundity, but also on other targets (intestine, liver, etc.).

With as little as 25 billionths of a gram/kg per day, a fingerprint is detectable

Other studies have recently suggested that bisphenol A, like other food and environmental contaminants qualified as "endocrine disruptors" (substances likely to disturb the physiological mechanisms controlled by hormones) may contribute to the development of obesity, or exert an effect on development of the nervous system.
This new study was performed in gestating mice exposed to bisphenol A at doses ranging from 25 ng/kg (or 25 billionths of a gram per kilo) to 25 µg/kg (25 millionths of a gram per kilo). Only samples from the pups of these mice were examined. The INRA scientists adopted an approach which involved the global assay of a broad range of small molecules (metabolites) present in the tissues examined (blood, liver, brain), using Magnetic Resonance Imaging.  They demonstrated that it was possible to recognise the metabolic fingerprint induced by perinatal exposure, including at the lowest doses of bisphenol A employed. 

 

Bisphenol A may modulate development of the brain

"Biomarker" metabolites – or in other words, those which differ at the level of tissues such as the liver or blood – between the animals that were exposed and those that were not, appeared to confirm the disruption of energy metabolism previously suggested by other teams.  Furthermore, the differences observed in the composition of brain specimens supported the hypothesis that bisphenol A might also modulate the development of this tissue. 

This new study illustrated the usefulness of so-called "global" metabolomic approaches, and demonstrated that even very small doses were likely to modulate metabolic equilibriums when exposure to endocrine disruptors such as bisphenol A occurred during susceptible periods of life (during intra-uterine growth or just after birth).

This study has also opened the way to exploring biological markers (biomarkers) of human exposure to very low doses of toxins such as endocrine disruptors, insofar as it was possible to demonstrate significant differences in metabolic profiles using simple blood samples.  The aim now is to pursue the characterisation of early biomarkers of pathological states.  INRA is therefore focusing its efforts on this opportunity, and on gaining a clearer understanding of the effects of low doses of contaminants.

This Figure shows marked differences in the metabolic profiles of brain tissues from 21-day old mouse pups, even though only their mothers were exposed to low doses of bisphenol A during gestation: Control (no bisphenol A), 0.025 µg/kg, 0.25 µg/kg and 25 µg of bisphenol A/kg. The INRA scientists used Nuclear Magnetic Resonance Imaging to perform global assays for a broad range of small endogenous molecules (metabolites) present in the tissues examined (blood, liver, brain).. © inra
This Figure shows marked differences in the metabolic profiles of brain tissues from 21-day old mouse pups, even though only their mothers were exposed to low doses of bisphenol A during gestation: Control (no bisphenol A), 0.025 µg/kg, 0.25 µg/kg and 25 µg of bisphenol A/kg. The INRA scientists used Nuclear Magnetic Resonance Imaging to perform global assays for a broad range of small endogenous molecules (metabolites) present in the tissues examined (blood, liver, brain). © inra

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Nutrition, Chemical Food Safety and Consumer Behaviour
Associated Centre(s):
Occitanie-Toulouse

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REFERENCE

Nicolas J. Cabaton, Cécile Canlet, Perinaaz R. Wadia, Marie Tremblay-Franco, Roselyne Gautier, Jérôme Molina, Carlos Sonnenschein, Jean-Pierre Cravedi, Beverly, S. Rubin, Ana M. Soto, and Daniel Zalko Low Doses of Bisphenol-A Disrupt the Metabolome in Perinatally Exposed CD-1 Mice, Environmental Health Perspective, 21 February 2013