Questions raised over exposure to bisphenol A

Chromosome abnormalities in a mouse colony have raised questions about the safe level of exposure to bisphenol A, a chemical used to make some common plastics and resins.

A sudden increase in chromosome abnormalities in a mouse colony has raised questions about the safe level of exposure for bisphenol A, a chemical used to make some common plastics and resins.

In a research paper supported by the US National Institute of Environmental Health Sciences, scientists at a genetics laboratory and an associated animal research centre, both at Case Western Reserve University in Cleveland, Ohio describe the accident in the April 1 issue of the journal Current Biology.

The scientists found that the colony’s semi-rigid plastic cages had deteriorated as the result of a handler’s use of the wrong cleaner – a harsh detergent – which damaged the cages and led to the release of small amounts of the plasticizer bisphenol A (BPA).

This low-level exposure is said to have led to ‘highly significant’ increases in abnormalities in the mice’s developing eggs (oocytes). These results were then confirmed in an experiment in which the animals’ eggs were deliberately exposed, the scientists reported.

First author Patricia A. Hunt, Ph.D., of the Department of Genetics at Case Western Reserve said that the sudden increase in abnormalities appeared in a mouse colony used as a control group.

‘We suspected it might be caused by something environmental and so for several weeks we looked for an explanation – especially for any recent changes in the lab. Nothing turned up. But as I was heading out the door for some time off, I noticed that the plastic cages looked kind of the worst for wear. I thought maybe the autoclave was causing the deterioration. I was told that the autoclave didn’t produce that effect on the plastic but that a temporary animal worker had mistakenly used a harsh, alkaline detergent on them.

‘We then confirmed that such a detergent could break down the plastic caging and water bottles chemically, exposing the mice to bisphenol A at low levels.’

The researchers then deliberately exposed mice to small amounts of bisphenol A. They found that their eggs showed greatly increased rates of two chromosome abnormalities. In normal mouse or human eggs, the chromosomes line up, ready for the egg to split in two when fertilised. But in many of the eggs of the exposed mice, the chromosomes were not aligned but disorganised. In addition, the egg cells of the exposed mice frequently had too few or too many chromosomes, a condition called aneuploidy.

These kinds of chromosomal abnormalities are the leading cause of miscarriage, congenital defects and mental retardation in humans.

Dr. Hunt said, ‘We don’t know what the effects, if any, may be on humans at these low levels, but a study in Germany indicates pregnant women are exposed to similar levels of BPA, which is used in food and beverage containers. Certainly we should be concerned enough to carry out extensive further study.’

Research on bisphenol A is said to have stirred controversy for a number of years. Generally, traditional testing has not raised concerns, but several other studies have.

In 1997, research at the University of Missouri-Columbia suggested BPA has an estrogen-like activity. In these experiments, pregnant mice were exposed to low levels of bisphenol A at a time when their male foetuses’ prostates were developing. The male offspring subsequently developed enlarged prostates at adulthood, the scientists reported in the NIEHS journal Environmental Health Perspectives.

Recently, the European Commission’s Scientific Committee on Food lowered its Tolerable Daily Intake for bisphenol A five-fold.

Several years ago, the US Environmental Protection Agency (EPA) asked the National Toxicology Program to assemble a panel of academic, government and industry scientists to make recommendations on BPA and other environmental estrogens. In 2001, the panel said, among other things, that BPA might require special types of additional testing to assure that the levels permitted are safe.

Dr. Hunt and her colleagues suggested today that their study of immature mouse eggs might be the basis for such sensitive new testing.