Koehler, KE, RC Voigt, S Thomas, B Lamb, C Urban, T Hassold and PA Hunt. 2003. When Disaster Strikes: Rethinking Caging Materials. Lab Animal 32:24-27.

Link to companion paper establishing that
bisphenol A induces aneuploidy even at low doses

Click here for an explanation of aneuploidy

Koehler et al. describe in this paper a laboratory accident that led to a dramatic new discovery about the harmful effects of bisphenol A (BPA), the molecule with which polycarbonate plastic is made.

The accident occurred in 1998, when a lab technician mistakenly used an extremely caustic detergent to clean out the water bottles and cages being used in the laboratories experiments on aneuploidy in mice.

Immediately following the technician's mistake, the incidence of hyperploidy shot up dramatically to over 8 times the background rate. adapted from Koehler et al.

The scientists also witnessed a 20-fold increase in chromosomal misalignments and 4+fold increase in death rate, disproportionately among younger mice. They also noted increases in reproductive tract tumors which had been exceedingly rare prior to the accident. Even after completely replacing cages and bottles, the incidence of aneuploidy and chromosomal aberrations did not fall back to the low levels prevailing prior to the accident.

Pre-accident levels returned only after moving the animal colony to a completely new facility.

Is this sort of accident rare? Not according to Koehler et al. They report that in discussions with colleagues at other labs they revealed "numerous anecdotal reports of unexplained changes in experimental results and of rapid, visible changes in caging materials." Indeed, as this paper was in press waiting for publication, another laboratory reported on bisphenol A leaching out of laboratory caging at levels sufficient to cause an estrogenic response.

Why is this important? Koehler's report is important for two reasons.

• First, it has revealed a hitherto unsuspected cause of aneuploidy, which is a known cause of a large percentage of spontaneous miscarriages and birth defects in people. Whether bisphenol A causes aneuploidy in people has yet to be confirmed, but there is no reason based on current understandings of the mechanisms of aneuploidy to conclude that it does not. To the contrary, available evidence indicates that it does. Exposure to bisphenol A is widespread in people and experienced at levels comparable to those that subsequent work by this laboratory proved were sufficient to cause aneuploidy in mice. These results thus strongly suggest that the appropriate public health response would be to immediately initiate steps to reduce human exposure to BPA.
• Second, inadvertent and undetected contamination of this sort in laboratory experiments is likely to cause many erroneous conclusions, and in particularly, to create circumstances for false negatives in the study of environmental toxicants. The result may be that many experiments have provided false assurances of safety about the health impacts of contaminants.
  [for more on this theme...]

Koehler et al. conclude that "the sheer volume of reports of disrupted experiments, in addition to the results from experimental tests of substances, such as BPA, that may be released from caging or other environmental materials, warrants immediate attention by the animal research community."