National Toxicology Program

The National Institute of Environmental Health Sciences (NIEHS) is one of the National Institutes of Health (NIH), and our primary mission is to reduce the burden of human illness and dysfunction from environmental exposures. Human health and human disease result from the interaction of our environmental exposures and our individual susceptibilities over time. We achieve our mission through multidisciplinary biomedical research programs conducted in our own laboratories and supported in laboratories around the country, prevention and intervention efforts, and communication strategies that encompass training, education, technology transfer, and community outreach. The NIEHS is also the lead agency for the Department of Health and Human Services' National Toxicology Program (NTP). The NTP coordinates toxicology research and testing activities within the Department to provide information about potentially toxic chemicals to regulatory and research agencies and the public, and to strengthen the science base for risk assessment. In its 18 years, the NTP has become the world's leader in designing, conducting and interpreting animal assays for toxicity.

On January 29, 1997, the Minnesota Pollution Control Agency (MPCA) Commissioner wrote to the Director, NIEHS, NIH, to request assistance with their ongoing investigation into the cause of frog malformations occurring across Minnesota. The Commissioner stated that this had become an environmental problem of national and international scope in which a great deal of public and scientific concern had been raised, including whether there could be any human health concerns in the many areas where the malformed animals have been found. A partnership was established with the MPCA, the lead agency in investigating this problem within Minnesota, and the NIEHS/NTP, the lead agency in performing chemical analysis and toxicology testing on samples from Minnesota. Dr. James Burkhart is the lead scientist on the NIEHS team and the main point of contact with Dr. Judy Helgen, the MPCA coordinator of these studies.

NIEHS/NTP PRELIMINARY FINDINGS

Field work began during the frog breeding season in July 1997. Water and sediment samples were collected from affected and unaffected ponds in Minnesota and were tested in the Frog Embryo Teratogenicity Assay-Xenopus (FETAX). This assay involves the exposure of developing embryos of Xenopus laevis for four days and then scoring the animals for malformations. What we know and don't know based on the preliminary findings from this laboratory work are:

• Water from ponds with a high incidence of malformed frogs induces a very high frequency of malformations in the FETAX.
• The effect is dose-dependent and reproducible.
• Water from ponds without malformed frogs does not induce these effects.
• Preliminary results suggest that similar effects are induced by groundwater and well water collected near the affected ponds.
• The frog used in FETAX is not the same as those occurring naturally in Minnesota.
• The water contaminant responsible for the effects observed in FETAX is not known.
• The human health implications of these results are not known although there is, in general, good agreement between the FETAX assay and rodent bioassays for birth defects. Rodent bioassays are often used for regulatory or public health decisions on environmental contaminants.
  

FUTURE COLLABORATIVE EFFORTS

Additional research is critical to confirm these early NIEHS/NTP findings and to understand what relationship, if any, these findings have to human health. NIEHS/NTP will continue to support the MPCA with the following collaborative efforts:

• Chemical analyses of water samples collected this summer are underway, and results should be available within two months. This will include: 1) analyses for a predetermined list of contaminants such as pesticides, metals, and organochlorines, and 2) broad spectrum analyses to determine all chemicals that may be present.
• Efforts to isolate and identify the contaminant(s) causing the effects will also include the fractionation of lake water and use of FETAX to track the biological activity, followed by chemical analysis.
• The FETAX assay will be used to assess all of the affected and unaffected ponds currently under study, as well as on additional well water samples collected near affected and unaffected ponds.
• An approach to studying the affected waters in standardized rodent teratogenicity assays is being considered.
• Evaluation of human health effects associated with living in the areas of affected ponds will be done in collaboration with epidemiologists from state and Federal agencies.

Given the widespread occurrence of malformed frogs nationally and internationally and the broad implications of the findings being generated through the Minnesota-NIEHS/NTP partnership, the NIEHS/NTP will, as soon as possible, organize a workshop to review the studies to date, research underway, and the plans for the future. The workshop will include representatives from the scientific community, state and Federal research and public health officials, and the public. The opportunity for public discussion, input, and comment will be provided.