EPA priorities for biologic markers research in environmental health.

Recent advances in molecular and cellular biology allow for measurement of biologic events or substances that may provide markers of exposure, effect, or susceptibility in humans. The application of these new and emerging techniques to environmental health offers the possibility of significantly reducing the uncertainties that traditionally hamper risk assessments. The U.S. Environmental Protection Agency (EPA) health research program emphasizes the validation of appropriate biologic markers and their application to high-priority Agency issues. The rationale for EPA's biomarker research program is presented, and future research directions are discussed. Exposure biomarkers will receive most of the research emphasis in the near term, particularly body burden indicators of exposure to high-priority chemicals, such as benzene, ozone, selected heavy metals, and organophosphate pesticides. Research on effects biomarkers will attempt to validate the relationship between the observed biological effects and adverse health consequences in humans, especially for cancer, pulmonary toxicity, immunotoxicity, and reproductive/developmental toxicity.

Hospitalization decision in febrile intravenous drug users.

PURPOSE: To determine the frequency and to identify predictive factors of occult major illness in febrile intravenous drug users (IVDUs) presenting to an emergency room. PATIENTS AND METHODS: A prospective follow-up study was performed involving a consecutive series of 296 presentations of febrile IVDUs to a public hospital emergency room. Follow-up information was obtained for 283 presentations (95.6%). Physician's initial assessment was obtained for 204 presentations (70%). Illness was classified as major or minor using explicit criteria. Frequency of occult major illness was determined among patients without obvious major illness on presentation. Risk factors for occult major illness were determined. RESULTS: Occult major illness occurred in 11 patients (4%). This represented 11% of the 103 presentations without obvious major illness on presentation. Pneumonia and cellulitis occurred in 128 of 180 patients (71%) with obvious major illness on presentation. Bacteremia was present in seven of 11 patients with occult major illness. Physician predictions were not sufficiently sensitive to provide the basis of the hospitalization decision in febrile IVDUs. The best combination of features suggesting major illness were last use of intravenous drugs less than 5 days and fever greater than 38.8 degrees C (102.0 degrees F) (sensitivity 64%, specificity 77%). CONCLUSION: Clinical tests and physician assessments are unable to distinguish occult major illness from minor illness among febrile IVDUs at presentation. Occult major illness is best identified by blood culture. If patient follow-up is unreliable, then hospitalization of febrile IVDUs, while awaiting blood culture results, remains a wise policy.

Review of the mutagenicity of ethylene oxide.

Ethylene oxide has been shown to be an effective mutagen in a variety of organisms ranging from bacteria to mammalian cells. There is also an association between ethylene oxide exposure and human somatic cell cytogenetic damage. Furthermore, ethylene oxide has been shown to alkylate protein and DNA at exposure levels that have been encountered occupationally. Ethylene oxide is not only effective at producing somatic cell mutations but also at inducing genetic damage in germ cells. While it is clear that ethylene oxide is a germ cell mutagen in whole mammals, the mechanism(s) by which it produces genetic lesions in germ cells is uncertain.

Water disinfection: microbes versus molecules--an introduction of issues.

"Water is, apart from the air one breathes, the only nutrient which is, as a matter of necessity, consumed by every human being from the first day to the last day of his existence, and it is consumed in considerably larger quantities than any other nutritional substance."(1)

Comparative genetic mapping of cellular rel sequences in man, mouse, and the domestic cat.

We used in situ hybridization techniques to assign the human c-rel locus to the centromere-proximal portion of the short arm of chromosome 2 (2cent-2p13). We also determined the chromosomal location of c-rel sequences in the domestic cat and the laboratory mouse by using a human c-rel fragment to screen panels of rodent X cat and hamster X mouse somatic cell hybrid DNAs. The c-rel locus apparently maintains similar syntenic relationships with other known genetic markers in the human and cat, but displays different linkage relationships in the mouse.

Conserved chromosomal positions of dual domains of the ets protooncogene in cats, mice, and humans.

The mammalian protooncogene homologue of the avian v-ets sequence from the E26 retrovirus consists of two sequentially distinct domains located on different chromosomes. Using somatic cell hybrid panels, we have mapped the mammalian homologue of the 5' v-ets-domain to chromosome 11 (ETS1) in man, to chromosome 9 (Ets-1) in mouse, and to chromosome D1 (ETS1) in the domestic cat. The mammalian homologue of the 3' v-ets domain was similarly mapped to human chromosome 21 (ETS2), to mouse chromosome 16 (Ets-2), and to feline chromosome C2 (ETS2). Both protooncogenes fell in syntenic groups of homologous linked loci that were conserved among the three species. The occurrence of two distinct functional protooncogenes and their conservation of linkage positions in the three mammalian orders indicate that these two genes have been separate since before the evolutionary divergence of mammals.

Summary of in-house EPA workshop to define research/technical support approaches in biotechnology.

In summary. EPA is expanding its scientific capabilities in biotechnology in order to be able to provide better technical support for Agency decision-making. As part of this process, an in-house workshop was held to better define regulatory needs and necessary technical support. In building its program in biotechnology, emphasis will be placed on activities more related to the mission of EPA than that of any other Federal agency. Efforts will build upon past activities and will be coordinated with those of other Federal agencies. It is essential that EPA's scientific efforts in biotechnology be credible and defensible, and thus, its research plans will be subjected to expert peer review.