Dietary vitamin D3 restriction influences tumor growth, but not the ability to generate an antigen-specific immune response in OTII transgenic mice.

Initially, we wanted to know whether dietary vitamin D(3) restriction would influence growth and metastasis of the 4T1 murine mammary carcinoma. We confirmed serum 25(OH)D levels were modulated by dietary vitamin D(3) restriction, mice were healthy, and when challenged with the 4T1 tumor alterations in tumor growth, but not metastasis were evident. Tumors grew more rapidly in mice on the vitamin D(3) restricted diet. To delineate whether dietary vitamin D(3) restriction influenced the ability to generate an antigen-specific immune response we used OTII transgenic mice which express a T cell receptor specific for ovalbumin. We found that dietary vitamin D(3) restriction did not influence the health of OTII mice, the number of circulating CD3/CD4(+), CD3/CD8(+), CD4/CD25(+) T cells, nor the ability to generate CD11c(+) bone-marrow derived dendritic cells. T cells from OTII mice maintained on the vitamin D(3) restricted diet also exhibited no significant alterations in proliferative capacity or ability to secrete IFN-gamma or IL-4 in an antigen-specific manner. Yet, EL-4 tumors grew more rapidly in OTII mice on the vitamin D(3) restricted diet. These data show that dietary vitamin D(3) restriction impacts tumor growth, but not the ability to generate an antigen-specific immune response.

Early effects of low benzene exposure on blood cell counts in Bulgarian petrochemical workers.

OBJECTIVES: Only few studies have examined early hematological effects in human populations exposed to low benzene levels and their findings are controversial. We evaluated hematological outcomes (WBC, neutrophils, lymphocytes, monocytes, eosinophils, basophils, RBC, Hb, HCT MCV, platelets and MPV) in a population of 153 Bulgarian petrochemical workers exposed to benzene (range 0.01-23.9 ppm) and 50 unexposed subjects. METHODS: Written informed consent was obtained and a self-administered questionnaire used to collect information on current smoking habits, lifestyle, and occupational activities. Exposure assessment was based on personal monitoring sampling the day before phlebotomy. Urinary trans-trans-muconic acid (t,t-MA) was determined at the beginning and end of the work shift. Based on individual airborne benzene measurements, study subjects were categorized in three exposure categories (referents, <1 and > or =1 ppm). Mean values of each hematologic outcomes in each exposure category were compared with the referent group using a multiple linear regression model adjusted for age, gender, current smoking habits and environmental toluene level. The influence of the CYP2E1 (RsaI and DraI) and NQO1 609C>T genetic polymorphisms on differential hematological parameters was also investigated. RESULTS: No dose-response effect was observed for most of the examined hematological outcomes (WBC, lymphocytes, neutrophils, monocytes, RBC, Hb, HCT, MCV, platelets and MPV). The eosinophil count was inversely related to benzene exposure only among smokers. Conversely, basophils increased with increasing exposure. No effect on benzene hematotoxicity was found for any of the investigated polymorphisms. CONCLUSION: In our study we did not find a decline in WBC and lymphocytes related to benzene exposure. A myeloproliferative effect of benzene is highly unlikely to explain the observed reduction in eosinophils and increase in basophils as it would lead to a concordant depression in all granulocyte subpopulations. Whether benzene effects at low doses are present in Caucasian populations remains uncertain, thus warranting further investigations.

The precautionary principle also applies to public health actions.

The precautionary principle asserts that the burden of proof for potentially harmful actions by industry or government rests on the assurance of safety and that when there are threats of serious damage, scientific uncertainty must be resolved in favor of prevention. Yet we in public health are sometimes guilty of not adhering to this principle. Examples of actions with unintended negative consequences include the addition of methyl tert-butyl ether to gasoline in the United States to decrease air pollution, the drilling of tube wells in Bangladesh to avoid surface water microbial contamination, and villagewide parenteral antischistosomiasis therapy in Egypt. Each of these actions had unintended negative consequences. Lessons include the importance of multidisciplinary approaches to public health and the value of risk-benefit analysis, of public health surveillance, and of a functioning tort system-all of which contribute to effective precautionary approaches.

Science, policy, stakeholders, and fish consumption advisories: developing a fish fact sheet for the Savannah River.

In recent years there has been a startling rise in the issuance of fish consumption advisories. Unfortunately, compliance by the public is often low. Low compliance can be due to a number of factors, including confusion over the meaning of advisories, conflicting advisories issued by different agencies, controversies involving health benefits versus the risks from consuming fish, and an unwillingness to act on the advisories because of personal beliefs. In some places, such as along the Savannah River, one state (South Carolina) had issued a consumption advisory while the other (Georgia) had not, although at present, both states now issue consumption advisories for the Savannah River. Herein we report on the development of a fish fact sheet to address the confusing and conflicting information available to the public about consuming fish from the Savannah River. The process involved interviewing fishers to ascertain fishing and consumption patterns, evaluating contaminant levels and exposure pathways, discussing common grounds for the provision of information, and consensus-building among different regulatory agencies (US Environmental Protection Agency, South Carolina Department of Health and Environmental Control, Georgia Department of Natural Resources) and the Department of Energy. Consensus, a key ingredient in solving many different types of "commons" problems, was aided by an outside organization, the Consortium for Risk Evaluation with Stakeholder Participation (CRESP). The initial role for CRESP was to offer scientific data as a basis for groups with different assumptions about risks to reach agreement on a regulatory response action. The process was an example of how credible science can be used to implement management and policies and provide a basis for consensus-building on difficult risk communication issues. The paper provides several lessons for improving the risk process from stakeholder conflicts, through risk assessment, to risk management. It also suggests that consensus-building and risk communication are continuing processes that involve assimilation of new information on contaminants and food-chain processes, state and federal law, public policy, and public response.

Environmental risks and public health.

There are currently a number of initiatives aimed at considering and redefining the role of environmental health. These include an effort under the auspices of the Institute of Medicine Roundtable on Environmental Health and another under the auspices of the American Schools of Public Health. Both will result in conferences to be held in the same month of the New York Academy of Sciences (NYAS) conference on "The Role of Neural Plasticity in Chemical Intolerance", for which this paper is being prepared. This questioning of our definition and of our approach to the field of environmental health is an instructive background on which to consider the issue of environmental risks and public health-the topic given to me by the organizers of the NYAS conference. My approach will be to touch on those issues related to the nervous system and to unexplained symptoms in keeping with the subject of the conference, as well as to discuss some of the broader issues surrounding environmental health.

The precautionary principle and scientific research are not antithetical.

The Precautionary Principle is intended to protect human health and the environment. To serve these goals effectively, precautionary action must be coupled with concurrent research to decide whether the action taken is in fact protective.

Lessons in environmental health in the twentieth century.

Environmental health has evolved rapidly in recent decades, drawing largely on new analytic technologies, advanced data acquisition and modeling, mechanistic studies in toxicology, and the conceptual framework of risk assessment. The latter combines toxicologic and epidemiologic data with improved techniques for quantifying exposure, producing estimates of risks from environmental hazards or conditions to selected target populations. The public and governments have become increasingly concerned with environmental health and quality. The major lessons have been (a) environmental-health scientists must participate in policy debates; (b) environmental health problems are exceedingly complex and require interdisciplinary research; and (c) environmental health is a global issue. The globalization of commerce, the untested impact of international trade agreements, increased migration, and especially increased population, have profound impact on the quality as well as availability of air, water, land, and food. Global atmospheric transport of pollutants and the effect on atmosphere and climate are two examples of globalization of environmental health.

Size characteristics of larger academic human environmental health programs in the United States.

We have performed a benchmark exercise evaluating larger academic programs in human environmental health sciences. These programs are located at schools of public health and at other institutions that have NIEHS Centers of Excellence. The largest programs were those in which there was both an NIEHS center and a public health graduate education program. This suggests that there is synergy between environmental health sciences research and involvement in public and community health.

A public health context for residual risk assessment and risk management under the clean air act.

The 1990 amendments to the Clean Air Act required the EPA to institute new pollution control technology requirements for industrial sources of air pollution. In part because agreement could not be reached on the best way for the EPA to determine whether any significant risks to human health will remain after the technology controls are in place, the amendments also created a Commission on Risk Assessment and Risk Management and gave the commission a broad mandate to review and make recommendations concerning risk assessment and risk management in federal regulatory programs. In its March 1997 final report to Congress and the administration, the commission recommended a tiered approach to assessing such residual risks. That approach included the idea that when decisions about managing residual risks are made, emissions should be evaluated in the context of other sources of air pollution. Evaluating risks in their larger contexts is consistent with what the commission called a public health approach to environmental risk management. This paper describes the public health approach and how it applies to evaluating residual risks under the Clean Air Act.

Capsaicin's effect on rat nasal mucosa substance P release: experimental basis for vasomotor rhinitis treatment.

Substance P (SP) is one of several neuropeptides found in nasal mucosa. It exists primarily in sensory afferent neurons, which are best demonstrated by immunohistochemical staining. These substance P-like immunoreactive (SPLI) nerve fibers are unmyelinated C fibers, which connect to the trigeminal ganglion and the spinal trigeminal nucleus. They are found around vessels and seromucinous glands in the submucosa. When the nasal mucosa receives a noxious stimulus, SP is released and acts orthodromically as a comediator of nasal pain, while antidromically it induces vasodilatation, plasma extravasation, mucosal edema, and rhinorrhea. Its antidromic effects have been implicated in vasomotor rhinitis and can be blocked by topical intranasal capsaicin application. Wolf and others have demonstrated in human subjects that vasomotor rhinitis can be blocked up to 1 year by a series of intranasal capsaicin applications. It has not yet been demonstrated that nasal mucous SP levels following noxious nasal stimulus change after intranasal capsaicin pretreatment. Consequently a project was designed to determine whether intranasal capsaicin pretreatment would affect nasal substance P release measured in nasal secretion. Nasal secretion SP levels were measured before and after noxious nasal stimulus in controls and in capsaicin pretreated rats. The difference in measured nasal secretion SP levels were significant (p < 0.05).

12th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals: susceptibility to environmental hazards.

The 12th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC) considered the topic of methodologies for determining human and ecosystem susceptibility to environmental hazards. The report prepared at the meeting describes measurement of susceptibility through the use of biological markers of exposure, biological markers of effect, and biomarkers directly indicative of susceptibility of humans or of ecosystems. The utility and validity of these biological markers for the study of susceptibility are evaluated, as are opportunities for developing newer approaches for the study of humans or of ecosystems. For the first time a SGOMSEC workshop also formally considered the issue of ethics in relation to methodology, an issue of particular concern for studies of susceptibility.

Dynorphin-(1-8) inhibits the release of substance P-like immunoreactivity in the spinal cord of rats following a noxious mechanical stimulus.

This study was conducted to determine the effect of the opioid peptide dynorphin-(1-8) on the release of substance P-like immunoreactivity in the dorsal horn during mechanical activation of peripheral nociceptors. A push-pull cannula was used to perfuse the dorsal horn of decerebrate/spinal transected rats before, during and following the application of a noxious mechanical stimulus to the ipsilateral hindpaw and lower limb. The collected perfusates were assayed for substance P-like immunoreactivity using radioimmunoassay. Dynorphin-(1-8) applied to the spinal cord at a concentration of 1 microM reduced the basal release of substance P-like immunoreactivity by 28 +/- 11% and prevented the mechanically evoked release of substance P-like immunoreactivity. This effect of dynorphin-(1-8) was reversed by 2 microM of the selective kappa-opioid receptor antagonist nor-binaltorphimine. Moreover, blockade of the kappa-opioid receptors by nor-binaltorphimine resulted in a 33 +/- 5% increase in the basal release of substance P-like immunoreactivity. These data show that activation of nor-binaltorphimine-sensitive sites by dynorphin-(1-8) results in inhibition of the release of substance P-like immunoreactivity in the dorsal horn of the rat.