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Biomedical subjects

E J Calabrese

Publications and source records attributed to E J Calabrese.

At least 199 records · Page 11Linked to original sources
PubMed1979

Effects of environmental oxidant stressors on individuals with a G-6-PD deficiency with particular reference to an animal model.

Individuals with a G-6-PD deficiency have long been known to be at increased risk to experience acute hemolysis following exposure to elevated levels of certain oxidant drugs and industrial chemicals. However, the recognition of enhanced susceptibility to environmental (or ambient) pollutants has generally not been considered. Recent theoretical studies have suggested that elevated levels of ambient ozone may be an etiologic factor in the onset of acute hemolysis in the G-6-PD deficient individual. Furthermore, the proposed usage of either chloramines or chlorine dioxide as replacements for chlorine for the disinfection of drinking water should be investigated with respect to their potential adverse effects of individuals at increased risk to oxidant stressors. In order to test these theoretical associations, two mouse strains, one with low and the other with high levels of G-6-PD activity in their red blood cells are being investigated to determine if they simulate human G-6-PD deficient and normal individuals, respectively. Preliminary results indicate that the mouse strain with low G-6-PD activity is markedly more susceptible to sodium chlorite than mice of the high G-6-PD strain. This differential susceptibility to sodium chlorite toxicity between the high and low G-6-PD mouse strains suggests that further research designed to validate the efficacy of this mouse model as a predictor of the human situation is warranted.

Air Pollutants↗
PubMed1977

Further comments on novel schedule TLVs.

The general formula approach for the development of TLVs for novel work schedules represents a reasonable first attempt in dealing with this new industrial health problem. However, several additional factors should be considered in the derivation of novel work schedule TLVs. They include: 1. the individuals who are at increased risk with respect to the pollutant in question; 2. the possible influences of rotational changes and disrupted circadian rhythms on health status of workers adopting the proposed novel schedules; 3. the type of toxicologic response to be affected and the degree of safety margin built into the TLV; 4. the metabolic rate and fate of the substance in the individual.

Carcinogens↗
PubMed1977

The health implications of open leaf burning.

Because leaf burning emissions contain polycyclic aromatic hydrocarbon compounds which have varying potential for causing cancer in animals; because carcinogenesis in one or more animal species creates a strong index of suspicion that the same chemical will be carcinogenic for humans; because safe levels for human exposure to chemical carcinogens cannot be predicted on the basis of animal or epidemiological data; and finally, because it is impossible to quantify the human risk of developing cancer to which leaf burning might contribute, it is both unwise and dangerous to permit the further contamination of the environment by chemical carcinogens from leaf burning emissions.

Air Pollutants↗
PubMedDate not supplied

Possible examples of chemical hormesis in a previously published study.

A re-examination of data presented by Daston et al. provided an opportunity to assess the occurrence of chemical hormesis due to the wide dosage range tested and to the large number of treatments within the dosage range. The data revealed numerous examples of possible chemical hormesis for a variety of end-points measured.

Animals↗
PubMedDate not supplied

Decrease in hepatotoxicity by lead exposure is not explained by its mitogenic response.

The present research was conducted to evaluate the effect of mitogen pre-exposure on CCl4-induced hepatotoxicity. Male Wistar rats were administered a single i.p. injection of CCl4 (0.3 ml kg-1 in corn oil) 48 h following either a single dose of lead nitrate (0.33 mg kg-1) or distilled water via i.v. injection. Hepatotoxicity, as measured by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, was monitored 6, 24, 48, 72 and 120 h after CCl4 exposure. The lead nitrate-pretreated rats displayed markedly lower serum ALT and AST levels at 24, 48 and 72 h than rats pretreated with distilled water. However, treatment with the antimitotic agent colchicine did not alter the lead-induced protection. These findings suggest that the lead-induced protection is not associated with the major mitogenic response of lead, despite its strong temporal association. A critical review of the available toxicological data also argues against the lead protection being a function of its capacity to inhibit cytochrome P-450.

Alanine Transaminase↗
PubMedDate not supplied

Potency ranking of methemoglobin-forming agents.

This study represents the first systematic attempt to rank methemoglobin-forming agents. It is a quantitative potency ranking study utilizing linear regression analysis of dose-response data for comparative purposes. Six agents that are direct-acting and eight that require bioactivation were tested for their ability to induce methemoglobin formation in Dorset sheep erythrocytes under defined in vitro conditions. The agents were then ranked according to three complementary methods based on the slope of the linear regression, the calculated dose expected to induce a given amount of methemoglobin formation and the calculated percentage methemoglobin response induced by 1 mmol l-1 of the agent. The direct-acting agents, ranked from most to least potent inducers of methemoglobin formation, are: p-dinitrobenzene > o-dinitrobenzene > copper = nitrite > chlorite > chlorate. The ranking from most to least potent inducers of the bioactivated agents are: alpha-naphthol > p-nitroaniline > m-nitroaniline, o-nitroaniline > p-nitrotoluene = aniline > m-nitrotoluene = o-nitrotoluene. The ranking procedures are discussed and issues of interindividual variation and agent-specific sensitivities are addressed.

Analysis of Variance↗
PubMedDate not supplied

Is EPA's radium-226 drinking water standard justified?

The U.S. Environmental Protection Agency's (EPA) proposed drinking water standard for radium-226 (226Ra) of 5 pCi/l is evaluated according to its health basis and carcinogenic implications. Proposed health risks of 226Ra in drinking water by other leading theoreticians (Evans, Gofman-Tamplin and Peterson) are also considered in light of the EPA proposal. It is concluded that the EPA proposal to raise the standard for 226Ra in drinking water is not justified on the basis of present knowledge of 226Ra carcinogenic effects.

Body Burden↗
PubMedDate not supplied

Environmental quality induced predicted by evolutionary theory.

The use of evolutionary theory to understand and predict environmental quality indices has been described. Three specific examples concerning the environmental health implications of black skin, heat stress adaptation, and G-6-PD deficiency have been discussed in which evolutionary theory provides the conceptual framework for novel insights and reasonable predictions of environment, pollutant and human interactions. The use of the evolutionary paradigm in the development of environmental quality indices offers a clear alternative to trial and error research efforts.

Biological Evolution↗
PubMedDate not supplied

Insufficient conjugate glucuronidation activity: a possible factor in polychlorinated biphenyl (PCB) toxicity.

Considerable evidence indicates that phenolic and biphenolic compounds are detoxified and excreted primarily via conjugate glucuronidation in man. Since fetuses, neonates and certain enzyme deficient adults have significant functional deficiencies in their capacities to excrete toxic compounds via conjugate glucuronidation, it is predicted that these groups of individuals are biochemically predisposed to accumulate polychlorinated biphenyls (PCB's), a widely distributed and highly toxic environmental contaminant.

Animals↗
PubMedDate not supplied

Will elevated levels of lead exposure precipitate clinical symptoms of porphyria in individuals with the latent condition?

Individuals with excessive activity of the enzyme ALA-S due to either inherited disorder (i.e. porphyrias) or endogenous (i.e. steroids) or exogenous (e.g. barbituates) chemical agents and who are exposed to elevated levels of lead are predicted to have a significantly enhanced likelihood of experiencing either enhanced or precipitated clinical symptoms (e.g. photosensitivity) associated with elevated levels of porphyrins or their precursors in body tissues. In light of the widespread societal use of ALA-S inducing agents and the ubiquitous nature of lead in the environment, a more precise assessment of the health risks associated with their interaction is warranted.

5-Aminolevulinate Synthetase↗
PubMedDate not supplied

Potential health effects of chlorine dioxide as a disinfectant in potable water supplies.

Chlorination of potable water supplies high in organics may yield carcinogenic compounds such as trihalomethanes. Chlorine dioxide has been proposed as an alternative disinfectant to chlorine. However, chlorine dioxide is a strong oxidant that forms significant amounts of chlorite when added to potable water supplies, and chlorite is similar to nitrite in its molecular structure and may be similar in its mechanism of methemoglobin production. Nitrites and chlorites are thought to act synergistically to produce MetHb. Neonates and persons with G-*-PD deficiency are likely to be unusually susceptible to MetHb formation from these compounds because their red cells lack the metabolic machinery to adequately protect against oxidant stress. Since male blacks represent the largest population in the U.S. to be G-6PD deficient, Black male neonates may represent the group at highest risk to the use of chlorine dioxide as a disinfectant in the nations water supplies.

Adult↗
PubMedDate not supplied

Does ambient ozone pose a serious public health concern as a widespread environmental mutagen?

Based on bacterial, plant, animal and human studies, it is evident that O3 is a general mutagen. However, there is still considerable uncertainty as to the extent to which O3 is a human mutagen. Attempts to develop dose-response relationships have not yielded consistent results in the several studies thus far reported. At the present time there is a complete lack of data concerning human responses from ambient exposure. In light of the extent of the photochemical oxidant problem in the U.S. and the potential genetic effects of O3, it is suggested that a major research effort be directed at both the elucidation of the potential mutagenic effects of O3 as well as the implementation of effective oxidant control strategies.

Animals↗