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Biomedical subjects

L Zeise

Publications and source records attributed to L Zeise.

30 records · Page 2Linked to original sources
PubMed1991

Photoprotection by melanin.

This paper is an attempt to summarize the current state of information on melanin and epidermal melanin pigmentation (EMP) as photoprotective agents. The chemistry and biochemistry of melanin (the particle) and its interaction, in its various forms, with UV radiation are considered. Methods of attenuation of UV radiation are discussed in terms of structure and chemical constituents. Photoprotection by constitutive and facultative pigmentation is reviewed with minimum erythema dose (MED) as the end point. The issue of acclimatization to UV radiation is discussed in terms of UVB phototherapy for psoriasis. Finally, skin cancer is considered as an end point and the reduction of its incidence with pigment level is discussed. It is concluded that whilst EMP provides protection, its extent depends on the end point chosen for evaluation. MED is a convenient photobiological end point but is rather insensitive, whereas skin cancer is sensitive but impractical for laboratory studies. Our current state of knowledge of melanin lacks information on its absorption and scattering coefficients and its refractive index. Methods for the quantitative measurement of EMP are also urgently required.

Humans↗
PubMed1990

Route-dependent pharmacokinetics, distribution, and placental permeability of organic and inorganic selenium in hamsters.

Inorganic selenium (Se) salts (selenite and selenate oxyanions) and the organic selenoamino acids (selenomethionine and seleniferous grains) are teratogenic and embryolethal in domestic and wild birds. Selenium bioaccumulation has been held responsible for reproductive failure among waterfowl at the Kesterson Reservoir (California), the Ouray and Stewart Lake Wildlife Refuges (Utah), and the Carson Sink (Nevada). Anecdotal field and controlled laboratory reports have implicated Se exposure in mammalian embryotoxicity (including human), but developmental toxicity studies in hamsters failed to demonstrate an adverse response, except at maternally toxic doses (Ferm et al., Reprod. Toxicol., in press). Uptake, distribution, and elimination of Se after a single bolus equimolar dose (60 mumol/kg) of selenate or selenomethionine by oral or intravenous administration were compared using day 8 pregnant hamsters. Intravenous selenate was eliminated ten times more rapidly from maternal plasma than oral selenate, but concentrated in liver, kidney, and placenta to the same degree. Intravenous (iv) L-selenomethionine achieved lower maximum circulating total [Se], but it was eliminated more slowly than iv selenate. Larger areas under the plasma and peripheral tissue [Se]:time curve (AUC) after oral or parenteral selenomethionine than after equimolar selenate were consistent with previous studies in rodents and in humans. Embryonic [Se] plateaued at 3 nmol/g after selenate, but embryonic [Se] after selenomethionine continued to accumulate (80 nmol/g) as gestation progressed. The lack of a teratogenic response in hamsters at doses of either selenate or selenomethionine less than those associated with maternal intoxication cannot be attributed to lack of Se accumulation in early embryonic and placental tissue.

Animals↗
PubMed1990

Precision and sensitivity of pharmacokinetic models for cancer risk assessment: tetrachloroethylene in mice, rats, and humans.

Pharmacokinetic analyses have recently been incorporated in risk assessments, with resultant risks sometimes lower and associated "allowable" exposures higher, than would have been otherwise calculated. Predictions of coupled pharmacokinetic and multistage models, as used for regulatory purposes, are evaluated here for tetrachloroethylene carcinogenicity in mice, rats, and humans. Precision is studied by treating parameters as random variables and determining the range of risk estimates once parameter uncertainties are considered via Monte Carlo simulations. The methods developed in this study are of interest for any similar application. The resultant median risk estimate for humans exposed continuously to 1 ng/liter of tetrachloroethylene in the air is 1.6 per million and 5, 25, 75, and 95 percentiles are 0, 0.04, 2.8, and 6.8 per million. Sensitivity of the pharmacokinetic model predictions to its parameters is assessed by analyzing the results of the Monte Carlo simulations. The kinetic parameters defining the metabolic rate are the most important for the case studied.

Animals↗
PubMed1990

Risk assessment for carcinogens under California's Proposition 65.

Risk assessments for carcinogens are being developed through an accelerated process in California as a part of the state's implementation of Proposition 65, the Safe Drinking Water and Toxic Enforcement Act. Estimates of carcinogenic potency made by the California Department of Health Services (CDHS) are generally similar to estimates made by the U.S. Environmental Protection Agency (EPA). The largest differences are due to EPA's use of the maximum likelihood estimate instead of CDHS' use of the upper 95% confidence bounds on potencies derived from human data and to procedures used to correct for studies of short duration or with early mortality. Numerical limits derived from these potency estimates constitute "no significant risk" levels, which govern exemption from Proposition 65's discharge prohibition and warning requirements. Under Proposition 65 regulations, lifetime cancer risks less than 10(-5) are not significant and cumulative intake is not considered. Following these regulations, numerical limits for a number of Proposition 65 carcinogens that are applicable to the control of toxic discharges are less stringent than limits under existing federal water pollution control laws. Thus, existing federal limits will become the Proposition 65 levels for discharge. Chemicals currently not covered by federal and state controls will eventually be subject to discharge limitations under Proposition 65. "No significant risk" levels (expressed in terms of daily intake of carcinogens) also trigger warning requirements under Proposition 65 that are more extensive than existing state or federal requirements. A variety of chemical exposures from multiple sources are identified that exceed Proposition 65's "no significant risk" levels.

Animals↗
PubMed1989

Chromium carcinogenicity: California strategies.

Hexavalent chromium was identified by California as a toxic air contaminant (TAC) in January 1986. The California Department of Health Services (CDHS) concurred with the findings of the International Agency for Research on Cancer that there is sufficient evidence to demonstrate the carcinogenicity of chromium in both animals and humans. CDHS did not find any compelling evidence demonstrating the existence of a threshold with respect to chromium carcinogenesis. Experimental data was judged inadequate to assess potential human reproductive risks from ambient exposures. Other health effects were not expected to occur at ambient levels. The theoretically increased lifetime carcinogenic risk from a continuous lifetime exposure to hexavalent chromium fell within the range 12-146 cancer cases per nanogram hexavalent chromium per cubic meter of air per million people exposed, depending on the potency estimate used. The primary sources found to contribute significantly to the risk of exposure were chrome platers, chromic acid anodizing facilities and cooling towers utilizing hexavalent chromium as a corrosion inhibitor. Evaluation of genotoxicity data, animal studies and epidemiological studies indicates that further consideration should be given to the potential carcinogenicity of hexavalent chromium via the oral route.

Air Pollutants↗
PubMed1989

Application of clearance concepts to the assessment of exposure to lead in drinking water.

This paper explores the application of clearance concepts to environmental toxicology. Lead, for which a clearance of about 0.5 ml/min is estimated from published data, is chosen as an example. An index for the contribution of drinking water to total exposure is developed using these concepts. For lead, this index is shown to increase with the concentration of the metal in water; it is higher for children than for adults. At the maximum contaminant level (MCL) of 10 micrograms/L proposed by the US Environmental Protection Agency (EPA), the average contribution from lead in drinking water is estimated to be 7 percent. The contribution in children is about twice as great. At and above the current MCL of 50 micrograms/L, drinking water becomes a major source of lead exposure.

Adult↗
PubMed1988

Sunlight, melanogenesis and radicals in the skin.

Melanocytes are cells of neural crest origin residing at the dermal-epidermal juncture. They produce specialized organelles called melanosomes within which the biochemical processes of melanization occurs. UV radiation is capable of inducing melanogenesis and, during the biosynthesis of melanins, several of the putative precursors "leak out" of the melanosome and can be detected in the skin, serum and urine of individuals undergoing active melanogenesis. Most notable are the cysteinyldopas (formed by nucleophilic addition of cysteine to dopaquinone) and several dihydroxyindoles (formed by intramolecular cyclization of dopaquinone). These catechols often are methylated in the melanocyte to afford a mixture of the monomethoxy derivatives and, in some cases, the dimethoxy species. Recent investigations in our laboratories have demonstrated that the cysteinyldopas, dihydroxyindoles, and their various methylated derivatives are photochemically unstable. Irradiation with biologically relevant ultraviolet radiation (i.e. wavelengths greater than 300 nm) results in the rapid destruction of the precursors/metabolites and the production of a variety of free radical species. The photochemistry and potential photobiological significance of melanogenic intermediates is discussed.

Free Radicals↗
PubMed1987

Tautology or not tautology?

It has been suggested that the good correlations found between carcinogenic potency in mice and in rats could be an artifact. The artifact suggested arises because there are four correlations to consider--interspecies correlations of toxicity, interspecies correlations of carcinogenic potency, and two intraspecies correlations between toxicity and carcinogenic potency--and the existence of any three implies the fourth. It was argued that the intraspecies correlations between toxicity and potency were due to criteria for data selection. Here we discuss the correlations in detail and show that they are principally due to the experimental observation that there are few cases where most or all animals in a bioassay get cancer. We conclude that the correlations between carcinogenic potency are valid.

Animals↗
PubMed1987

Dose-response relationships for carcinogens: a review.

We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinearities. There are few experimental examples of nonlinear dose-response relations in humans, but this may simply be due to the limitations in the data. The several examples in rodents, even though for high dose data, suggest that nonlinearity is common. In some cases such nonlinearities may be rationalized on the basis of the pharmacokinetics of the test compound or its metabolites.

Animals↗
PubMedDate not supplied

Role of exposure databases in risk management.

Despite the development of numerous national exposure-related databases, exposure assessment remains a weak link in the chain of risk assessment and risk-management activities. Most databases include measures of environmental releases or concentrations of pollutants in specific media, but do not include actual measures of exposure. If accurate estimates of exposure experienced by populations or individuals are absent, it is impossible to judge the effectiveness of risk-management strategies. The Risk Management Work Group evaluation identified the following needs: refinement of measurements of total exposure experienced by individuals, improved characterization of the distribution of exposures in the population, longitudinal monitoring of exposure trends, and improved information about the public health implications of exposure. Recommendations are presented with the hope that the utility of existing databases will be improved and that future initiatives will be developed that meet the needs of risk management.

Databases, Factual↗