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Biomedical subjects

R M Putzrath

Publications and source records attributed to R M Putzrath.

13 recordsLinked to original sources
PubMed2001

Children's health, susceptibility, and regulatory approaches to reducing risks from chemical carcinogens.

Risk-based regulation of chemical exposures from the environment generally relies on assumptions about the extent of people's susceptibility to chemically induced diseases. Those assumptions are intended to be health-protective; that is, they err on the side of overstating susceptibility. Recent concern about children's special susceptibilities has led to proposals that would make risk-based regulations one-tenth more stringent, unless data are available to refute the assumption that children are more susceptible than adults. In this paper we highlight some of the questions that should be addressed in the context of risk assessment to determine whether such increased stringency would accomplish the desired result of improving children's health. In particular, characterizing benefits of greater stringency requires more information about dose-response relationships than is currently available. Lowering regulatory levels has attendant costs but may not achieve benefits, for example, if the previous level were already below an actual or practical threshold. Without an ability to understand the potential benefit (or lack thereof) of the additional stringency, an appropriate consideration of benefits and costs is not possible.

Adult↗
PubMed2000

Reducing uncertainty of risk estimates for mixtures of chemicals within regulatory constraints.

Reducing uncertainty in estimated risks is always desirable. While regulatory assumptions and policies regarding risk assessment of chemicals can be debated, these are the rules under which many risk assessments are currently conducted. Methods for reducing the uncertainty in risk estimates generated under those rules are therefore useful, whether or not one agrees with the models and the underlying assumptions that comprise those rules. The guidance for risk assessment of mixtures of chemicals used by EPA was reexamined to determine methods for reducing the uncertainty in the cumulative risk estimates. It was found that the uncertainty could be significantly reduced if the assumptions concerning the assessment of mixtures of chemicals were combined with the assumptions for evaluating the risks of individual chemicals. Methods are proposed for reducing the uncertainty of mixtures of chemicals whose individual constituents are evaluated by cancer potency factors, hazard quotients, or margins of exposure. The methods developed do not require data beyond that which would be required for generating the current risk estimates for the individual chemicals. These analyses also demonstrated that some of the assumptions currently in use for regulatory risk assessment may lead to inconsistencies that should be reevaluated. As the proposed methods do not require any change in the current assumptions to reduce uncertainty in the risk estimates, the proposed methods should prove useful until such time as the assumptions are reevaluated and possibly changed.

Animals↗
PubMed1999

Fundamentals of health risk assessment. Use, derivation, validity and limitations of safety indices.

We investigated the way results of human health risk assessments are used, and the theory used to describe those methods, sometimes called the "NAS paradigm." Contrary to a key tenet of that theory, current methods have strictly limited utility. The characterizations now considered standard, Safety Indices such as "Acceptable Daily Intake," "Reference Dose," and so on, usefully inform only decisions that require a choice between two policy alternatives (e.g., approve a food additive or not), decided solely on the basis of a finding of safety. Risk is characterized as the quotient of one of these Safety Indices divided by an estimate of exposure: a quotient greater than one implies that the situation may be considered safe. Such decisions are very widespread, both in the U.S. federal government and elsewhere. No current method is universal; different policies lead to different practices, for example, in California's "Proposition 65," where statutory provisions specify some practices. Further, an important kind of human health risk assessment is not recognized by this theory: this kind characterizes risk as likelihood of harm, given estimates of exposure consequent to various decision choices. Likelihood estimates are necessary whenever decision makers have many possible decision choices and must weigh more than two societal values, such as in EPA's implementation of "conventional air pollutants." These estimates can not be derived using current methods; different methods are needed. Our analysis suggests changes needed in both the theory and practice of human health risk assessment, and how what is done is depicted.

Air Pollutants↗
PubMed1997

Estimating relative potency for receptor-mediated toxicity: reevaluating the toxicity equivalence factor (TEF) model.

Once considered and interim procedure for use with mixtures of polychlorinated dibenzo-p-dioxins and dibenzofurans, use of the toxicity equivalence factor (TEF) model has been proposed for other groups of structurally similar chemicals. Data from polychlorinated dibenzo p-dioxins and polychlorinated dibenzofurans as well as theoretical analyses of the biological basis for receptor-mediated toxicity demonstrate the limitations of this model and indicate that estimation of equivalent doses for such chemicals is more likely to require a function than a point estimate such as a TEF. Relatively small changes in the TEFs can result in both significant changes in the estimated dose for the mixture and the percentage of the estimated risk that is attributable to the most potent or reference compound. Estimates of equivalent doses are likely to become less accurate when extrapolated to lower responses which frequently serve as the basis for regulatory decisions. Existing models allow the relative potency to be a function rather than a point estimate as well as interaction at the receptor among the chemicals.

Benzofurans↗
PubMed1991

Meta-analysis: methods for combining data to improve quantitative risk assessment.

Although individual studies that constitute the data base for a risk assessment are each evaluated quantitatively as well as qualitatively, assessment of the total data base frequently results in selection of data from particular studies, rather than an effort to combine data quantitatively. Meta-analysis, or the analysis of analyses, provides an approach for the joint evaluation of the results of several studies. In this report, two very similar cancer bioassays of trichloroethylene were used to illustrate some simple meta-analytic techniques and to evaluate the validity and value of these procedures. The results demonstrate that concepts such as the upper 95% confidence limit are highly dependent upon assumptions if several data sets are involved. Use of a Monte Carlo procedure resulted in an increase in the 95% upper confidence limit relative to the value determined by EPA, but by determining the variance of the maximum likelihood estimate of the linear coordinate of the estimated dose-response curve, the 95% upper confidence limit of the cancer potency factor was reduced.

Dose-Response Relationship, Drug↗
PubMed1981

Inhibition of growth of Escherichia coli by lactose and other galactosides.

A study has been made of the inhibition of growth caused by the addition of lactose or other galactosides to lac constitutive Escherichia coli growing in glycerol minimal medium. The effect was greater at pH 5.9 and pH 7.9 than at pH 7.0. Inhibition of growth by lactose was observed also in the case of a beta-galactosidase negative mutant. However, a lacY mutant, which has a defect in the entry of protons normally coupled with galactoside transport, showed only slight inhibition of growth on the addition of galactosides. In the case of the parental strain the addition of lactose resulted in a sharp fall in delta pH across the cell membrane and a reduction in intracellular ATP, and the recovery was slow. Under the same conditions the lacY mutant showed a smaller and only transient effect. It is postulated that the sudden entry of protons associated with lactose uptake lowers the protonmotive force, reducing the ATP levels and inhibiting growth of the cells. This hypothesis would account also for the selection of lacY mutants found when E. coli is grown in the presence of isopropyl-beta-D-thiogalactoside.

Escherichia coli↗
PubMed1981

Analysis of mutagenic activity in cigarette smokers' urine by high performance liquid chromatography.

Mutagenic activity in smokers' urine which had been concentrated by XAD-2 resin can be separated from approximately 90% of the non-mutagenic material by CH2Cl2 extraction. This extract appears to be stable for 3 months at -20 degrees C. High performance liquid chromatography analysis of the CH2Cl2 extract showed multiple mutagenic non-polar fractions which were better activated by rat liver homogenates prepared from 3-methylcholanthrene treated rats than from rats treated with phenobarbital. Mutagenic activity in smokers' urine was extractable by acid, but not by base. The mutagens in smokers' urine appear to be a complex mixture of relatively non-polar chemicals.

Animals↗
PubMed1978

Properties of a persistent viral infection: possible lysogeny by an enveloped nonlytic mycoplasmavirus.

MVL2, an enveloped double-stranded DNA mycoplasmavirus, causes a nonlytic infection of Acholeplasma laidlawii leading to the establishment of a persistent infection. Persistently infected clones were found to be resistant to superinfection by homologous virus, but could be infected by heterologous virus. Cells in a persistently infected culture had the potential to produce virus and transmitted this potential as a stable heritable trait. Mitomycin C and UV light induced an increase in infectious centers in persistently infected cultures.

Acholeplasma laidlawii↗
PubMed1977

Growth of an enveloped mycoplasmavirus and establishment of a carrier state.

The growth of an enveloped DNA-containing mycoplasmavirus (MVL2 obtained from R.N. Gourlay) has studied, by using the indicator host Acholeplasma laidlawii strain JA1. From virus one-step growth curves, artificial lysis experiments, and infected cell growth curves, it was found that virus infection is nonlytic. Newly infected cells grow slower and are osmotically more stable than uninfected cells. However, 4 to 6 h after infection, the cells reach a carrier state in which cell growth rate and osmotic fragility are indistinguishable from uninfected cells. Carrier cultures contain free virus. Every carrier culture cell gives rise to either a clone of carrier cells or a clone of MVL2-resistant cells.

Acholeplasma laidlawii↗