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D Hattis

Publications and source records attributed to D Hattis.

25 records · Page 2Linked to original sources
PubMed1990

Analysis of dose/time/response relationships for chronic toxic effects: the case of acrylamide.

This case study illustrates how a very simple dynamic modeling approach can extract information of interest for both toxic mechanism research and risk assessment from a series of dose/time/response data. The technique is applicable for effects that are thought to result from damage processes that are reversible, at least at low doses and times of exposure. The data sets analyzed provided information on some specific manifestation of acrylamide neurotoxicity produced by different combinations of acrylamide dose rate and duration of exposure. Assuming that responses occur when a specific amount of axonal damage accumulates, and that the repair of damage depends directly on the amount of damage present, the dose-related change in the time required to produce a specific type of effect can be used to estimate: (1) The rate of repair of the incipient damage - and differences in repair rates for different individuals within species, and among different species, and (2) The dose of acrylamide that would be just barely able to produce each effect in each species, if the experiment were conducted over the animal's entire lifespan. Information of the first type may also be helpful in neurotoxicology research. Specific biomarkers for the main process causing a particular response should be repaired in different locations and in different species with the dynamics that are consistent with the repair rates calculated from the dose vs. time-of-effect data.

Acrylamide↗
PubMed1987

Human variability in susceptibility to toxic chemicals--a preliminary analysis of pharmacokinetic data from normal volunteers.

The tenfold "uncertainty" factor traditionally used to guard against human interindividual differences in susceptibility to toxicity is not based on human observations. To begin to build a basis for quantifying an important component of overall variability in susceptibility to toxicity, a data base has been constructed of individual measurements of key pharmacokinetic parameters for specific substances (mostly drugs) in groups of at least five healthy adults. 72 of the 101 data sets studied were positively skewed, indicating that the distributions are generally closer to expectations for log-normal distributions than for normal distributions. Measurements of interindividual variability in elimination half-lives, maximal blood concentrations, and AUC (area under the curve of blood concentration by time) have median values of log10 geometric standard deviations in the range of 0.11-0.145. For the median chemical, therefore, a tenfold difference in these pharmacokinetic parameters would correspond to 7-9 standard deviations in populations of normal healthy adults. For one relatively lipophilic chemical, however, interindividual variability in maximal blood concentration and AUC was 0.4--implying that a tenfold difference would correspond to only about 2.5 standard deviations for those parameters in the human population. The parameters studied to date are only components of overall susceptibility to toxic agents, and do not include contributions from variability in exposure- and response-determining parameters. The current study also implicitly excludes most human interindividual variability from age and illness. When these other sources of variability are included in an overall analysis of variability in susceptibility, it is likely that a tenfold difference will correspond to fewer standard deviations in the overall population, and correspondingly greater numbers of people at risk of toxicity.

Hazardous Waste↗
PubMed1986

Genetically-engineered microorganisms: I. Identification, classification, and strain history.

We have argued that accurate identification of the microorganism will form a cornerstone of the assessment of potential hazard. Appropriate methodology for identification exists, and is continually under development and refinement. Organizations such as the American Type Culture Collection will perform certified identifications for relatively low cost. Thus there appears to be little reason that an organism should not be identified insofar as current microbiology allows prior to submission for PMN review. We suggest that a complete microbiological characterization be considered an essential element of an acceptable PMN. To accomplish this, however, current institutional arrangements for the protection of trade secret information needed in the process of identification may need to be improved. An accurate identification of the strain will often provide access to important information with which to evaluate its ecology, pathogenicity, biochemistry, and genetics. Specialized texts, the scientific literature, and professional consultation are ready sources of such information. However, a major effort should be made to establish a data base that can specifically address the needs of biohazard evaluation. This could be done, in part, by collecting information about the construction, and about the behavior in the environment of genetically-engineered microorganisms that are now under development and will soon be tested or used. Identification information may also eventually be useful for the formulation of hypotheses about possible modes of harm or about relative safety, based on phylogenetic relationships. This is a very difficult undertaking at present, however. Microbial taxonomy is currently in a process of radical reevaluation as new macromolecular sequence information reveals previously unsuspected phylogenetic relationships, and disturbs categorizations based on older types of traits such as morphology, etc. This means that both inferences about relative safety and about possible modes of harm from taxonomic relationships must be highly tentative based on current information. Regulatory authorities may wish to consider requesting confirmatory DNA hybridization data or other macromolecular sequence comparisons in cases where strong arguments related to safety must be made from taxonomic information in relatively poorly studied groups of organisms. Detailed strain histories would provide valuable information for safety evaluations.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗
PubMed1981

Needs for public health intervention and needs for new research on vinyl halides and their polymers: a public policy perspective.

Consideration of needs for public health interventions and new research requires comparative assessments of the health benefits that are likely to result from alternative uses of limited regulatory and technical resources. This paper briefly examines regulatory and research priorities in the light of recent information on the carcinogenic hazards of vinyl chloride and alkyl and vinyl halides related to vinyl chloride, the respiratory-system hazards of poly (vinyl chloride), and the reproductive hazards of vinyl chloride. Specific suggestions are made for relatively promising types of efforts in these areas.

Female↗
PubMedDate not supplied

Risk assessment and management of chemical contaminants in fishery products consumed in the USA.

In the USA a small proportion of fishery products are contaminated with appreciable amounts of potentially hazardous contaminants. However, risks to consumers are not generally high. Inorganic contaminants with the greatest potential for toxicity are antimony, arsenic, cadmium, lead, mercury, selenium and sulfites. Among organic compounds, polychlorinated biphenyls, dioxins, several chlorinated hydrocarbon insecticides, certain processing-related and aquaculture-related contaminants pose potential risks for consumers. Log-normal distributions appear to provide good descriptions of the pattern of variation of contaminant concentrations among different geographic areas, and some contaminants (mostly organic) appear to be much more variable than others. This variability offers a solution for reduction of exposure through restricting the harvest of aquatic organisms from specific sites, and by excluding certain species. It is recommended that: (i) existing State and Federal regulations and environmental monitoring be strengthened and enforced to minimize contamination of the aquatic environment; (ii) a program of shared responsibility be instituted, where Federal agencies develop a set of monitoring and inspection practices and state agencies assume responsibility for primary control, site closures and advisories issue; (iii) research and public education by government agencies and health professionals be expanded to determine actual risks and approaches to manage them; (iv) mandatory labeling be considered for specific contaminants; (v) a better system requiring international agreements be developed in order to minimize the differences among various national regulatory approaches.

Animals↗