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Biomedical subjects

S M Rappaport

Publications and source records attributed to S M Rappaport.

At least 91 records · Page 5Linked to original sources

Detection of styrene oxide-DNA adducts in lymphocytes of a worker exposed to styrene.

The 32P-postlabelling procedure has been used to detect styrene oxide (SO)-DNA adducts. Reactions of SO with DNA and dGMP in vitro produced adducts that were similar, indicating that dGMP was the primary base for modification in DNA. Two SO adducts were also detected in DNA isolated from lymphocytes of a styrene-exposed worker but not in DNA from an unexposed worker. These results indicate that 32P-postlabelling can be used for quantification of DNA adducts in workers exposed to styrene.

DNA↗

A method for evaluating the mean exposure from a lognormal distribution.

OSHA's risk assessments, made in support of new standards, implicitly assume that workers are exposed at the level of the PEL on the average over their working lifetimes. This approach seems to be justified at least in cases where the toxicant is eliminated slowly from the critical site in the body. Thus, there are situations where the industrial hygienist should seek to evaluate worker mean exposure overtime. A simple testing procedure is proposed for determining whether the mean exposure of a lognormally-distributed exposure series, mu c, is less than the Permissible Exposure Limit (PEL) at desired levels of significance and power. With the assumption that the exposures are described adequately by a longnormal distribution, the method allows realistic exposure scenarios where mu c less than PEL to be declared acceptable with between two and fifty 8-hr TWA measurements, depending upon the value of muc and the level of variability. Application of the methods to three industrial data sets indicates that the approach is viable.

Air Pollutants, Occupational↗

The rules of the game: an analysis of OSHA's enforcement strategy.

Although OSHA promulgates standards for chemical exposures on the basis of workers' relative risk of acquiring chronic disease, it interprets the limits as absolute levels never to be exceeded. This poses a dilemma to the gathering of useful information which can be used to assess and reduce exposures, because employers can maximize compliance outcomes by minimizing exposure monitoring. The result is that, in the absence of adequate information, the working population's true risk of acquiring disease is essentially unknown and average exposures of several times the permissible exposure limit (PEL) can be declared in compliance. The dilemma could be resolved if OSHA would define compliance in terms of one or more parameters of the cumulative exposure distribution. Since OSHA's current method of assessing risks is based upon average exposures, enforcement of the PEL as the limit of each worker's true mean exposure would be internally consistent. This change could have the effect of encouraging employers to monitor exposures since the confidence interval surrounding the mean can be narrowed with increased sample size.

Humans↗

Conversion of 1-naphthol to naphthoquinone metabolites by rat liver microsomes: demonstration by high-performance liquid chromatography with reductive electrochemical detection.

1-Naphthol has recently been shown to be selectively toxic to short-term organ cultures of human colorectal tumor tissue. The mechanism underlying 1-naphthol's selective toxicity is as yet unknown, but may be due to the formation of naphthoquinone metabolites, which are known to be highly toxic to tumor cells. By using high-performance liquid chromatography with reductive electrochemical detection, it has been possible to show that 1-naphthol is converted to naphthoquinone metabolites by rat liver microsomes. At least two metabolic pathways, independent of cytochrome P-450, appear to be involved. Iron-dependent lipid peroxidation appears to be responsible for at least part of the conversion of 1-naphthol to predominantly 1,4-naphthoquinone, and it seems likely that superoxide anion radical generation by NADPH-cytochrome P-450 reductase could also catalyze this conversion. 1-Naphthol therefore seems to be converted to cytotoxic naphthoquinone metabolites by mechanism(s) dependent upon the generation of free radicals in rat liver microsomes. The results also demonstrate the utility of HPLC with reductive electrochemical detection for investigations of quinone metabolite formation and the measurement of quinones of both physiological and environmental interest.

Animals↗

Industrial hygiene data: compliance, dosage and clinical relevance.

Much of the data collected by industrial hygienists on levels of airborne contaminants in the workplace is of marginal relevance to the needs and interests of physicians practicing occupational medicine. Several factors influence data collection. Regulatory agencies require rigid interpretation of exposure levels, yet concentrations of contaminants in the air environment vary considerably. This discrepancy suggests a different approach to dealing with the regulatory problem, one which recognizes its inherent statistical nature. Increased attention also should be devoted to basing sampling intervals more directly on toxicological measurements. These changes would result in the collection of environmental data of greater relevance to physicians, toxicologists and epidemiologists because such information would allow more realistic estimates of the hazard of a cumulative exposure for a given work population.

Air Pollutants↗

Identification of 2-nitrofluorene in diesel exhaust particulates.

Diesel exhaust particulates contain mutagens which are direct-acting in the Ames test. A dichloromethane extract of these particulates was separated by liquid chromatography and analyzed by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). 2-Nitrofluorene, a known carcinogen and direct mutagen, was positively identified by comaxima of ion fragments and retention time on the gas chromatograph.

Air Pollutants↗

Air sampling in the assessment of continuous exposures to acutely-toxic chemicals. Part I--Strategy.

This paper describes the conceptual basis for assessing the hazard of continuous exposures to acutely toxic chemicals. It is stressed that the variability of workers' short-term exposures to airborne chemicals must be considered in establishing strategic criteria which define an acceptable (or unacceptable) environment. The argument is developed that the traditional strategy of an absolute ceiling limit is unworkable since any set of exposures can be declared out of compliance if a sufficiently large number of samples is collected. It is proposed that acute-exposure limits be defined instead as air concentrations that can be exceeded by an explicit fraction of the population of exposures. An "exceedance" rate of 5% is suggested provided that exposure limits incorporate appropriate safety factors which are relatively large for potent acute toxins and small for irritants. The implications of this strategy are analyzed with some existing ceiling limits proposed by NIOSH.

Air Pollutants↗

Volatilization of mutagens from beef during cooking.

The process of cooking beef substances which are mutagenic in the Ames Salmonella/microsome bioassay [1,2]. In this study, the formation and disposition of basic mutagens produced by cooking beef at different temperatures were examined. Mutagenic activity increased exponentially with cooking temperature between 137 degrees C and 252 degrees C. However, the amount of mutagenic activity remaining in the meat was only 1--7% of that which was volatilized into the air. The ingested dose of mutagens may therefore be significantly influenced by factors which restrict the dissipation of mutagens from the container, as well as by cooking temperature. Inhalation of airborne mutagens from cooking, as an alternative route of exposure, should be investigated when considered in light of some epidemiological data showing an excess of lung and bladder cancer among cooks and kitchen workers.

Animals↗

Air sampling and analytical procedures for benzidine, 3,3'-dichlorobenzidine and their salts.

The purpose of the study was the development of new air-sampling and analytical procedures for benzidine, 3,3'-dichlorobenzidine and their salts. Air is drawn through a glass-fiber filter followed by a bed of silica gel to collect these substances as either particles or vapors. The compounds are extracted from the sampler and analyzed by HPLC with sensitivities in the range of 3 micrograms/m3 for 48-L air samples. The methods were evaluated in the laboratory with test aerosol atomospheres and found to be unaffected by temperature or humidity of the sampled environment. Tests of precision, sample stability and separation from interferants indicate that the method should provide reliable results for personal monitoring procedures.

Air↗

Direct-acting mutagens in automobile exhaust.

Particulate matter in city air contains chemicals which are mutagenic in the Ames Salmonella typhimurium assay. In residential urban areas, the principal mutagens in air do not require liver enzymes to be activated. The source of these liver independent (direct-acting) mutagens may be automobile exhaust because (1) the mutagenic activities were correlated to the lead content or air, (2) the mutagens were found exhaust samples from automobiles and from an experimental CFR single-cylinder gasoline engine, and (3) these mutagens were not found in fuel or unused motor oil, but were found in used motor oil. The strain specificity and the fact that liver enzymes were not required for activation indicated that the exhaust and airborne mutagens were not unsubstituted polycyclic aromatic hydrocarbons (PAH), aromatic amines, alkylnitrosamines or aliphatic epoxides, peroxides and hydroepoxides. A number of nitro-substituted aromatic compounds are direct-acting mutagens in the Ames test, and it is possible that nitration of PAH in exhaust may form the compounds observed here. We synthesized 6-nitrobenzo [a] pyrene and found it to be a potent, direct-acting mutagen with activity comparable to that of benzo-[a] pyrene.

Animals↗

The generation of aerosols of carcinogenic aromatic amines.

A system for producing test atmospheres of carcinogenic aromatic amines is discussed. The aerosol generator, a specially disigned compressed-gas nebulizer, operated at a temperature above each compound's melting point utlizing nitrogen as the driving force. The nebulizer output and size distributions of aerosols of 4,4'-methylenebis(2-chloroaniline) (MOCA), benzidine, and 3,3'-dichlorobenzidine are given.

3,3'-Dichlorobenzidine↗

Air sampling and analysis in a rubber vulcanization area.

Results of sampling and analysis of air in a rubber vulcanization area are described. Organic compounds were collected on activated charcoal, desorbed with carbon disulfide and analyzed by gas chromatography. Several previously identified substances were quantitated, including styrene, toluene, ethylbenzene, and several oligomers of 1,3-butadiene. Concentrations ranged from 0.007 to 1.1 ppm.

Air Pollutants↗

The interpretation and applicati-n of OSHA carcinogen standards for laboratory operations.

A safety protocol implemented at the Los Alamos Scientific Laboratory for a project involving 14 chemical carcinogens is described. Specific topics pertaining to facilities, personnel practice, laboratory operations, decontamination and disposal are discussed within the context of regulations issued by the Occupational Safety and Health Administration.

Accident Prevention↗