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Biomedical subjects

L F Mazzuckelli

Publications and source records attributed to L F Mazzuckelli.

6 recordsLinked to original sources
PubMed1991

Validation of biological markers for quantitative risk assessment.

The evaluation of biological markers is recognized as necessary to the future of toxicology, epidemiology, and quantitative risk assessment. For biological markers to become widely accepted, their validity must be ascertained. This paper explores the range of considerations that compose the concept of validity as it applies to the evaluation of biological markers. Three broad categories of validity (measurement, internal study, and external) are discussed in the context of evaluating data for use in quantitative risk assessment. Particular attention is given to the importance of measurement validity in the consideration of whether to use biological markers in epidemiologic studies. The concepts developed in this presentation are applied to examples derived from the occupational environment. In the first example, measurement of bromine release as a marker of ethylene dibromide toxicity is shown to be of limited use in constructing an accurate quantitative assessment of the risk of developing cancer as a result of long-term, low-level exposure. This example is compared to data obtained from studies of ethylene oxide, in which hemoglobin alkylation is shown to be a valid marker of both exposure and effect.

Biomarkers↗
PubMed1989

Occupational safety and health standards.

If we are to approach developing a safe and healthful workplace in a more timely fashion, a more generic approach must be considered and applied instead of developing recommendations and standards simply on a substance-by-substance basis, an approach that has been the most prominent. Some examples in which developing generic standards may be appropriate are: cholinesterase-inhibiting substances, neurotoxic agents, reproductive hazards, cold environments, and vibration syndrome, to name but a few. It is important to recognize that developing standards based on individual substances often does not allow for the role of synergism, a reaction that has had little study, but it is important in controlling occupational disease and injury. These concerns can be addressed in several ways. One is to look at processes or conditions found in the workplace; for example, coke oven emissions that OSHA has promulgated into a standard and, as NIOSH has done in their recommendations to OSHA for foundries, coal tar products, the manufacture of paint and allied coatings, field sanitation, hazardous waste management, hot environments, and confined spaces. Another is to address groups of similar substances such as NIOSH has done with alkanes, benzidine-based dyes, diisocyanates, dinitrotoluenes, and glycol ethers. A third comprehensive approach is to look at general categories of hazards, such as the generic carcinogen policy, and the hazard communication rule. Finally, risk must be considered in the development of any standard. Nelson Rockefeller once said in relation to an incidence involving a radiation hazard that, "you can't have a riskless society." I would amend this to say that you cannot have a reckless society either. Safety and health regulations are essential and must be designed, promulgated, and then enforced so that a reckless society is avoided or controlled, with a riskless society being the ultimate aim.

Humans↗
PubMed1984

Ethylene oxide: an overview of toxicologic and epidemiologic research.

Ethylene oxide (EtO) is a reactive epoxide and potent biocide. It is used widely in gas sterilization of hospital equipment. An estimated 75,000 health care workers in the United States have potential exposure. EtO binds covalently to deoxyribonucleic acid (DNA) and has been shown in 13 species to cause point mutations. Apparently, as a consequence of its alkylating ability, EtO exposure can result in chromosomal damage. In monkeys EtO exposure produces increased frequencies of sister chromatid exchanges (SCEs) and chromosomal aberrations. In man, five cytogenetic studies have shown dose-related increased frequencies of either SCE or chromosomal aberrations; in one study SCEs developed after regular exposures lasting less than five minutes per day. EtO is a reproductive toxin. In adult male rats, exposure produces decreased fertility, increased fetal deaths, and heritable chromosomal translocations. In pregnant female rats and rabbits, exposure causes increased fetal losses, and in one study in pregnant mice exposure was associated with increased numbers of malformed fetuses. In male monkeys EtO causes dose-related reductions in sperm count and sperm motility. In pregnant women, one study suggests that brief occupational exposure twice daily in concentrations of 20 ppm or above was associated with increased spontaneous abortions. EtO is carcinogenic to animals. In rats it causes dose-related increases in mononuclear cell leukemias, peritoneal mesotheliomas, and cerebral gliomas. In man, exposure has been associated in two epidemiologic studies with increased leukemias: 3 leukemias observed versus 0.2 expected in one study, and 2 observed versus 0.14 expected in the other; two additional small studies of limited power found no excess leukemias. Quantitative risk assessment indicates that from 634 to 1,093 excess deaths from cancer will occur per 10,000 workers exposed to EtO at 50 ppm over a working lifetime, and that 12 to 23 excess cancer deaths will occur per 10,000 workers exposed at 1 ppm. The National Institute for Occupational Safety and Health (NIOSH) recommends that EtO be regarded as a potential human carcinogen. NIOSH has recommended that eight-hour time-weighted average exposure to EtO be less than 0.1 ppm and that short-term peak exposure not exceed 5 ppm for more than ten minutes per working day.

Abnormalities, Drug-Induced↗
PubMed1975

The significance of circulating glycerol as a precursor of pulmonary phosphatidylcholine in the developing mammalian lung.

There is scant information regarding the contribution made by circulating precursors to pulmonary phosphatidylcholine synthesis in the developing mammalian lung. In situ pulmonary artery perfusions were performed in term New Zealand newborn rabbits with physiologic buffer containing either 3.6 mM or 10.8 mM glycerol. There was a twofold increase in nanomoles of glycerol-phosphatidylcholine synthesized at 30 min when the higher concentration of glycerol was used. Continuing with the higher concentration, a near three-fold increase was observed between the 30-min and 60-min perfusions. This data indicates that the de novo synthesis of pulmonary phosphatidylcholine is influenced by the concentration of glycerol in the perfusate as well as the duration of perfusion.

Animals↗