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Biomedical subjects

L R Glass

Publications and source records attributed to L R Glass.

8 recordsLinked to original sources

Atypical urinary opiate excretion pattern.

Heroin is rapidly metabolized in humans to 6-acetylmorphine (6-AM), which is further metabolized to morphine and morphine conjugates. Urinary 6-AM is the best diagnostic indicator of heroin abuse. This metabolite however, is usually present in urine at less than 3% of the concentration of urinary total morphine (MOR). We present two case studies of 43-year-old, apparently identical, male twins who displayed an atypical pattern of opiate metabolism. The subjects had a history of opiate abuse, and they are currently in a substance-abuse treatment program. Urine specimens submitted by these subjects for periodic clinical urine drug testing occasionally gave positive responses for opiates by enzyme immunoassay. These samples were then submitted for confirmation analysis using a mixed-mode solid-phase extraction sample preparation, trimethylsilyl derivatization, and capillary gas chromatography-electron impact-mass spectrometry confirmation analysis. These specimens contained as much as 2000 ng/mL of 6-AM with less than 350 ng/mL of MOR, which yielded 6-AM/MOR ratios as large as 1100%. Additional urine samples from these subjects that screened negative for opiates were also tested for the presence of 6-AM. Clinically significant concentrations of 6-AM were found in some of these samples.

Adult↗

The in vivo biological activity of ceramic fibres.

The well-known health effects following exposure to amphibole asbestos have led to some concern about the potential for other fibrous materials to cause similar diseases. This paper presents a summary of some of the inhalation experiments conducted with ceramic fibres in both rats and hamsters at the Research and Consulting Company, Geneva. One ceramic fibre (designated RCF1) was tested in rats at four exposure levels, this fibre was also tested in hamsters. Three other fibres were only tested in rats at the highest level--30 mg m-3. The increased incidence of tumours in these experiments has been contrasted with the negative results obtained with glass or mineral wools. However, there is evidence that the ceramic fibres were longer than the glass fibres and that long ceramic fibres were retained in lung tissue to a greater extent. This is sufficient to explain the results without recourse to explanations based on chemical differences between fibres.

Aerosols↗

Health effects of refractory ceramic fibres: scientific issues and policy considerations.

OBJECTIVES: To review the scientific literature on the health effects of refractory ceramic fibres (RCFs). The adverse effects of exposure to asbestos has led to concern about the potential for other fibrous materials to cause diseases. For this reason the human populations most heavily exposed to synthetic mineral fibres have been examined for any adverse effects and many types of fibre have been studied in animal experiments. One type of man made vitreous fibres (MMVFs), refractory ceramic fibres (RCFs), are principally used in thermal insulation at high temperatures--up to 1400 degrees C. As manufactured RCFs exist in a glassy, non-crystalline (sometimes called amorphous) state, they have various compositions, physical properties, and sized fibres. METHODS: All reports on the health effects of RCFs available up to the end of 1994 have been examined and the scientific literature reviewed although all publications have not necessarily been referenced. CONCLUSIONS: In recent inhalation experiments conducted with both rats and hamsters at the Research and Consulting Company, Geneva, at the highest dose tested (30 mg/m3) there was an increased incidence of tumours in both species. Lower doses were only examined in the rat and at these doses there was no significant excess of lung tumours. Epidemiological investigations of workers engaged in the manufacture of ceramic fibres have shown a small excess of pleural plaques. This phenomenon is being further investigated but could be due to confounding exposures. The populations available for study are small and their exposures fairly short, but it is considered prudent that they should remain under surveillance for some time to come. This is despite the fact that present exposures in the ceramic fibre industry are low (< 1 f/ml) and are being reduced.

Adenocarcinoma↗

Clearance of refractory ceramic fibers (RCF) from the rat lung: development of a model.

Chronic exposure and postexposure experiments have been recently performed in rats to evaluate the biological responses of inhaled refractory ceramic fibers (RCF) at different concentration levels. The lung burden data in the accessory lobe of the rat lung were collected during and after different exposure and postexposure periods. The size distribution of retained fibers in the lung at different time points was also measured. We used these data to develop a mathematical model of fiber clearance from the rat lung. It was found that the clearance rate did not depend significantly upon fiber size but there was a clear dependence on lung burden. As lung burden increased, the clearance rate was found to decrease. An empirical equation was derived for the clearance rate as a function of lung burden. At low burdens, rats had a retention half-time of about 126 days for RCF compared to a typical half-time of about 60 days for insoluble nonfibrous particles.

Animals↗

Chronic inhalation and biopersistence of refractory ceramic fiber in rats and hamsters.

Lifetime "nose-only" inhalation studies were conducted in rats using four types of refractory ceramic fibers (FCF), 1 micron in diameter x 22 to 26 microns length: High Purity, Kaolin, Zirconia, and After-Service; and on hamsters using Kaolin RCF. For comparison, animals also were exposed to chrysotile fibers. Rats were exposed 6 hr/day, 5 days/week for 24 months to concentrations ranging between 3 and 30 mg/m3. Time- and dose-dependent lesions in the rat included the development of interstitial fibrosis, pleural fibrosis, pulmonary tumors, and mesothelioma. Exposure to 3, 9 or 16 mg/m3 produced no excess lung tumors; no fibrosis was seen at 3 mg/m3. A significant increase in lung tumors and interstitial fibrosis was observed at 30 mg/m3. A single mesothelioma was observed in rats exposed to 9 mg/m3, while two occurred at 30 mg/m3. Hamsters were similarly exposed to 30 mg/m3 Kaolin RCF for 18 months; no lung tumors were induced, but pulmonary and pleural fibrosis were observed and there was a 42% incidence of mesothelioma. Multiple interim sacrifices together with recovery animals allowed detailed assessment of the lung burden of RCF, which was found to be dose related and, at the high doses, exceeded 10(5) fibers/mg of dry lung. During the various recovery periods there was a clear reduction in fiber burden. Mathematical modeling of these data for deposition, clearance, and retention and for species is currently underway.

Administration, Inhalation↗

Ranking of carcinogenic potency using a relative potency approach.

Protocols for long-term carcinogen bioassays have become highly refined. The ability to interpret these bioassay results beyond the experimental setting, however, has not improved commensurately. As a consequence, society is still faced with the fact that data derived in these bioassays reflect highly specific experimental conditions which are vastly different from environmental exposures of the freely roaming, outbred human. The scientific community has responded with a "collective wisdom" approach by using expert committees to interpret bioassay evidence. This committee approach is believed to be successful in protecting human health, but the list of suspected carcinogens is growing faster than the expert committees can respond. We have developed a relative potency framework for ranking the hazards represented by potential human carcinogens. The results demonstrate a rank ordering of a variety of compounds which is independent of the reference compound used to standardize the information. The philosophic basis of the approach may facilitate expert risk assessment systems development because it: (1) complements and supports "expert committee" data selection; (2) has a simple set of rules and does not require mathematical modeling; (3) requires no special situation judgments; and (4) is suitable for use with electronic data bases.

Animals↗

Genotoxic evaluation of the offgassing products of particle board.

It has been recognized that people are spending more time indoors and that pollutants are being found in elevated concentrations in this environment. Because the constituents of indoor air pollution can vary relative to a large number of factors, the nature of the indoor environment is extremely difficult to study. Of the materials used in construction of buildings which can elute complex mixtures of organic compounds, products such as particle board, plywood and insulation are known to release formaldehyde into the indoor environment. We have employed a modification of the Ames Salmonella/microsome assay with both DNA repair-proficient and -deficient strains and determined that one such material, particle board, emitted mutagenic and genotoxic substances. The materials offgassing from the particle board demonstrated a dose-related response in both mutagenicity and toxicity. It was also observed that incubation at 37 degrees C produced a decrease in both endpoints which was related to time of incubation. In addition, detectable amounts of twelve other organic compounds were identified as offgassing from the incubated particle board.

Animals↗