Occupational exposure to asbestos in the steel industry (1972-2006).

BACKGROUND: Historically, the use of asbestos in steelmaking has been limited to a few applications. Due to its physical and chemical properties, asbestos was not necessary or suitable for most purposes in a steel mill. The few applications where asbestos were used (i.e., certain gaskets, brakes, protective cloth, refractory materials, insulation materials, and hot top products) were replaced by alternative materials as they became available. OBJECTIVE: We discuss historical uses of asbestos in steel manufacturing and the associated airborne asbestos concentrations collected at sixteen U. S. Steel facilities between 1972 and 2006. METHODS: A total of 495 personal airborne asbestos samples from the U. S. Steel industrial hygiene records were analyzed across four time periods corresponding to changes in the OSHA permissible exposure limit (PEL) for asbestos. 68% of the samples (n = 337) were considered representative of an employee's workday. The remaining samples (n = 158) represented task samples. Samples were grouped by facility, department, and job category within the four time periods. RESULTS: The average fiber concentrations measured for each facility and department over time were below the contemporaneous OSHA PEL. The mean representative workday asbestos air concentration from 1972 and 1975 was 1.09 f/cc. The mean representative workday concentration decreased to 0.13 f/cc between 1976 and 1985, then decreased again to 0.02 f/cc between 1986 and 1993 and 0.03 f/cc between 1994 and 2006. For task samples, the mean air concentration from 1972 to 1975 was 3.29 f/cc. The mean task sample concentration decreased to 0.48 f/cc between 1976 and 1985, then decreased again to 0.01 f/cc between 1986 and 1993 and 0.03 f/cc between 1994 and 2006. Only eleven out of the 495 samples (2.2%), for both task and representative workday samples, were in exceedance of the contemporaneous PEL(as an 8-hour TWA), ten of which occurred prior to 1978. Eight of these eleven PEL exceeding samples were task samples. Of the remaining three representative workday samples, two had unknown sampling times. IMPACT: This paper presents an analysis of all the available personal sampling data for airborne asbestos across 16 facilities of the U. S. Steel Corporation between 1972 and 2006. This dataset has previously never been publicly shared or analyzed. It represents one of the more complete industrial hygiene datasets from a corporation to be presented in a scientific journal and, due to the similarities in the processes at each mill, it should reflect analogous exposures throughout the steelmaking industry in the United States. One of the benefits of presenting these data is that it also provides insight into where asbestos-containing materials (ACMs) were used in the steel making process. This is just one example of a large firm that released information that had previously remained in file cabinets for decades. We believe that another benefit of publishing this paper is that it may encourage the largest firms in industry to assemble and analyze their industrial hygiene data to benefit the occupational hygiene, medical, and epidemiology communities. This can support future epidemiology studies and improve the design of future industrial hygiene programs.

A critical review of the 2020 EPA risk assessment for chrysotile and its many shortcomings.

From 2018 to 2020, the United States Environmental Protection Agency (EPA) performed a risk evaluation of chrysotile asbestos to evaluate the hazards of asbestos-containing products (e.g. encapsulated products), including brakes and gaskets, allegedly currently sold in the United States. During the public review period, the EPA received more than 100 letters commenting on the proposed risk evaluation. The Science Advisory Committee on Chemicals (SACC), which peer reviewed the document, asked approximately 100 questions of the EPA that they expected to be addressed prior to publication of the final version of the risk assessment on 30 December 2020. After careful analysis, the authors of this manuscript found many significant scientific shortcomings in both the EPA's draft and final versions of the chrysotile risk evaluation. First, the EPA provided insufficient evidence regarding the current number of chrysotile-containing brakes and gaskets being sold in the United States, which influences the need for regulatory oversight. Second, the Agency did not give adequate consideration to the more than 200 air samples detailed in the published literature of auto mechanics who changed brakes in the 1970-1989 era. Third, the Agency did not consider more than 15 epidemiology studies indicating that exposures to encapsulated chrysotile asbestos in brakes and gaskets, which were generally in commerce from approximately 1950-1985, did not increase the incidence of any asbestos-related disease. Fourth, the concern about chrysotile asbestos being a mesothelioma hazard was based on populations in two facilities where mixed exposure to chrysotile and commercial amphibole asbestos (amosite and crocidolite) occurred. All 8 cases of pleural cancer and mesothelioma in the examined populations arose in facilities where amphiboles were present. It was therefore inappropriate to rely on these cohorts to predict the health risks of exposure to short fiber chrysotile, especially of those fibers filled with phenolic resins. Fifth, the suggested inhalation unit risk (IUR) for chrysotile asbestos was far too high since it was not markedly different than for amosite, despite the fact that the amphiboles are a far more potent carcinogen. Sixth, the approach to low dose modeling was not the most appropriate one in several respects, but, without question, it should have accounted for the background rate of mesothelioma in the general population. Just one month after this assessment was published, the National Academies of Science notified the EPA that the Agency's systematic review process was flawed. The result of the EPA's chrysotile asbestos risk evaluation is that society can expect dozens of years of scientifically unwarranted litigation. Due to an aging population and because some fraction of the population is naturally predisposed to mesothelioma given the presence of various genetic mutations in DNA repair mechanisms (e.g. BAP1 and others), the vast majority of mesotheliomas in the post-2035 era are expected to be spontaneous and unrelated in any way to exposure to asbestos. Due to the EPA's analysis, it is our belief that those who handled brakes and gaskets in the post-1985 era may now believe that those exposures were the cause of their mesothelioma, when a risk assessment based on the scientific weight of evidence would indicate otherwise.

Preliminary pharmacokinetics of intravenous and subcutaneous dolasetron and pharmacodynamics of subcutaneous dolasetron in healthy cats.

Objectives The objectives were to evaluate the pharmacokinetics (PK) of subcutaneous (SC) and intravenous (IV) dolasetron and the pharmacodynamics (PD) of SC dolasetron in healthy cats. Methods Five cats with unremarkable complete blood count, serum biochemistry and urinalyses were utilized. In the PK study, cats received 0.8 mg/kg SC and IV dolasetron in a crossover format. Serum samples were obtained via a jugular catheter at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36 and 48 h after the administration of dolasetron. Dolasetron and the active metabolite hydrodolasetron were measured using liquid chromatography/tandem mass spectrometry. Non-compartmental PK analysis was performed. In the PD study, SC dolasetron (0.8 mg/kg and 1.0 mg/kg) and saline were administered 30 mins prior to administration of 0.44 mg/kg intramuscular xylazine in a randomized three-way crossover. Number of emetic events, lip licks, time to onset of emesis and visual nausea score were scored by a blinded observer. Results In the PK study, dolasetron was quickly metabolized to the active metabolite hydrodolasetron, limiting assessment of dolasetron PK parameters. Median (range) PK parameters for IV hydrodolasetron were as follows: maximum serum concentration (Cmax) 116 ng/ml (69-316 ng/ml), time to maximum concentration (Tmax) 0.5 h (0.3-0.5 h), half-life 3.3 h (2.9-7.2 h) and area under the curve until the last measurable concentration (AUClast) 323 h/ng/ml (138-454 h/ng/ml). Median (range) PK parameters for SC hydrodolasetron were as follows: Cmax 67.9 ng/ml (60.4-117 ng/ml), Tmax 0.5 h (0.5-1.0 h), half-life 3.8 h (2.9-5.3 h) and AUClast 437 h/ng/ml (221.5-621.8 h/ng/ml). There was no significant difference in exposure to hydrodolasetron between the routes of administration. With regard to PD, when dolasetron was administered prior to xylazine, there was no significant difference in the mean number of emetic events, lip licks, time to onset of emesis or visual nausea score when compared with saline. Conclusions and relevance Administration of 0.8 mg/kg dolasetron does not maintain serum concentrations of active metabolite for 24 h. Administration of dolasetron at 0.8 mg/kg and 1 mg/kg did not prevent xylazine-induced vomiting. Additional feline dose studies are needed to determine if a higher dose is efficacious.