Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the Syrian golden hamster. Part II. Results of chronic exposure.

Fiberglass (FG) is the largest category of man-made mineral fibers (MMVFs). Many types of FG are manufactured for specific uses building insulation, air handling, filtration, and sound absorption. In the United States, > 95% of FG produced is for building insulation. Several inhalation studies in rodents of FG building insulation have shown no indication of pulmonary fibrosis or carcinogenic activity. However, because of increasing use and potential for widespread human exposure, a chronic toxicity/carcinogenicity inhalation study of a typical building insulation FG (MMVF 10a) was conducted in hamsters, which were shown to be highly sensitive to the induction of mesotheliomas with another MMVF. A special-application FG (MMVF 33) and amosite asbestos were used for comparative purposes. Groups of 140 weanling male Syrian golden hamsters were exposed via nose-only inhalation for 6 h/day, 5 days/wk for 78 wk to either filtered air (chamber controls) or MMVF 10a, MMVF 33, or amosite asbestos at 250-300 WHO fibers/cm(3) with two additional amosite asbestos groups at 25 and 125 WHO fibers/cm(3). They were then held unexposed for 6 wk until approximately 10-20% survival. After 13, 26, 52, and 78 wk, various pulmonary parameters and lung fiber burdens were evaluated. Groups hamsters were removed from exposure at 13 and 52 wk and were held until 78 wk (recovery groups). Initial lung deposition of long fibers (>20 microm in length) after a single 6-h exposure was similar for all 3 fibers exposed to 250-300 fibers/cm(3). MMVF 10a lungs showed inflammation (which regressed in recovery hamsters) but no pulmonary or pleural fibrosis or neoplasms. MMVF 33 induced more severe inflammation and mild interstitial and pleural fibrosis by 26 wk that progressed in severity until 52 wk, after which it plateaued. While the inflammatory lesions regressed in the recovery animals, pulmonary or pleural fibrosis did not. A single multicentric mesothelioma was observed at 32 wk. No neoplasms were found in the remainder of the study. Amosite asbestos produced dose-related inflammation and pulmonary and pleural fibrosis as early as 13 wk in all 3 exposure levels. The lesions progressed during the course of the study, and at 78 wk severe pulmonary fibrosis with large areas of consolidation was observed in the highest 2 exposure groups. Progressive pleural fibrosis with mesothelial hypertrophy and hyperplasia was present in the thoracic wall and diaphragm in most animals and increased with time in the recovery hamsters. While no pulmonary neoplasms were observed in the amosite exposed hamsters, a large number of mesotheliomas were found; 25 fibers/cm(3), 3.6%; 125 fibers/cm(3), 25.9%; and 250 fibers/cm(3), 19.5%. For the 3 fiber types, the severity of the lung and pleural lesions generally paralleled the cumulative fiber burden, especially those >20 microm length, in the lung, thoracic wall, and diaphragm. They also inversely paralleled the in vitro dissolution rates; that is, the faster the dissolution, the lower were the cumulative lung burdens and the less severe the effects.

Indoor airborne fiber levels of MMVF in residential and commercial buildings.

Man-made vitreous fibers (MMVF) have been used widely in commercial and residential buildings for over 50 years. Concerns have been expressed since the late 1960s that MMVF products may erode and contribute to fiber levels in the indoor environment. This cooperative investigation was undertaken to quantify indoor respirable fiber levels by phase contrast optical microscopy (PCOM) and to differentiate between fiber types using scanning electron microscopy with energy-dispersive X-ray microanalysis (SEM-EDX). A total of 205 stationary samples were collected using standard industrial hygiene methods in 51 residential and commercial buildings. Twenty-one simultaneous outdoor samples were collected at 19 buildings. All samples were analyzed by PCOM following the NIOSH 7400 Fiber method, "B" counting rules, and 50 randomly selected samples were analyzed by SEM-EDX. The PCOM mean value for all respirable fiber levels was 0.008 f/cc with a median value of 0.007 f/cc and a maximum value of 0.029 f/cc. Ninety-seven percent of the respirable fibers identified by SEM-EDX were determined to be organic. MMVF were detected on only two samples. Airborne fiber levels were very low and the respirable fibers present were primarily organic. The inorganic fiber levels determined by SEM-EDX which included MMVF were less than 0.0001 f/cc.

Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results.

The effects of chronic inhalation of glass fibers and amosite asbestos are currently under study in hamsters. The study includes 18 months of inhalation exposure followed by lifetime recovery. Syrian golden hamsters are exposed, nose only, for 6 hr/day, 5 day/week to size-selected test fibers: MMVF10a (Schuller 901 insulation glass); MMVF33 (Schuller 475 durable glass); amosite asbestos (three doses); or to filtered air (controls). Here we report interim results on airborne fiber characterization, lung fiber burden, and pathology (preliminary) through 12 months. Aerosolized test fibers averaged 15 to 20 microns in length and 0.5 to 1 micron in diameter. Target aerosol concentrations of World Health Organization (WHO) fibers (longer than 5 microns) were 250 fibers/cc for MMVF10a and MMVF33, and 25, 125, or 250 fibers/cc for amosite. WHO fiber lung burdens showed time-dependent and (for amosite) dose-dependent increases. After a 12-month exposure, lung burdens of fibers longer than 20 microns were greatest with amosite high and mid doses, similar for low-dose amosite and MMVF33, and smaller for MMVF10a. Biological responses of animals exposed for 12 months to MMVF10a were limited to nonspecific pulmonary inflammation. However, exposures to MMVF33 and each of three doses of amosite were associated with lung fibrosis and possible mesotheliomas (1 with MMVF33 and 2, 3, and 1 with amosite low, mid, and high doses, respectively). Pulmonary and pleural changes associated with amosite were qualitatively and quantitatively more severe than those associated with MMVF33. As of the 12-month time point, this study demonstrates that two different fiber glass compositions with similar fiber dimensions but different durabilities can have distinctly different effects on the hamster lung and pleura after inhalation exposure. (Preliminary tumor data through 18 months of exposure and 6 weeks of postexposure recovery became available as this manuscript went to press: No tumors were observed in the control or MMVF10a groups, and no additional tumors were observed in the MMVF33 group; however, a number of additional mesotheliomas were observed in the amosite groups.

Recent studies of man-made vitreous fibers. Chronic animal inhalation studies.

The history of asbestos use and asbestos-related disease is replete with comments that the public health would have been better protected if the results of laboratory investigation, epidemiologic surveys, and clinical studies were made available at appropriate intervals during the ongoing research, rather than in the generally accepted method of awaiting completion of studies prior to reporting medical and scientific findings. No substantive evidence of long-term adverse effects has been published in workers exposed to man-made vitreous fibers. Nevertheless, in an effort to preclude a repetition of this error of omission that occurred with asbestos exposure and use, the Thermal Insulation Manufacturers Association is regularly reporting interim and final data from ongoing animal studies. A significant segment of man-made vitreous fibers have now been tested in state-of-the-art chronic studies. This paper includes the recently completed animal inhalation studies on refractory ceramic fibers and fibrous glass. It also reviews interim data on mineral wool studies.

Correlation between airborne U exposure and U urinalysis results at Bear Creek Uranium.

Inhalation exposure history and U urinalysis data collected at Union Pacific Resources Company's Bear Creek Uranium milling operation, located in the Powder River Basin area of Wyoming, were studied to determine if a correlation could be made between airborne U exposure and U urinalysis results. It was observed from these data that U urinalysis results correlate with airborne U exposure levels when averaged over a period of time. The urinary U excretion rate, empirically derived from these data, was 1.8 X 10(-1) micrograms U in urine d-1 per micrograms U inhaled d-1 for samples collected after 2.9 d of no exposure.

Evaluation for compensation of asbestos-exposed individuals. II. Apportionment of risk for lung cancer and mesothelioma.

The incidence of lung cancer in the cigarette smoking population occupationally exposed to asbestos is inordinately high. A method for apportioning risk to these two agents has been developed. It utilizes degree of asbestos and smoking exposures; the time interval from onset and, where applicable, termination of both exposures; the time interval to diagnosis of lung cancer; and morphologic, physiologic, and radiological evidence of pulmonary fibrosis.

Evaluation for compensation of asbestos-exposed individuals. I. Detection and quantification of asbestos-related nonmalignant impairment.

An objective method for measuring nonmalignant respiratory impairment caused by inhaled asbestos has been devised. Three standard physiologic tests (the forced vital capacity [FVC], the forced expiratory volume in 1 s [FEV1], the single-breath diffusing capacity for carbon monoxide [DCO]) and the posteroanterior chest roentgenogram are utilized. The age-, height-, and sex-specific normal ranges of the FVC%, the DCO%, and the FEV1/FVC% have been used in the method. The theory and rationale are described. The resulting algorithm can be presented using a nomogram. Data on 586 asbestos-exposed subjects were analyzed by the proposed method. Empirical evaluation showed the sensitivity to be greater than 90% in definitive diagnosis of asbestosis without airflow obstruction, and the specificity to be greater than 80% for those cases judged eligible for nomographic evaluation. Exceptions were found in 15 cases diagnosed clinically as asbestosis, none of whom had any evidence of pulmonary fibrosis. In addition, 50 cases diagnosed as "no asbestosis" did have evidence of pulmonary fibrosis and would have qualified for some compensation by the proposed method. In summary, this approach has been shown to yield a reliable final asbestos-related lung impairment index that, when taken together with individual societal data, can provide a reliable basis for determining compensation.

Fiber counting: a source of error corrected.

Optical counting of fibers (from a filter sample of industrial air, for example) involves determining how many fibers are within counting fields which are squares of side lengths. It is correct to count all those fibers which are completely within the field and half of those which intersect only one side. It is shown here to be incorrect to count half those fibers which intersect two sides; the magnitude of this error is calculated, the calculations being verified through a Monte Carlo simulation. The fractional overcount for fibers of length L less than or equal to s is (L/s)2/2pi.

Regulation of human lipolysis. In vivo observations on the role of adrenergic receptors.

Changes in the plasma free fatty acids of a pancreatectomized subject and in free fatty acids and insulin in 10 normal subjects in response to the in vivo infusion of epinephrine alone, epinephrine plus phentolamine, and epinephrine plus propranolol indicate that both alpha and beta adrenergic receptors are present in human adipose tissue. Under the experimental conditions used, adipose tissue appeared to be more responsive to epinephrine than did the cardiovascular system.