Biomedical subjects
Publications and source records attributed to C Kirwin.
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The carcinogenic and chronic toxicity potential of commercial hexane solvent was evaluated in F-344 rats and B6C3F1 mice (50/sex/concentration/species) exposed by inhalation for 6 h/day, 5 days/week for 2 years. Target hexane vapor concentrations were 0, 900, 3000, and 9000 ppm. There were no significant differences in survivorship between control and hexane-exposed groups, and clinical observations were generally unremarkable. Small, but statistically significant decreases in body weight gain were seen in rats of both sexes in the mid- and high-exposure groups and in high-expsoure female mice. The only noteworthy histopathological finding in rats was epithelial cell hyperplasia in the nasoturbinates and larynx of exposed groups. This response was judged to be indicative of upper respiratory tract tissue irritation. No significant differences in tumor incidence between control and hexane-exposed rats were found. In mice, uterine tissue from the high-exposure females exhibited a significant decrease in the severity of cystic endometrial hyperplasia compared to controls. An increase in the combined incidence of hepatocellular adenomas and carcinomas was observed in high-exposure female mice. The incidence of liver tumors was not increased in the mid- or low-exposure female mice or in male mice exposed to hexane. An increased incidence of pituitary adenomas was observed in female, but not male mice. This finding was not believed to have been treatment-related because the incidence in the control group was unusually low, and the incidence in exposed groups was not dose-related and was within the historical control range. No other neoplastic changes judged to be treatment-related were observed in tissues from male or female mice. In conclusion, chronic exposure to commercial hexane solvent at concentrations up to 9000 ppm was not carcinogenic to F-344 rats or to male B6C3F1 mice, but did result in an increased incidence of liver tumors in female mice.
A series of acute inhalation exposures was performed with airborne hydrogen fluoride (HF) to establish the concentration response for nonlethal effects in the rat. Exposures were either 2 or 10 min long; concentrations ranged from 135 to 8621 ppm. Three additional exposures (20 to 48 ppm) were performed for 60 min. A mouth-breathing (MB) model with a tracheal cannula was used in most of the exposures to maximize delivery of the HF to the lower respiratory tract. Endpoints on the day after exposure included hematology, serum chemistry, bronchoalveolar lavage, pulmonary function, organ weights, and histopathology. Nasal resistance was measured in nose-breathing (NB) groups. Effects of exposure were generally limited to the respiratory tract and included alveolitis, bronchial lesions, altered parameters of pulmonary function and bronchoalveolar lavage, and mucosal necrosis, inflammation, and fibrinopurulent exudate in airways. Observed changes were concentration related and appeared more pronounced in major airways near the point of entry (trachea in MB animals and nose in NB animals). One group of MB animals exposed for 10 min to 1454 ppm was evaluated at 3 and 14 wk after exposure; the acute effects had resolved by those times. The effects of 2-min exposures were consistently more severe than those from 10-min exposures to the same product of concentration x time. Exposures of MB animals for 60 min to 20 or 48 ppm HF did not result in observable adverse effects, although quasistatic pressure-volume curves were shifted upward slightly after 48 ppm. These data provide an integrated picture of the concentration-related effects of short nonlethal exposures to HF.
A series of acute inhalation exposures of female rats was conducted with hydrogen fluoride (HF) to establish a concentration-response curve for nonlethal exposures. Durations of 2 and 10 min were used to simulate possible short-term exposures. Concentrations of HF ranged from 593 to 8621 ppm for 2-min exposures and from 135 to 1764 ppm for 10-min exposures. Additional exposures were performed for 60 min at 20 and 48 ppm HF for comparison to existing Emergency Response Planning Guidelines. Animals were evaluated on the day after exposure for changes in parameters of bronchoalveolar lavage, pulmonary function, hematology, serum chemistry, body weight, organ weights, and histopathology. Most exposures were performed with orally cannulated animals to bypass absorption of HF in the nose and achieve maximum delivery of HF to the lower airways. One of the primary uses of the resulting data was to estimate a concentration to which most people could be exposed for 10 min without severe of irreversible health effects. This level was 130 ppm. It was predicted that irritation would occur at this concentration, but the effects on t he respiratory tract would not be "serious" and would be expected to be reversible. The results of this experiment and the subsequent analysis of the data provide an important aid in he planning of responses to an accidental release of HF.
Hydrofluoric acid (HF) burns are characterized by progressive tissue necrosis and severe pain. Numerous topical treatments have been proposed, yet few have been studied experimentally. The present study was designed to examine the comparative efficacy of recommended treatments. Hair on the hind legs of rats was removed and 48 hours later 70% HF was applied. Calcium gluconate, Zephiran (benzalkonium chloride), A + D Ointment, aloe gel, and magnesium ointment were applied topically and burn development was monitored. Calcium gluconate significantly reduced burn size as early as one hour after application. Significant protection continued for seven days after the single application. The other treatments were not effective in decreasing or delaying HF burn development. The results indicated that calcium gluconate ointment was the most effective topical treatment for HF burns.
The reproductive effects of inhalation exposure to commercial hexane vapors were evaluated in Sprague-Dawley rats. Males and females were exposed to commercial hexane vapor at target concentrations of 0, 900, 3000 or 9000 ppm for 6 h a day, 5 or 7 days a week, over two generations. In addition to pre-breed exposures of 10 weeks' duration, exposures continued through mating, gestation and lactation. At both the F0 breed to produce F1 litters and the F1 breed to produce F2 litters, reproductive parameters were unaffected by commercial hexane exposure. The mating, fertility and gestational indices, as well as litter size and postnatal survival, were not significantly different between exposure groups. However, reductions in body weight and body weight gain were observed in both F1 and F2 litters exposed to 9000 ppm. Effects on body weight were not observed in offspring exposed to the two lower concentrations of commercial hexane. Histopathological examination of selected tissues revealed hyaline droplet nephropathy in adult F0 and F1 males exposed to 9000 ppm. This finding was anticipated and is not believed to be relevant for the assessment of human health effects. No other treatment-related histopathological lesions were observed. Thus, exposure of rats to commercial hexane for two generations resulted in reduced body weight gains at 9000 ppm but no adverse effects on reproduction. These findings suggest that occupational exposure to commercial hexane vapors at currently recommended threshold limit value concentrations (i.e. TLV for n-hexane is 50 ppm and TLV for other hexane isomers is 500 ppm) should not pose a reproductive hazard.