Chronic inhalation carcinogenicity study of commercial hexane solvent in F-344 rats and B6C3F1 mice.

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.

Short-term exposures of rats to airborne hydrogen fluoride.

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.

Acute effects of 10-minute exposure to hydrogen fluoride in rats and derivation of a short-term exposure limit for humans.

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.

Two-generation reproduction study on commercial hexane solvent.

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.

Cytogenetic studies on commercial hexane solvent.

Commercial hexane is a solvent mixture of six-carbon isomers, consisting principally of n-hexane, 3-methylpentane, methylcyclopentane and 2-methylpentane. The potential of commercial hexane to produce chromosome aberrations was evaluated in both an in vitro assay using Chinese hamster ovary (CHO) cells and an in vivo cytogenetics assay using Sprague-Dawley rats. The CHO cells were exposed to media containing commercial hexane at concentrations of 0.014-0.42 microliters ml-1 in the presence and absence of an S-9 activation mixture. Cellular toxicity was observed at the higher dose levels, but no increase in chromosome aberrations was observed in either the non-activated or S-9-activated systems. For the in vivo cytogenetics assay, rats were exposed nose-only for 6 h per day for 5 consecutive days to commercial hexane vapor at target concentrations of 900, 3000 and 9000 ppm. Bone marrow cells were collected at 6 and 24 h after the midpoint of the last exposure. Metaphase cells were examined microscopically for chromosome aberrations. No statistically significant increases in aberrant cells were observed in the commercial hexane-exposed animals of any dose group at either of the bone marrow harvest times. In conclusion, commercial hexane did not produce chromosomal mutations under the conditions of these studies.

Inhalation teratology studies of n-butyl mercaptan in rats and mice.

n-Butyl mercaptan (n-BM) is used as a solvent and a chemical intermediate. Pregnant Charles River CD-1 mice and COBS CD rats were randomly assigned to a control group and to three n-BM-exposed groups of 25 rats and 25 mice each. The animals were exposed by whole-body inhalation to mean n-BM concentrations of 10, 68, or 152 ppm on a 6-hr daily exposure schedule. Rats were exposed on Gestation Days 6-19 and mice on Gestation Days 6-16. The control group was exposed to filtered air only on a comparable regimen. Cesarean sections were performed on all surviving mice on Gestation Day 17 and on all rats on Gestation Day 20. Seventeen of the n-BM-treated mice died: 8 at the 68-ppm level and 9 at the 152-ppm level; none of the n-BM-treated rats died. An increased postimplantation loss and increased early resorption occurred in mice exposed at 68 and 152 ppm, indicating embryotoxicity. An increased incidence of cleft palate was observed in mice exposed to 10 or 68 ppm which was not statistically significant. Total fetal abnormalities were statistically significantly different from controls at 68 ppm where maternal lethality was observed when based on the fetal unit although not when based on the litter unit. Rats exposed to 152 ppm or less demonstrated no terata.

Comparative effectiveness of topical treatments for hydrofluoric acid burns.

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 subchronic oral toxicity of polyphenylene sulfide.

Polyphenylene sulfide was offered to Charles River CD rats for 6 months in the diet at concentrations of 0.00, 0.50, 2.75 and 5.00% (w/w). In this study, animals of both sexes consumed polyphenylene sulfide for 6 months without exhibiting compound-related effects. Parameters studied were: body weight, hematology, clinical chemistry, urinalysis, organ weights, gross pathology and histopathology.

Evaluation of the genetic activity of industrially produced carbon black.

Commercially produced oil furnace carbon black (Chemical Abstract Service Registry No. 1333-86-4) has been evaluated by five different assay for genetic activity. These were the Ames Salmonella typhimurium reverse mutation test, sister chromatid exchange test in CHO cells, mouse lymphoma test, cell transformation assay in C3H/10T1/2 cells, and assay for genetic effects in Drosophila melanogaster. Limited cellular toxicity was exhibited but no significant genetic activity was noted.