Methyl tertiary butyl ether inhalation in rats: a single generation reproduction study.

Male rats exposed to target concentrations of methyl tertiary butyl ether (MtBE) at 300, 1300 and 3400 ppm for 6 hours/day, 5 days/week for 12 weeks were mated to female rats exposed to the same concentrations for a 3-week period. Exposures continued through the mating period and the females continued exposures during gestation and from days 5-21 lactation of the litters (F1a) (no exposures days 0-4 lactation). A second litter (F1b) was produced under the same mating and post mating exposure regimen. No adverse effect of treatment was observed with the adult animals (Fo) throughout the in-life portion of the study. The only remarkable finding was an increased incidence of dilated renal pelves in the low- and high-dose females (Fo). All gonad weights, male accessory reproductive organ weights, organ-to-body weight ratios and reproductive organ histopathology were unremarkable upon comparison of treated animals with air sham controls. The mating indices and fertility indices in exposed animals for both mating intervals (F1a and F1b) were not significantly different from controls. Pregnancy rates were comparable between treated and control females for the first litter interval (F1a) but were slightly lower (not statistically significant) than control on the second litter interval (F1b). Treated animal mean gestation length and the mean number of pups at birth were not statistically different from controls. The pup viability indices at birth were comparable for control and treated groups for the F1a generation, but the mid- and high-dose groups displayed a slight statistically significant decrease in the F1b generation; the decrease was not considered to be biologically significant and perhaps not treatment-related. Litter survival indices were comparable between control and treated groups for both litter intervals. Pups of mid- and high-dose females had slightly lower (not statistically significant) mean weights at days 14 and 21 of lactation but this was not considered treatment-related. The most frequent post-mortem observation for pups sacrificed at day 21 of lactation was dilated renal pelves. This did not appear to be related to treatment. It is concluded that MtBE inhalation in rats results in little adverse reproductive toxicity as shown in a two litter, one generation reproduction assay in rats.

Two-year inhalation toxicity study of petroleum coke in rats and monkeys.

Sprague-Dawley rats and Cynomolgus monkeys were exposed to dust aerosol concentrations (0, 10.2, and 30.7 mg/m3) of micronized delayed process petroleum coke for 6 hr/day, 5 days/week over 2 years. With the exception of pulmonary effects, particularly in the rats, no significant adverse treatment-related effects were observed. Both dust-exposed groups of both species exhibited a gray to black discoloration of the lung, an observation consistent with pulmonary deposition of the coke dust, as well as increased absolute and/or relative lung weight values. The pulmonary histopathology in the monkeys was limited to the deposition and phagocytosis of the test material by pulmonary macrophages. The rats also exhibited these responses, but with concomitant signs of chronic inflammation and focal areas of fibrosis, bronchiolization, sclerosis, squamous alveolar metaplasia, and keratin cyst formation. No difference in the mortality rate was observed between the control and exposed groups of rats. Lastly, no significant increases in chromosomal aberrations were observed in rodents of the 10.2 or 30.7 mg/m3 exposure groups when examined after 5 days, 12 months, and 22 months of exposure.

Absence of hydrocarbon-induced nephropathy in rats exposed subchronically to volatile hydrocarbon mixtures pertinent to gasoline.

Ninety-day inhalation studies were conducted on 50:50 weight percent (wt %) mixtures of n-butane:n-pentane and isobutane:isopentane, respectively, and on a distillation cut boiling below 145 degrees F of a reference unleaded gasoline blend to assess the nephrotoxicity of these volatile mixtures. The mixtures of butanes and pentanes were selected because these four hydrocarbons are the most prevalent components of gasoline vapors encountered under typical occupational exposures. The 0-145 degrees F gasoline distillation fraction was tested because it reasonably approximates the composition of gasoline vapors measured under occupational settings. Male and female F-344 rats were exposed to 2 levels of each mixture, 6 hours per day, 5 days per week, for 13 weeks. The target concentrations for the butane:pentane mixtures were 4500 and 1000 parts per million (ppm), while 5200 and 1200 ppm were set for the gasoline distillation fraction. An interim sacrifice was conducted after 28 days. The rats were not significantly affected by the exposures, and there was no evidence of hydrocarbon-induced nephropathy in either sex at the termination of each study. However, at the 28-day interim sacrifice period for both butane:pentane mixtures, mild, transient treatment-related but not exposure-related kidney effects were observed in the male rats. These perturbations were absent at the interim sacrifice period for the gasoline distillation fraction.

Hydrocarbon nephropathy in male rats: identification of the nephrotoxic components of unleaded gasoline.

Previous subchronic and/or chronic inhalation studies of unleaded gasoline and a variety of petroleum naphthas, solvents, and distillates have shown that these complex materials are capable of inducing a distinctive nephropathy which appears limited to male rats. Therefore a series of gavage screening studies using male F-344 rats was conducted on components of gasoline to more clearly identify the major contributors to this nephrotoxicity. The dosing regimen consisted of 20 doses administered once daily, 5 days per wk for 4 wk. Tested were 15 pure hydrocarbon compounds typically found in unleaded gasoline boiling range, 4 naphtha streams representative of those commonly used to blend gasolines and 3 distillation fractions covering the less volatile portions of gasoline. The results revealed that the alkane (paraffin) components were primarily responsible for the nephrotoxic activity seen in unleaded gasoline, with a positive structure-activity response relating the degree of alkane branching to the potency of the nephrotoxic response. In addition, the nephrotoxic activity observed with the naphtha streams and distillation fraction correlated well with the proportion of branched alkanes contained in each.

Toxicological characteristics of refinery streams used to manufacture lubricating oils.

In the past, reports on the tumorigenic potential of lubricating oils in experimental animals have poorly defined the materials under study. In this paper the results of mouse skin painting studies with 46 clearly defined samples of refinery streams associated with lubricating oil processing show that modern conventional solvent refining of distillates removes tumorigenic potential while conventional acid refining may not. Furthermore, dewaxing, hydrofinishing, and clay treatments do not appear to mitigate the tumorigenicity of the lubricant distillates. Lubricant processing has changed over the years and assessments of the carcinogenicity of present-day lubricating materials must be based on knowledge of modern processing.