API TR 405-1995
$20.15
An Inhalation Oncogenicity Study of Commercial Hexane in Rats and Mice
Published By | Publication Date | Number of Pages |
API | 1995 | 106 |
This study, conducted for the American Petroleum Institute, was designed to assess the oncogenic effect of commercial hexane. The test substance wa; administered by-whole-body inhalation as a vapor to Fischer 344 rats and B6C3F1 mice (50/sex/group/species). This report presents the results from the mouse portion of the study. The rat results are presented in a separate report. The test substance was administered for six hours per day, five days per week, for approximate two years at target concentrations of 900, 3000 and 9000 parts per million (ppmf of air. The 9000 ppm high exposure level was based upon the results of a 90-day sub chronic study. In addition, 9000 ppm is approximately 80%of the lower explosive limit. Exposures were initiated on 23 January 1990 and completed on 20 January 1992. Exposure levels were analyzed hourly using an infrared spectrophotometer(IR). Gas chromatographic (GC) confirmation of the commercial hexane chamber exposure levels as well as analysis for the six major components were also conducted. Particle size distribution measurements of any background aerosol were made monthly. Detailed physical examinations were conducted weekly on all animals. Ophthalmoscopes examinations were performed on all animals pretest and prior to sacrifice. Body weight measurements were recorded pretest on Test Days -12, -7 and O, weekly through Week 13, monthly through Week 101 and just prior to sacrifice. Differential white blood cell counts were analyzed pretest for all animals and at Month 12, Month 18 and prior to termination on Group I and IV survivors. Following the two years of exposure, all survivors were sacrificed. Complete macroscopic examinations were conducted for all animals. Microscopic examinations were performed in the lungs in all animals, in selected tissues in all Group I and IV animals, and in all animals which died or were sacrificed moribund prior to their scheduled sacrifice. In addition, microscopic examinations were conducted in the livers of Group II and III males and females and in the pituitaries of the Group II and III females.
The cumulative mean exposure concentrations as determined by IR were 900, 3000 and 9018 ppm. GC analyses confirmed these exposure levels and indicated commercial hexane was stable over the duration of the study with a mean composition (%) of: n-hexane (51.5), methyl cyclopentane (16.0), 3-methylpentane (16.1), 2-methylpentane (12.9), cyclohexane (3.3) and 2,4-dimethylpentane (0.17). Particle size distribution determinations indicated that no significant test substance aerosol was present in the exposure chambers.
At termination of the study, in the control group survivorship was 85% in the males and 80% in the females. There was no significant difference in survivorship among any of control or exposure groups.
Physical observations, hematological and ophthalmoscope examinations found no signs of any commercial hexane related effects.
Mean body weights and body weight gains in the exposed animals were not statistically different from control values in the male mice. However, food consumption in the 9018 ppm group was lower than controls on 29 of the 35 measurements obtained over the duration of the study.
In the females however, at 9018 ppm, body weight gain was reduced. The mean body weight in the 9018 ppm female group was significantly lower than control weights after week 29. By week 53 the 9018 ppm female mice weighed 14% lessthan the control mice. Similar to the males, mean food consumption values were not statistically different from control values in the mice exposed to the mid and low concentration of commercial hexane. However, in the 9018 ppm group, food consumption was lower than control values on 19 of the first 20 food consumption measurements at the beginning of the study.
Macroscopic examinations found an apparent treatment related increase in liver masses and nodules among the females in the 9018 ppm group but not among the males. There was a slight dose related decrease in the incidence of cysts in the uterus.
Microscopic examinations found a treatment related increase in hepatocellular neoplasm (adenoma and carcinoma) among females in the 9018 ppm group. Liver tumors among males were not treatment related. The incidence of liver tumors in the Group IV females is similar to the incidence in control males. Male mice of this strain have a higher spontaneous incidence of hepatocellular etumorsthan females.
There was also a treatment related decrease in the severity and a slight decrease in the incidence of cystic endometrial hyperplasia of the uterus among the females in the 9018 ppm group.
There was an increase in the incidence of pituitary proliferate changes(hyperplasia, adenoma and Aden carcinoma)among all treated groups of females but not among males. The treatment relationship of this observation is unclear because of a lack of dose response. The incidence of these changes is also within the historical range of data for control females.
In conclusion, under the exposure conditions of this study, commercial hexane is an oncogen in female mice. The NOEL for the neoplastic changes (hepatocellular tumors in females) was 3000 ppm.