Decalin is used as an industrial
solvent for
naphthalene,
fats, resins,
oils, and
waxes. It is also used as a substitute for
turpentine in lacquers, paints, and varnishes; as a
solvent and stabilizer for shoe polishes and floor
waxes; and as a constituent of motor fuels and
lubricants. Other applications include use as a paint thinner and remover, a patent fuel in stoves, a high-density fuel in submarine-launched cruise missile systems, and in
stain removal and cleaning machinery.
Decalin was nominated for study by the National Cancer Institute because of its chemical structure, its potential for consumer exposure, and a lack of adequate testing of the chemical. Male and female F344/N rats and B6C3F(1) mice were exposed to
decalin (greater than 99% pure) by inhalation for 2 weeks, 3 months, or 2 years. Groups of male NBR rats were exposed to
decalin for 2 weeks. Male NBR rats do not produce
alpha2u-globulin; the NBR rats were included to study the relationship of alpha2u-globulin and renal lesion induction. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. 2-WEEK STUDIES IN RATS: Groups of five male and five female F344/N rats and five male NBR rats were exposed to 0, 25, 50, 100, 200, or 400 ppm
decalin vapor 6 hours per day, 5 days per week for 16 days. All rats survived to the end of the study, and mean
body weights of exposed groups were similar to those of the chamber controls. Renal toxicity studies were performed in male F344/N and NBR rats. The numbers of labeled cells and the labeling indices in the left kidney of 200 and 400 ppm F344/N male rats were significantly greater than those in the chamber controls. The
alpha2u-globulin/soluble
protein ratios were significantly increased in all exposed groups of F344/N rats. Liver weights of male F344/N and NBR rats exposed to 100 ppm or greater were significantly increased, as were those of all exposed groups of females. Kidney weights of male F344/N rats exposed to 50 ppm or greater were significantly increased. Exposure-related hyaline droplet accumulation, degeneration and regeneration of renal cortical tubules, and granular casts occurred in the kidney of exposed F344/N male rats. 2-WEEK STUDIES IN MICE: Groups of five male and five female B6C3F(1) mice were exposed to 0, 25, 50, 100, 200, or 400 ppm
decalin vapor 6 hours per day, 5 days per week for 17 days. All mice survived to the end of the study, and mean
body weights of exposed groups were similar to those of the chamber control groups. Liver weights of 200 and 400 ppm males and females and 100 ppm females were significantly increased. 3-MONTH STUDY IN RATS: Groups of 25 male and 20 female F344/N rats were exposed to 0, 25, 50, 100, 200, or 400 ppm
decalin vapor 6 hours per day, 5 days per week for 2 (five male renal toxicity rats), 6 (10 male and 10 female clinical pathology rats), or 14 (10 core study rats) weeks. All rats survived to the end of the study, and mean
body weights of exposed groups were similar to those of the chamber control groups. Urinalysis results indicated that
decalin exposure caused increases in urine
glucose and
protein concentrations and
enzyme activities that were consistent with the renal lesions observed microscopically. Renal toxicity studies were performed on rats sacrificed at 2 and 6 weeks and at the end of the study. In kidney tissue examined for cell proliferation, the numbers of
PCNA-labeled cells and labeling indices were generally significantly greater than those of the chamber controls in exposed groups of rats at all three time points. Concentrations of alpha2u-globulin in the kidney as well as the
alpha2u-globulin/soluble
protein ratios were significantly increased at week 2 in all exposed groups and in the 200 and 400 ppm groups at week 6 and at the end of the study. Absolute and/or relative kidney and liver weights of male rats exposed to 50 ppm or greater were increased. Incidences of renal tubule regeneration and granular casts in the medulla of the kidney in exposed male rats were increased, and the severities of hyaline droplets generally increased with increasing exposure concentration. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female B6C3F(1) mice were exposed to 0, 25, 50, 100, 200, or 400 ppm
decalin vapor 6 hours per day, 5 days per week for 14 weeks. All mice survived to the end of the study, and mean
body weights of exposed groups were similar to those of the chamber control groups. Liver weights of 200 and 400 ppm males and females were significantly increased. There was a significant exposure concentration-related decrease in the absolute spermatid head count and a significant decrease in absolute head count of the 400 ppm group compared to the chamber controls. Incidences of centrilobular cytomegaly of the liver were increased in exposed male mice. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female F344/N rats were exposed to 0, 25, 50 (male rats only), 100, or 400 ppm (female rats only)
decalin vapor 6 hours per day, 5 days per week for 105 weeks. A group of 20 male rats was exposed to 400 ppm. Survival of exposed groups was similar to that of the chamber control groups. Mean
body weights of 400 ppm males were slightly less than those of the chamber controls during the second year of the study. Incidences of renal tubule
adenoma and
adenoma or
carcinoma (combined) and of benign or malignant
pheochromocytoma (combined) of the adrenal medulla in 100 and 400 ppm males were significantly increased. There was a significant association between nephropathy severity and adrenal
pheochromocytoma incidence. Nonneoplastic lesions related to
decalin exposure occurred in the kidney of male rats. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female B6C3F(1) mice were exposed to 0, 25, 100, or 400 ppm
decalin vapor 6 hours per day, 5 days per week for 105 weeks. Survival of exposed mice was similar to that of the chamber controls. Mean
body weights of exposed groups were generally similar to those of the chamber control groups throughout the study. Increased incidences of hepatocellular
neoplasms occurred in 25 and 400 ppm female mice, and the incidences of centrilobular
hypertrophy,
necrosis, syncytial alteration, and erythrophagocytosis of the liver in 400 ppm males were significantly increased. The incidences of uterine stromal
polyp and stromal
polyp or stromal
sarcoma (combined) occurred with positive trends in female mice.
PHARMACOKINETIC MODEL: