National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/7721

Abstract for TR-513 - Decalin (CASRN 91-17-8)

ABSTRACT

Toxicology and Carcinogenesis Studies of Decalin (CAS No. 91-17-8) in F344/N Rats and B6C3F1 Mice and a Toxicology Study of Decalin in Male NBR Rats (Inhalation Studies)

Link to the full study report in PDF. If you have difficulty accessing the document, please send email to the NTP Webmaster [ Send Email ] and identify documents/pages for which access is required.  

 

 

Chemical Formula: C10H18

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 submarinelaunched 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 B6C3F1 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 α2u-globulin; the NBR rats were included to study the relationship of α2u-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 α2u-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 B6C3F1 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 α2u-globulin in the kidney as well as the α2u-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 B6C3F1 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 B6C3F1 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

The rate of metabolism of decalin was the same for males and females in rats and mice. Also in rats and mice, decalin metabolism was saturated at less than 400 ppm. Increased labeling indices in male rats were likely due to changes related to α2u-globulin.

GENETIC TOXICOLOGY

Decalin was not mutagenic in S. typhimurium strains TA97, TA98, TA100, or TA1535, with or without induced hamster or rat liver S9 enzymes. A small but significant increase in the frequency of micronucleated normochromatic erythrocytes was noted in male mice exposed to decalin for 3 months; however, no induction of micronuclei was observed in female mice.

CONCLUSIONS

Under the conditions of these studies, there was clear evidence of carcinogenic activity of decalin in male F344/N rats based on increased incidences of renal tubule neoplasms. The increased incidences of benign or malignant pheochromocytoma (combined) of the adrenal medulla in male rats were also considered to be exposure related. There was no evidence of carcinogenic activity of decalin in female F344/N rats exposed to 25, 100, or 400 ppm. There was no evidence of carcinogenic activity of decalin in male B6C3F1 mice exposed to 25, 100, or 400 ppm. There was equivocal evidence of carcinogenic activity of decalin in female B6C3F1 mice based on marginally increased incidences of hepatocellular and uterine neoplasms.

Exposure of male rats to decalin resulted in nonneoplastic lesions of the kidney characteristic of α2u-globulin accumulation. Nonneoplastic lesions of the liver were observed in male mice exposed to decalin.

Synonyms: Bicyclo[4.4.0]decane; dec; decahydronaphthalene; dekalin; naphthalane; napthan; napthane; perhydronaphthalene

 

Summary of the 2-Year Carcinogenesis Studies of Decalin

 

Male
F344/N Rats

Female
F344/N Rats

Male
B6C3F1 Mice

Female
B6C3F1 Mice

Concentrations in air

Chamber control, 25, 50, 100, or 400 ppm

Chamber control, 25, 100, or 400 ppm

Chamber control, 25, 100, or 400 ppm

Chamber control, 25, 100, or 400 ppm

Body weights

400 ppm group slightly less than the chamber control group

Exposed groups similar to the chamber control group

Exposed groups similar to the chamber control group

Exposed groups similar to the chamber control group

Survival rates

28/50, 23/50, 23/49, 20/50, 14/20

32/50, 35/50, 39/50, 28/50

40/50, 41/50, 36/50, 34/50

37/49, 28/50, 35/50, 36/50

Nonneoplastic effects

Kidney: severity of chronic nephropathy (1.4, 2.3, 2.6, 2.3, 3.0); renal tubule hyperplasia (0/50, 11/50, 11/49, 15/50, 5/20); hyaline droplet accumulation (2/50, 9/50, 7/49, 11/50, 2/20); renal papilla mineralization (1/50, 34/50, 41/49, 43/50, 17/20); pelvic transitional epithelium hyperplasia (1/50, 8/50, 8/49, 10/50, 5/20)

None

Liver: eosinophilic focus (10/50, 9/50, 7/50, 19/50); centrilobular hypertrophy (2/50, 0/50, 4/50, 36/50); necrosis (0/50, 1/50, 3/50, 19/50); syncytial alteration (26/50, 28/50, 36/50, 44/50); erythrophagocytosis (0/50, 0/50, 0/50, 9/50)

None

Neoplastic effects

Kidney: renal tubule adenoma (1/50, 2/50, 6/49, 9/50, 5/20); renal tubule adenoma or carcinoma (1/50, 3/50, 7/49, 12/50, 6/20)

Adrenal medulla: benign or malignant pheochromocytoma (8/49, 9/49, 13/49, 16/49, 8/20)

None

None

None

Equivocal Findings

None

None

None

Liver: hepatocellular adenoma (7/49, 13/50, 8/50, 17/50); hepatocellular carcinoma (4/49, 16/50, 6/50, 5/50); hepatocellular adenoma or carcinoma (11/49, 27/50, 14/50, 20/50)

Uterus: stromal polyp (0/49, 0/50, 2/50, 3/50); stromal polyp or stromal sarcoma (0/49, 0/50, 2/50, 4/50)

Level of evidence of carcinogenic activity

Clear evidence

No evidence

No evidence

Equivocal evidence

Genetic Toxicology of Decalin
Assay Test System Results
Bacterial Mutagenicity Salmonella typhimuriumgene mutations: Negative in strains TA97, TA98, TA100, and TA1535 with and without S9
Micronucleated erythrocytes Mouse peripheral blood in vivo: Positive in male mice; negative in female mice

Report Date: January 2005

Pathology Tables, Survival and Growth Curves from NTP 2-year Studies

Target Organs & Incidences from 2-year Studies

 


Return to Long Term Abstracts

NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.