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Toxicological information

Carcinogenicity

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Description of key information

2 studies are available on the carcinogenicity of Dibromoneopentyl Glycol via the oral route:
1.      National Toxicology program, (May 1996): NTP Technical Report on the Toxicology and Carcinogenesis Studies of 2,2-bis(bromomethyl)-1,3-propanediol (FR-1138, CAS No. 3296-90-0) in F344/N Rats and B6C3F1 Mice.
 2.     Keyes et al. (1980): ‘Results of a two year toxicity and oncogenicity study of rats ingesting diets containing dibromoneopentyl glycol (FR-1138)’.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
LOAEL
35 mg/kg bw/day

Additional information

Groups of male and female F344/N rats and B6C3F mice were exposed to technical grade of 2,2-bis(bromoneopentyl)-1,3-propanediol (78%) pure) in feed for 2 years.

2-Year Study in Rats

Groups of 60 male and 60 female rat received 2,500, 5000, or 10,000ppm of 2,2-bis(bromoneopentyl)-1,3-propanediol in feed for 104 weeks. Groups of 70 males and 60 females received 0ppm test substance in feed for 104 weeks. A stop-exposure group of 70 male rats received 20,000ppm test substance in feed for 3 months, after which animals received undosed feed for the remainder of the 2- year study. Average daily doses of the test substance were 100, 200, or, 430 mg/kg bw for males and 115, 230, or, 460 mg/kgbw for females. Stop-exposure males received an average daily dose of 800 mg/kg. Ten animals from the 0ppm male group and the 20,000ppm stop-exposure group were evaluated at 3 months. Ten control animals and 10 animals from each of the continuous-exposure groups were evaluated at 15 months.

Survival, Body weights, feed consumption, and Clinical Findings:

Survivalof 5000ppm and 10,000ppm continuous-exposure study males and females and 20,000ppm stop-exposure males was significantly lower than that of the controls.

Mean body weightsof exposed male and female rats receiving10,000ppm and 20,000ppm stop-exposure males were lower those of the controls throughout most of the study.

Feed consumption-In the continuous-exposure study, feed consumption exposed rats was generally similar to that by the controls thought the study. In 20,000ppm stop-exposure males, the feed consumption was lower than by that by the controls.

Clinical findingsincluded skin and/ or subcutaneous masses of face, tail and the ventral and dorsal surfaces of exposed rats. 

Pathology Findings:

In the 2-year continuous and stop-exposure studies in male rats, exposure to 2,2-bis(bromoneopentyl)-1,3-propanediol was associated with neoplastic effects in the skin, mammary, gland, and Zymbal gland, oral cavity esophagus, forestomach, , small and large intestines, mesothelium, urinary bladder, lung, thyroid gland hematopietic system, and seminal vesicle. Nonneoplastic effects in the kidney , lung, thyroid gland, seminal vesicle, pancreas, urinary bladder, and forestomach were also observed. These findings are outlined in the two summary tables.

 

2-Year Study in Mice

Groups of 60 male and 60 female mice received 0, 312, 625, or 1250ppm of 2,2-bis(bromoneopentyl)-1,3-propanediol in feed for 104 weeks. Average daily doses of the test substance were 35, 70, or, 140 mg/kg bw (males) and 40, 80, or, 170 mg/kgbw (females). Ten animals from each group were evaluated at 15 months.

Survival, Body weights, feed consumption, and Clinical Findings:

Survivalof 1250ppm males females was significantly lower than that of the controls.

Mean body weightsof exposed male and female were lower those of the controls throughout most of the study. Final mean body weights were also generally similar to those of controls.

Feed consumption-by exposed male and female mice was similar to that by controls.

Clinical findings- included tissue masses involving the eye in exposed mice.

 

Pathology Findings

Exposure of male mice to 2,2-bis(bromoneopentyl)-1,3-propanediol for 2 years was associated with neoplastic effects in the harderian gland, lung, and kidney. Exposure of male mice to 2,2-bis(bromoneopentyl)-1,3-propanediol was associated with increased incidences of neoplasms of the harderian gland, lung, and skin. Nonneoplastic effects in the lung were also observed. These findings are outlined in the two summary tables.

There was clear evidence of carcinogenic activity of the test substance in male F344/N rats based on increased incidences of neoplasms of the skin, subcutaneous tissue, mammary gland, Zymbal’s gland, oral cavity, esophagus, forestomach, small and large intestines, mesothelium, urinary bladder, lung, thyroid gland and seminal vesicle, and the increased incidence of mononuclear cell leukemia. There was clear evidence of carcinogenic activity of the substance in female F344/N rats based on increased incidences of neoplasms of the oral cavity, esophagus, mammary gland and thyroid gland. There was clear evidence of carcinogenic activity of the substance in male B6C3F1 mice based on increased incidences of neoplasms of the harderian gland, lung and kidney. There was clear evidence of carcinogenic activity of the substance in female B6C3F1 mice based on increased incidences of neoplasms of the harderian gland, lung and subcutaneous tissue. Slight increases in the incidences of neoplasms in the pancreas and kidney in male mice and the forestomach, mammary gland and circulatory system in female mice may also have been related to treatment.

Justification for classification or non-classification

Based on the findings of the NTP study (1991), the substance is classified according to GHS as Carcinogenic Category 2

 H351: Suspected of causing cancer.