Propan-2-ol

Endpoint summary

Description of key information

GLP-guideline study according to OECD guideline 451 in rats is available for IPA. The derived NOAEC is 5000 ppm.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

12 500 mg/m³

Additional information

A GLP whole-body inhalation oncogenicity study in Fischer 344 rats with IPA concentrations of 0, 500, 2500, 5000 ppm for 6 hours/day 5 days/week for 104 weeks was conducted according to OECD test guideline 451. The report allows to conclude on a NOAEL = 5000 ppm.Exposure of rats to isopropanol vapor for 24 months produced clinical signs of toxicity, changes in body weight, and urinalysis and urine chemistry indicative of kidney changes in the 2500 and 5000 ppm groups. These changes were considered by the study authors to be indicative of chronic progressive nephropathy, a spontaneous lesion in aging rats which tends to be more prominent in male than female rats. Based on human and animal evidence relating to CPN, Hard et al. (2009;Gordon C. Hard, Kent J. Johnson, Samuel M. Cohen; Critical Reviews in Toxicology; 2009, Vol. 39, No. 4, Pages 332-346; A comparison of rat chronic progressive nephropathy with human renal disease) have concluded that this is a rodent-specific lesion which should not be regarded as an indicator of human toxic hazard. The only neoplastic lesion which was elevated was an increase in Leydig cell tumors in male rats.This is also a common spontaneous lesion in male rat which is very common in the rat strain used for this evaluation, F-344. The authors observed that the statistical significance attached to the frequency of this observation was probably due to the unusually low incidence in the concurrent control group. No increase in neoplastic lesions were noted in female rats.

A shorter duration key study was a subchronic inhalation study in Fischer 344 rats and CD-1 mice with IPA administered at concentrations of 0, 500, 2500, 5000 ppm for 6 hours/day 5 days/week for 98 days (Burleigh-Flayeret al.,1991). This GLP study was conducted according to OECD test guideline 413. During the 14th week, male and female rats (excluding those animals designated for neuroanatomic pathology evaluation) received 2 and 3 consecutive days of exposure, respectively. The 10 female rats of the 500, 1500, and 5000 ppm group designated for neuroanatomic pathology evaluation were exposed for 1 day during the 14th week; the male rats of the 500, 1500, and 5000 ppm group designated for neuroanatomic pathology evaluation were not exposed during the 14th week. Male and female mice received 4 and 5 consecutive days of exposure during the 14th week, respectively. NOAECs were not identified by the authors. Rats showed acute signs of toxicity (including ataxia, narcosis, lack of a startle reflex, and/or hypoactivity), decreases in absolute body weight and body weight gain, and changes in hematology parameters in animals exposed to 1500 and 5000 ppm of isopropanol, increased relative liver weight in male and female rats exposed to 5000 ppm, as well as increased motor activity for female rats in the 5000 ppm group. Mice showed clinical signs of acute toxicity (including ataxia, narcosis, lack of a startle reflex, and/or hypoactivity) in animals exposed to 1500 and 5000 ppm of isopropanol, increased body weight and body weight gain observed in female mice of the 5000 ppm group, various changes in hematologic and serum clinical chemistry parameters observed in female mice of the 5000 ppm group, and increased relative liver weight in female mice of the 5000 ppm group.

Supportive information on the repeated dose inhalation toxicity of IPA also is provided. A 78-week inhalation oncogenicity study (GLP and based on OECD test guideline 453) in CD-1 mice identified a NOEL[equivalent to a no-observed effect concentration (NOEC)] for toxic effects of 500 ppm due to clinical signs of toxicity and increases in body weights and body weight gains noted at the higher doses, and a NOEL for oncogenicity effects of 5000 ppm (the highest dose tested) as an increased frequency in neoplastic lesions was not noted (Burleigh-Flayer and Wagner, 1993). A 9-day inhalation study in Fischer 344 rats and CD-1 mice conducted according to OECD test guideline 412 was conducted according to GLP (Burleigh-Flayer et al., 1990). Animals were administered IPA for 6 hours/day, 5 days/week at 1000, 5000, 10000, and 15000 ppm. Mortality was observed in rats and mice at the highest two doses. Histologic lesions observed in the kidneys of male rats at 1000 and 5000 ppm are considered to be species and sex specific.

Justification for classification or non-classification

The substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) NO. 1272/2008.