Registration Dossier

Administrative data

Description of key information

In a read-across study, Fischer 344 rats and CD-1 mice were exposed to 0, 500, 2500 or 5000 ppm (0, 1229, 6145 or 12290 mg/m3) of Isopropanol vapor, 6 hours/day, 5 days/week for 78 weeks (mice) or 104 weeks (rats). No increased incidence of neoplastic lesions were observed in mice and female rats. There was a statistically significant increase in Leydig cell tumors in male rats, a common spontaneous neoplasm in aged rats of this strain. In addition, the authors indicated that this statistically significant increase was most likely due to the unusually low incidence in controls and hence not considered relevant to human risk. 

Key value for chemical safety assessment

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
12 290 mg/m³
Study duration:
chronic
Species:
other: rat/mice

Additional information

In the absence of a chronic toxicity study for sBA, an existing study on isopropanol (IPA) was used as read-across. A read-across justification for IPA is provided in an attachment in Section 13 of this dossier. In a long-term toxicity study of IPA, groups of male/female F-344 rats and CD-1 mice were exposed to vapor at target concentrations of 0, 500, 2500 or 5000 ppm, 6 hours/day, 5 consecutive days/week for 78 weeks (mice) or 104 weeks (rats) (Burleigh-Flayer et al., 1997). Chronic IPA exposure produced clinical signs of toxicity, changes in body weight and urinalysis and urine chemistry indicative of kidney effects 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) 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 the male F-344 rat strain. 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 was noted in female rats or male/female mice.

 

 

Additional References

 

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.

 

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.