Octyl (R)-2-(4-chloro-2-methylphenoxy)propionate

Carcinogenicity

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

chronic

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No classification is warranted for cancerogenicity according to Regulation (EC) No 1272/2008, Annex I.

Additional information

Studies on carcinogenicity are not a standard requirement according to REACH for the tonnage band 100-1000 t/a.

No such study is available for Mecoprop-P n-octyl ester, but data are available for Mecoprop-P acid (MCPP-P acid), which is the hydrolysis product of Mecoprop-P n-octyl ester, and are thus included in this chapter.

A comparison of the data from repeated dose studies show that for systemic toxicity the compounds have very similar toxicological profiles with respect to dose level and target organ. This is based on the fact, that Mecoprop-P n-octyl ester is in vivo rapidly metabolised to Mecoprop-P acid (MCPP-P acid) and the corresponding alcohol, and thus systemic toxicity is finally determined by the same species. A full and elaborated justification for the read across is attached to this endpoint summary.

For Mecoprop-P both studies of the racemate (Mecoprop) and of the R-isomer (Mecoprop-P) are relevant, and included in this chapter. The relevance was confirmed by the Mecoprop-P rapporteur Member State Denmark, represented by the Danish Environmental Protection Agency (SANCO/3065/99-Final, 2003).

The available data from read across are 2-year carcinogenicity studies on rats and mice.

One is a combined chronic toxicity/carcinogenicity study according to OECD TG 453 was conducted on rats. Diet contained 0, 20, 100 and 400 ppm Mecoprop (racemic). No histopathological and neoplastic changes were found. The NOAEL for general toxicity was set in this study to 100 ppm due to effects on kidneys (increased organ weight, increased level of urea).

 

Furthermore a cancerogenicity study with Mecoprop-P (R-isomer) on mice is available. In this study according to OECD TG 451 mice were fed with diets containing 0, 25, 250 or 2500 ppm for 18 months. However, the highest dose group was killed after 12 months and not investigated further, due to severely affected body weight gain. At 250 ppm increased kidney weight was seen in females and they had chronic nephropathy. No substance-related toxic effects were concluded for males. Therefore, the NOAELs for toxicity were set to 25 ppm for females and 250 ppm for males. As a maximum tolerated dose (MTD) was not reached for male mice in this study a supplemental feeding study of further 18 months was conducted with dose levels of 700 ppm for male mice and 800 ppm for female mice. For both sexes impairment of body weight/body weight change was observed until the end of the study. Significant increase of the mean relative kidney weights in males and females were found; furthermore increased numbers of male and female mice with chronic nephropathy and slightly increased degree of severity of this finding. Thus, toxic signs fulfilling the criteria for an MTD were seen in males and females. An indication for a cancerogenic potential of the substance was also not found in this supplemental study.

 

Based on the read across to Mecoprop-P acid (MCPP-P acid) no potential for carcinogenicity is concluded for Mecoprop-P n-octyl ester.

Justification for selection of carcinogenicity via oral route endpoint:
No study was selected here, because the available data on carcinogenicity (studies on rats and mice) were all relevant. In any case no indication for a carcinogenetic potential was concluded from the studies.