Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
genetic toxicity in vivo, other
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
With regard to Column 2 section 8.4. "Appropriate in vivo mutagenicity studies shall be considered in case of a positive result in any of the genotoxicity studies in Annex VII or VIII." On the other hand Information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.
Adaption of standard testing regime in accordance with the general rules set out in REACH Regulation EC No. 1907/2006 Annex XI:

Section 1. “Use of existing data”

1.1.3. “Historical human data” - estrone is an endogenous sex hormone and an approved drug since several decades

and

1.5. “Grouping of substances" – estrone belongs to the category “steroidal estrogens”

and

1.5 "read-across approach" - estradiol-17ß is a surrogate for estrone because circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. 17β-estradiol is converted reversibly to estrone. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone, at the receptor level.

Estrone is a natural estrogen hormone and approved drug and the ICH ( International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) core battery of tests (Ames, chromosomen aberration in vitro, MNT, in vivo) were mentioned to be negative (Joosten H.F.P. et al., Toxicology Letters 151, 113-134 (2004). In addition Estrone is a member of a steroid class (= steroidal estrogens) and therefore its genotoxic hazard should not be assessed in isolation. Therefore the decision whether further testing is appropiate should imply all available data for the steroid class and the already existing self classification.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion