Registration Dossier

Administrative data

Description of key information

A registration of norethisterone was already submitted earlier and is public available on the ECHA website. Chapter 7, which is still valid from today's perspective, was amended to fulfill the current information requirements. Consequently the migrated data (IUCLID 5 to IUCLID 6) was kept unchanged and only modified if there was a need for further information and/or to pass the technical completeness check (TCC).

Norethisterone is a synthetic sex hormone and active ingredient of approved drugs since several decades. Norethisterone belongs to the category “steroidal progestins” and has progestogenic properties resembling those of the naturally occuring progesterone but is a more potent inhibitor of ovulation. Apart from the data on norethisterone, information from its ester derivates (norethisterone enanthate and acetate) can be used for characterization of the biological activity of progestin, because both esters are rapidly cleaved within the mammalian organism and thus, norethisterone is the systemically active metabolite irrespective of the form which is administered.

Neither in vivo studies in animals nor in vivo studies on skin sensitisation are available for norethisterone. Data waivers are claimed. The vast amount of clinical experience gained with this approved drug substance over many decades gives no evidence that norethisterone and related substances (norethisterone enanthate/acetate) have a significant skin sensitizing potential.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
Norethisterone and its ester derivates (norethisterone enanthate/acetate) are well-known drug substances and constituents of numerous approved drug products which have been in therapeutic use for many decades and therefore the formal data gap is more than compensated by the vast amount of clinical experience gained in their continued and widespread therapeutic use.
Overall there is proven broad exposure related to the therapeutic topical use of norethisterone related substances in transdermal therapeutic systems and there is only one isolated positive patch test reaction of unclear relevance published, compared to the substantial therapeutic use in postmenopausal patients.
Therefore based on the available reliable and relevant human data the assessment of the skin sensitization potential (hazard identification) is possible. Based on all available data there is no evidence of skin sensitization properties of norethisterone and structurally related substances.
Endpoint:
skin sensitisation: in vivo (LLNA)
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
Norethisterone and its ester derivates (norethisterone enanthate/acetate) are well-known drug substances and constituents of numerous approved drug products which have been in therapeutic use for many decades and therefore the formal data gap is more than compensated by the vast amount of clinical experience gained in their continued and widespread therapeutic use.

Overall there is proven broad exposure related to the therapeutic topical use of norethisterone related substances in transdermal therapeutic systems and there is only one isolated positive patch test reaction of unclear relevance published, compared to the substantial therapeutic use in postmenopausal patients.
Therefore based on the available reliable and relevant human data the assessment of the skin sensitization potential (hazard identification) is possible. Based on all available data there is no evidence of skin sensitization properties of norethisterone and structurally related substances.



Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

For additional information see expert opinion " Assessment of the skin sensitization potential of Norethisterone (CAS 68-22-4) and related substances" in chapter 7.10.4 Sensitisation data (humans).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In the light of the clinical experience no classification is required according to Regulation (EC) No. 1272/2008 (CLP).