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EC number: 250-882-8 | CAS number: 31981-44-9
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Gene mutation (Bacterial reverse mutation assay / Ames test) [similar to OECD 471]: negative with gestonorone caproate (Lang, 1978)
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 5. Oct - 14. Nov 1977
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: well reported pre-guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- no
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- histidin
- Species / strain / cell type:
- other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100 used for base pair substitutions and frame shift mutations.
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver homogenate (S9 mix)
- Test concentrations with justification for top dose:
- 0.005 - 2.5 mg/plate
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-AA, Benzo(a)pyren, MNNG
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 98, TA 1538 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- TA 1537 and TA 98 at highest concentration +S9
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- negative
- Executive summary:
ZK 5623 (gestonorone caproate) did not show a mutagenic potential in a bacterial reverse mutation assay (Ames test in S. typhimurium strains TA 98, TA 100, TA 1538, TA 1535 and TA1537) up to the highest tested concentration of 2.5 mg/plate (at which precipitates of test compound were observed) in the absence or presence of extrinsic metabolic activation (liver S9 mix from Aroclor 1254 -treated rats).
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- Justification for analogue approach:
As no acute toxicity data of gestonorone acetate is available, a read-across to gestonorone caproate (CAS 1253-28-7) was performed. A search for structure-analogue substances using the QSAR OECD Toolbox 4.0 recommended gestonorone caproate as one out of 19 category substances for a read-across approach (for additional information see QSAR OECD Toolbox Report on gestonorone acetate in "Attached justification"). Usually esters are hydrolysed in the presence of water or in organisms due to enzymatic degradation by esterases. As a result, the respective alcohol derivative (gestonorone (CAS 2137-18-0)) and carboxylic acid are generated. This is demonstrated by the QSAR toolbox 4.0 in the case of gestonorone acetate (CAS 2137-18-0) by the hydrolysis simulator (acidic, basic, neutral), the rat liver S9 metabolism simulator and the skin metabolism simulator. - Reason / purpose for cross-reference:
- read-across source
- Target gene:
- histidin
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 98, TA 1538 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- TA 1537 and TA 98 at highest concentration +S9
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- negative
- Executive summary:
ZK 5623 (gestonorone caproate) did not show a mutagenic potential in a bacterial reverse mutation assay (Ames test in S. typhimurium strains TA 98, TA 100, TA 1538, TA 1535 and TA1537) up to the highest tested concentration of 2.5 mg/plate (at which precipitates of test compound were observed) in the absence or presence of extrinsic metabolic activation (liver S9 mix from Aroclor 1254 -treated rats).
A read-across approach from gestonorone caproate to gestonorone acetate is justified by a OECD QSAR Toolbox structure analogue search.
Referenceopen allclose all
Gestonorone caproate did not show a mutagenic potential in the bacterial reverse mutation assay (Ames test in S. typhimurium strains TA98, TA 100, TA 1538, TA 1535 and TA1537) up to the highest tested concentration of 2.5 mg/plate (at which precipitates of test compound were observed) in the absence or presence of extrinsic metabolic activation (liver S9 mix from Aroclor 1254 -treated rats).
Gestonorone caproate did not show a mutagenic potential in the bacterial reverse mutation assay (Ames test in S. typhimurium strains TA98, TA 100, TA 1538, TA 1535 and TA1537) up to the highest tested concentration of 2.5 mg/plate (at which precipitates of test compound were observed) in the absence or presence of extrinsic metabolic activation (liver S9 mix from Aroclor 1254 -treated rats).
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
Dominant lethal test: negative with gestonorone caproate
Link to relevant study records
- Endpoint:
- in vivo mammalian germ cell study: cytogenicity / chromosome aberration
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- other information
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: pre-guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
- Deviations:
- no
- GLP compliance:
- no
- Type of assay:
- rodent dominant lethal assay
- Species:
- mouse
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- subcutaneous
- Duration of treatment / exposure:
- 7 weeks
- Frequency of treatment:
- twice weekly
- Post exposure period:
- no data
- Remarks:
- Doses / Concentrations:
2 - 20 - 200 mg/kg
Basis:
nominal conc. - No. of animals per sex per dose:
- no data
- Control animals:
- other: positive control: TEM in drinking water
- Tissues and cell types examined:
- Mating plug, pregnancy, number of death fetuses, total implants, bw,
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- not examined
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Conclusions:
- negative
- Executive summary:
No mutagenicity assay was performed with ZK 5624 (gestonorone acetate), results of studies with a different ester of gestonorone (gestonorone caproate, ZK 5623) are regarded as representative:
Results of a dominant-lethal test in mice with ZK 5623 did not indicate a mutagenic potential up to the highest tested dose of 200 mg/kg.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
There are no mutagenicity assays with ZK 5624 (gestonorone acetate), results of studies with a different ester of gestonorone (gestonorone caproate, ZK 5623) are regarded as representative.
A read-across approach fromgestonorone caproate to gestonorone acetate is justified by a OECD QSAR Toolbox structure analogue search:
ZK 5623 (gestonorone caproate) did not show a mutagenic potential in a bacterial reverse mutation assay (Ames test in S. typhimurium strains TA 98, TA 100, TA 1538, TA 1535 and TA1537) up to the highest tested concentration of 2.5 mg/plate (at which precipitates of test compound were observed) in the absence or presence of extrinsic metabolic activation (liver S9 mix from Aroclor 1254 -treated rats). (Lang 1978)
Results of a dominant-lethal test in mice with gestonorone caproate (ZK 5623) did not indicate a mutagenic potential up to the highest tested dose of 200 mg/kg. (Lang 1978)
A mutagenic potential of ZK 5623 is also not expected based on negative results with other steroid hormones in mutagenicity assays.
Justification for classification or non-classification
Based on the results there is no classification required according to Regulation (EC) 1272/2008 (CLP).
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