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Directorate-General for Health and Food Safety
Summary sheet on Commission
Review (ref. XXIV/1990/97)
Ingredient : 11 Alpha-hydroxypregn-4-ene, 3,20 dione
CAS n° : 80-75-1; 41338-98-6 (hemisuccinate)
Function and max in use concentration : antiandrogenic, antiseborrhoeic agent 0,5 %
Assessment of acute toxicity (i.p.) : i.p. toxicity low
Assessment of irritation & corrosivity :
- Inadequate data on skin and mucous membrane irritation
- No harmful effects on human skin in normal conditions of use.
Assessment of allergenicity/sensitivity:
- Lack of data on skin sensitisation.
Assessment of chronic/sub-chronic toxicity:
- Lack of data on sub-chronic and chronic toxicity; no available NOAEL.
Percutaneous absorption:
- Permeation rate of the same order of magnitude as progesterone.
Assessment of genotoxicity/carcinogenicity:
- Lack of data on genotoxicity
- Inadequate data on carcinogenicity.
Assessment on reproductive toxicity:
- No data.
Assessment on endocrine activity:
- Mineralocorticoïd like effects in vitro and in vivo
- Some antiandrogenic or antioestrogenic effects.
Classification: 2a
SCCNFP Opinion
The available toxicological data are insufficient as to support the safe use of 11alpha-Hydroxypregn-4-ene, 3,20 dione (11alpha- OHP) in cosmetic products. However it is known that 11alpha- OHP is not irritant to human skin, and that its percutaneous absorption is of the same order of magnitude as progesterone.
It appears probably that the purity grade - the progesterone content - of 11alpha- OHP participates in some of the endocrine activities observed. Very recent studies have shown that 11alpha- OHP is a very potent inhibitor of the glucocorticoïd inactivating enzymes 11 beta-Hydroxysteroïd dehydrogenases in vitro and conferred potent mineralocorticoïd activity at low doses in adrenalectomized rats. These effects were shown to be mediated via mineralocorticoïd receptors and could be correlated with potent hypertensive effects.
The SCC is of the opinion that 11alpha- OHP and its esters must not be used in cosmetic products.
Statement on the toxicological evaluation
The SCCNFP is the scientific advisory body to the European Commission in matters of consumer protection with respect to cosmetics and non-food products intended for consumers.
The Commission's general policy regarding research on animals supports the development of alternative methods to replace or to reduce animal testing when possible. In this context, the SCCNFP has a specific working group on alternatives to animal testing which, in co-operation with other Commission services such as ECVAM (European Centre for Validation of Alternative Methods), evaluates these methods.
SCCNFP opinions include evaluations of experiments using laboratory animals; such tests are conducted in accordance with all legal provisions and preferably under chemical law regulations. Only in cases where no alternative method is available will such tests be evaluated and the resulting data accepted, in order to meet the fundamental requirements of the protection of consumer health.
Ingredient : 11 Alpha-hydroxypregn-4-ene, 3,20 dione
CAS n° : 80-75-1; 41338-98-6 (hemisuccinate)
Function and max in use concentration : antiandrogenic, antiseborrhoeic agent 0,5 %
Assessment of acute toxicity (i.p.) : i.p. toxicity low
Assessment of irritation & corrosivity :
- Inadequate data on skin and mucous membrane irritation
- No harmful effects on human skin in normal conditions of use.
Assessment of allergenicity/sensitivity:
- Lack of data on skin sensitisation.
Assessment of chronic/sub-chronic toxicity:
- Lack of data on sub-chronic and chronic toxicity; no available NOAEL.
Percutaneous absorption:
- Permeation rate of the same order of magnitude as progesterone.
Assessment of genotoxicity/carcinogenicity:
- Lack of data on genotoxicity
- Inadequate data on carcinogenicity.
Assessment on reproductive toxicity:
- No data.
Assessment on endocrine activity:
- Mineralocorticoïd like effects in vitro and in vivo
- Some antiandrogenic or antioestrogenic effects.
Classification: 2a
SCCNFP Opinion
The available toxicological data are insufficient as to support the safe use of 11alpha-Hydroxypregn-4-ene, 3,20 dione (11alpha- OHP) in cosmetic products. However it is known that 11alpha- OHP is not irritant to human skin, and that its percutaneous absorption is of the same order of magnitude as progesterone.
It appears probably that the purity grade - the progesterone content - of 11alpha- OHP participates in some of the endocrine activities observed. Very recent studies have shown that 11alpha- OHP is a very potent inhibitor of the glucocorticoïd inactivating enzymes 11 beta-Hydroxysteroïd dehydrogenases in vitro and conferred potent mineralocorticoïd activity at low doses in adrenalectomized rats. These effects were shown to be mediated via mineralocorticoïd receptors and could be correlated with potent hypertensive effects.
The SCC is of the opinion that 11alpha- OHP and its esters must not be used in cosmetic products.
Statement on the toxicological evaluation
The SCCNFP is the scientific advisory body to the European Commission in matters of consumer protection with respect to cosmetics and non-food products intended for consumers.
The Commission's general policy regarding research on animals supports the development of alternative methods to replace or to reduce animal testing when possible. In this context, the SCCNFP has a specific working group on alternatives to animal testing which, in co-operation with other Commission services such as ECVAM (European Centre for Validation of Alternative Methods), evaluates these methods.
SCCNFP opinions include evaluations of experiments using laboratory animals; such tests are conducted in accordance with all legal provisions and preferably under chemical law regulations. Only in cases where no alternative method is available will such tests be evaluated and the resulting data accepted, in order to meet the fundamental requirements of the protection of consumer health.
