NITE - Chemical Management Field

Latest GHS Classification Results by the Japanese Government (edited by NITE)

GENERAL INFORMATION

Item	Information
CAS RN	53-16-7
Chemical Name	1,3,5(10)-Estratrien-3-ol-17-one [Estrone]
Substance ID	m-nite-53-16-7_v1
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	To Guidance List
UN GHS document (External link)	To UN GHS document
FAQ（GHS classification results by the Japanese Government）	To FAQ
List of Information Sources (Excel file)	List of Information Sources
List of Definitions/Abbreviations	Definitions/Abbreviations
Sample Label by MHLW (External link)	MHLW Website (in Japanese Only)
Sample SDS by MHLW (External link)	MHLW Website (in Japanese Only)
OECD/eChemPortal (External link)	To OECD/eChemPortal (External link)

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Flammable solids	Classification not possible	- -	-	-	No data available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified (Not applicable)	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances are not available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
17	Desensitized explosives	-	- -	-	-	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Acute toxicity (Oral)	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Vapours)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Skin corrosion/irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Skin sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Germ cell mutagenicity	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	This substance (synonyms: estrone) is one of the estrogens and is used for the treatment of post-menopausal women, etc. (Ethical Pharmaceuticals 2017 (2016), HSDB (Access on August 2017)). In humans, although it is not confined to this substance alone, there is a report that the risk of women developing breast cancer rose significantly when conjugated estrogens (combination drug of sodium estrone sulfate, sodium equilin sulfate, and sodium 17 alpha-dihydroequilin sulfate) were administered to hysterectomized patients, or when conjugated estrogen and progestagen were used in combination (Ethical Pharmaceuticals 2017 (2016)). It is reported in multiple cohort studies and case studies that the risk of breast cancer and endometrial cancer increased in post-menopausal estrogen therapy with female hormone preparations, and IARC classified post-menopausal estrogen therapy in Group 1 (IARC 72 (1999)). In experimental animals, in any of the tests in which the substance was administered to castrated male mice in drinking water or feeding, to untreated male mice by dermal or subcutaneous/intramuscular dosing, and to castrated male rats or ovariectomized female rats by subcutaneous/intramuscular dosing, higher incidences of the mammary tumors were observed (IARC 21 (1979), IARC 72 (1999)). Moreover, in a subcutaneous administration test with untreated male and female rats, in addition to mammary tumors, pituitary tumors were observed in all cases, and malignant tumors in the kidney and pituitary adenomas were observed in a subcutaneous/intramuscular administration test with castrated male hamsters (IARC 21 (1979), IARC 72 (1999)). IARC concluded that there is sufficient evidence in experimental animals for carcinogenicity of estradiol and this substance (IARC 72 (1999)). From the above, it was classified in Category 1A for this hazard class.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Reproductive toxicity	Category 1A	Danger	H360	P308+P313 P201 P202 P280 P405 P501	This substance (synonyms: estrone) is one of the estrogens and is used for the treatment of post-menopausal women, etc. (Ethical Pharmaceuticals 2017 (2016), HSDB (Access on August 2017)). In humans, although it is not confined to this substance alone, conjugated estrogens (combination drugs of sodium estrone sulfate, sodium equilin sulfate, and sodium 17 alpha-dihydroequilin sulfate) are contraindicated for pregnant women or women who have possibility of pregnancy (pregnant woman, parturient woman, nursing women) because safety has not been established (Ethical Pharmaceuticals 2017 (2016)). In experimental animals, there are reports as follows: as a result of subcutaneous administration to pregnant rats at 0.02 mg/animal at the early phase of gestation (before the implantation of fertilized egg) or 0.0175 mg/kg/day on gestational days 1-7, the pregnancy was terminated; as a result of subcutaneous administration of 0.02-0.05 mg/kg/day to pregnant rats on gestational days 2-4, a dose-dependent decrease of a conception rate was observed; as a result of single subcutaneous administration of 0.4 mg/kg to pregnant rats on any of gestational days 8-11, marked reduction in the number of surviving fetuses and delayed delivery were observed; as a result of single subcutaneous administration of 0.14 mg/kg to pregnant rats on any of gestation days 6-10, a decreased number of the implantation, an increased number of dead fetuses and fetal growth abnormalities were observed (IARC 21 (1979)). Other than these, there is a report that an increased incidence of cleft palate (12.4% vs 1.1% (control group)) was observed in a test in which pregnant mice were injected subcutaneously at 0.1-0.2 mg/mouse on gestational days 11-16 (IARC 21 (1979)). From the above, since in humans, combination drugs containing this substance have been contraindicated for pregnant women, etc., and in experimental animals, it causes serious reproductive and developmental effects such as pregnancy failure, a decreased conception rate, fetal toxicity, and malformations, it was classified in Category 1A for this hazard class.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Specific target organ toxicity - Repeated exposure	Category 1 (blood coagulation system, nervous system, gallbladder)	Danger	H372	P260 P264 P270 P314 P501	This substance (synonyms: estrone) is one of the estrogens and is used for the treatment of post-menopausal women, etc. (Ethical Pharmaceuticals 2017 (2016), HSDB (Access on August 2017)). In humans, although it is not confined to this substance alone, there is a description that thrombosis or thromboembolism (limbs, lung, heart, brain, retina, etc.) may appear as serious side effects of conjugated estrogen (combination drug of sodium estrone sulfate, sodium equilin sulfate, and sodium 17 alpha-dihydroequilin sulfate) (Ethical Pharmaceuticals 2017 (2016)). In addition, there is a report on the association of hormone replacement therapy (HRT) with a risk of coronary heart disease, stroke, dementia, and gallbladder disease, and it is reported that as for the HRT with a combination drug of conjugated estrogen and progestagen, the risk of the coronary heart disease, stroke, dementia including Alzheimer's, and the gallbladder disease increased significantly, and in the concurrently performed administration of conjugated estrogens to hysterectomized women, the risk of stroke (mainly cerebral infarction) and gallbladder disease was significantly higher, and an increased tendency in the risk of dementia including Alzheimer's was observed (Ethical Pharmaceuticals 2017 (2016)). From the above, since in humans, effects on the nervous system and gallbladder, in addition to thrombosis or thromboembolism, were observed, it was classified in Category 1 (blood coagulation system, nervous system, gallbladder).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
11	Hazardous to the aquatic environment Short term (Acute)	Category 2	- -	H401	P273 P501	From 96-hour LC50 >10 mg/L for crustacea (Neomysis integer) (NLM HSDB:2012, EPA AQUIRE:2017, Ghekiere,A.et al (2006)), it was classified in Category 2.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	If chronic toxicity data are used, then it is classified in Category 1 due to being not rapidly degradable (BioWin), and 40-day NOEC (survival rate) = 0.0000977 mg/L for fish (Danio rerio) (EPA AQUIRE: 2017, Holbech, H. et al. (2006)). Because acute toxicity data were not obtained for a trophic level (algae) for which chronic toxicity data were not obtained, it is classified as "Classification not possible." From the above results, it was classified in Category 1.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

NOTE:

GHS Classification Result by the Japanese Government is intended to provide a reference for preparing a GHS label or SDS for users. To include the same classification result in a label or SDS for Japan is NOT mandatory.
Users can cite or copy this classification result when preparing a GHS label or SDS. Please be aware, however, that the responsibility for a label or SDS prepared by citing or copying this classification result lies with users.
This GHS classification was conducted based on the information sources and the guidance for classification and judgement which are described in the GHS Classification Guidance for the Japanese Government etc. Using other literature, test results etc. as evidence and including different content from this classification result in a label or SDS are allowed.
Hazard statement and precautionary statement will show by hovering the mouse cursor over a code in the column of "Hazard statement" and "Precautionary statement," respectively. In the excel file, both the codes and statements are provided.
A blank or "-" in the column of "Classification" denotes that a classification for the hazard class was not conducted in the year.
An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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