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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	302-22-7
Chemical Name	Chlormadinone acetate
Substance ID	H29-A-015
Classification year (FY)	FY2017
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised	New
Classification result in other fiscal year
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
UN GHS document (External link)	UN GHS document
Definitions/Abbreviations (Excel file)	Definitions/Abbreviations
Model Label by MHLW (External link)
Model SDS by MHLW (External link)
OECD/eChemPortal (External link)	eChemPortal

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Explosives	Not applicable	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases (including chemically unstable gases)	Not applicable	- -	-	-	Solid (GHS definition).
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Solid (GHS definition).
5	Gases under pressure	Not applicable	- -	-	-	Solid (GHS definition).
6	Flammable liquids	Not applicable	- -	-	-	Solid (GHS definition).
7	Flammable solids	Classification not possible	- -	-	-	No data available.
8	Self-reactive substances and mixtures	Not applicable	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9	Pyrophoric liquids	Not applicable	- -	-	-	Solid (GHS definition).
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data available.
12	Substances and mixtures which, in contact with water, emit flammable gases	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).
13	Oxidizing liquids	Not applicable	- -	-	-	Solid (GHS definition).
14	Oxidizing solids	Not applicable	- -	-	-	The substance is an organic compound containing oxygen and chlorine (but not fluorine) which are chemically bonded only to carbon.
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances are not available.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Not classified	- -	-	-	Based on a report of an LD50 value of 6,400 mg/kg for rats (HSDB (Access on August 2017)), it was classified as "Not classified."
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
2	Skin corrosion/irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data.
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data.
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	As for in vivo, there are reports that a chromosomal aberration test and a sister chromatid exchange test with mouse bone marrow cells, and a micronucleus test with rat liver were positive (HSDB (Access on August 2017) (EMEA/MRL/649/99 (2000))). As for in vitro, there are reports that bacterial reverse mutation tests were negative (EMEA/MRL/649/99 (2000)), and that a chromosomal aberration test and a sister chromatid exchange test with human cultured lymphocytes were positive (HSDB (Access on August 2017)). From the above, it was classified in Category 2 according to the GHS classification guidance for the Japanese government.
6	Carcinogenicity	Classification not possible	- -	-	-	There is no report on carcinogenicity by administration of this substance alone in humans (IARC 21 (1979), IARC Suppl. 7 (1984), EMEA/MRL/649/99 (2000)). As for experimental animals, in tests in which this substance was administered by feeding to rats and mice (mammary tumor virus negative) at up to the doses of 200-400 times (2-4 mg/kg/day) the clinical dose for 104 weeks in rats and for 80 weeks in mice, no increase in tumor incidence was observed (IARC 21 (1979), EMEA/MRL/649/99 (2000)). In addition, in a test in which mammary tumor virus positive (MTV+) mice were dosed by feeding at 0.6-0.8 mg/kg, delayed onset of mammary gland tumors was shown in females (IARC 21 (1979), EMEA/MRL/649/99 (2000)). From the above, no carcinogenicity due to administration of this substance was observed in the rats or mice. However, as a result of administration of 0.25 mg/kg/day (25 times of the clinical dose) of this substance to dogs for 104 weeks, small nodules in the mammary glands were observed in 6 out of 20 females, and similar small nodules were observed in 4 cases in the control group. However, it was confirmed that those in the control group were not abnormal proliferation of the mammary tissue histologically. A slightly larger nodule was observed in another one in the treated group, and it was confirmed to be a histologically benign tumor (IARC 21 (1979), EMEA/MRL/649/99 (2000)). Moreover, as a result of a histological examination of 22 nodules which appeared in the mammary gland site 4 years after administration of this substance to 14 female dogs, 12 points among them were nodular hyperplasia, 4 points were combined benign tumors, one point was an adenocarcinoma, and the remaining 5 points contained no mammary tissue (IARC 21 (1979), EMEA/MRL/649/99 (2000)). Although IARC concluded that there is limited evidence for carcinogenicity in animals (dogs) (IARC 21 (1979), IARC Suppl. 7 (1984)), it did not classify this substance for carcinogenicity (IARC Suppl. 7 (1984)). From the above, in experimental animals, it is concluded that there is only limited evidence in dogs, and there is no clear evidence of carcinogenicity in other animal species. There are also no classification results by other organizations, therefore, it was classified as "Classification not possible."
7	Reproductive toxicity	Category 1A	Danger	H360	P308+P313 P201 P202 P280 P405 P501	This substance is used as a therapeutic agent for prostate hypertrophy and prostate cancer, and there are reports of impotence, female type breasts etc. as side effects (Ethical Pharmaceuticals 2017 (2016)). As for experimental animals, there are the following reports: as a result of dosing pregnant mice by gavage (1-50 mg/kg/day, gestational day 8-15 or 14-17), malformations such as cleft palate were observed, and fetal deaths and embryo/fetal resorptions frequently occurred at or above 10 mg/kg/day; as a result of dosing pregnant rabbits (1-10 mg/kg/day, gestational day 8-20), occurrence of malformations and deaths were frequently observed at 10 mg/kg/day in fetuses; as the results of administration of high doses of this substance (pigs: 60 mg/animal, dogs: 1 mg/animal) for 14-18 days to pigs, and 21 days to dogs, a reversible decrease in libido was seen in both sexes of both species; and as a result of administration to cows at up to 8 times the clinical dose for up to 3 months, dose-dependent reversible infertility was observed (IARC 21 (1979), EMEA/MRL/694/99 (2000)). From the above, impotence is reported as a side effect in humans, and even for experimental animals, there are reports on reproductive and developmental effects such as teratogenicity, therefore, it was classified in Category 1A.
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	Classification not possible due to lack of data.
9	Specific target organ toxicity - Repeated exposure	Category 1 (blood coagulation system, cardiovascular system, liver, endocrine system)	Danger	H372	P260 P264 P270 P314 P501	This substance is corpus luteum hormone and used as a therapeutic agent for amenorrhea, menstrual cycle abnormality, ovarian dysfunction, infertility due to corpus luteum dysfunction, prostate hypertrophy and prostate cancer (Ethical Pharmaceuticals 2017 (2016)). For the treatment of amenorrhea and so on, there were reports that side effects were observed in 2 out of 19 cases. For the treatment of prostate hypertrophy, in 25 mg tablets, side effects were reported in 154 (2.3%) out of 6,809 cases, and the main effects were impotence (1.1%), gastrointestinal tract disorder (0.4%), damage of the liver and bile duct (0.2%), etc., and in 50 mg tablets, side effects were reported in 199 (5.52%) out of 3,607 survey cases, the main effects were impotence (2.33%), decreased libido (0.69%), anemia (0.47%), etc. For the treatment of prostate cancer, side effects were reported in 84 (8.4%) out of 996 cases, and main effects were gynecomastia (3.0%), damage of the liver and bile duct (1.5%), edema (1.3%), etc. In addition, it is described that as serious side effects (incidence less than 0.1% or unknown), congestive heart failure, thrombosis, fulminant hepatitis, liver dysfunction, jaundice, diabetes, etc. may appear (Ethical Pharmaceuticals 2017 (2016)). Of the above, the impotence and gynecomastia were considered as effects on the endocrine system. Also, gastrointestinal tract disorder was judged to be insufficient as the evidence for GHS classification because it is stomach discomfort and so on. Therefore, it was classified as Category 1 (blood coagulation system, cardiovascular system, liver, endocrine system).
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
11	Hazardous to the aquatic environment (Acute)	Classification not possible	- -	-	-	No data available.
11	Hazardous to the aquatic environment (Long-term)	Classification not possible	- -	-	-	No data available.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.

NOTE:

* A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted.
* Hazard_statement_and/or_Precautionary_statement will show when hovering the mouse over a code of Hazard_statement_and/or_Precautionary_statement.
Hazard_statement_and/or_Precautionary_statement are also provided in the Excel file.
* Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government,
and is intended to provide a reference for preparing GHS labelling and SDS for users.
* This is a provisional English translation of classification results and is subject to revision without notice.
* The responsibility for any resulting GHS labelling and SDS referenced from this site is with users.
* Codes assigned to each of the hazard statements and codes for each of the precautionary statement are
based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations.

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