NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	302-17-0
Chemical Name	Chloral hydrate
Substance ID	m-nite-302-17-0_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)	To Workplace Safety Site (MHLW)
Sample SDS by MHLW (External link)	To Workplace Safety Site (MHLW)
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.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
7	Flammable solids	Not classified	- -	-	-	Not combustible (ICSC(J) (1999))	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
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.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
10	Pyrophoric solids	Not classified	- -	-	-	Not combustible (ICSC(J) (1999))	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to solid (melting point <= 140 degC) substances are not available.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
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).	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing chlorine and oxygen which are chemically bonded only to carbon or hydrogen.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
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)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	Based on the rat LD50 value of 480 mg/kg (CICAD 25 (2000)), the substance was classified into Category 4.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Based on the rat LD50 value of 3030 mg/kg (HSDB (2010)), the substance was classified as "Not classified" in the JIS classification (corresponding to Category 5 in the UN-GHS classification).	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	No data available.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	No data available.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
2	Skin corrosion/irritation	Category 1	Danger	H314	P301+P330+P331 P303+P361+P353 P305+P351+P338 P304+P340 P260 P264 P280 P310 P321 P363 P405 P501	The substance was classified as Category 1 since it was described that the substance was corrosive to skin and mucous membrane in human (NTP TR 503 (2002), HSDB (2010)).	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	The substance was classified as Category 1 since it was reported that chloral hydrate is corrosive to the skin and mucous membrane in human (NTP TR 503 (2002), HSDB (2010)), and its preexisting classification concluded as a corrosive substance to skin.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
4	Skin sensitization	Classification not possible	- -	-	-	No data available.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
5	Germ cell mutagenicity	Category 1B	Danger	H340	P308+P313 P201 P202 P280 P405 P501	The classification was concluded as "Category 1B" based on 3 positive results out of 5 micronucleus tests using spermatid obtained after intraperitoneal administration to mice (in vivo mutagenicity test in germ cells) (IARC 84 (2004)). In other mice micronucleus test using bone marrow cells obtained after intraperitoneal administration (in vivo mutagenicity test in somatic cells), 4 positive results out of 6 tests were found (IARC 84 (2004)), and equivocal results of positive and negative data were obtained in the single-strand DNA break test (IARC 84 (2004)). As relevant information, as for in vitro studies, negative or positive results in the Ames test, negative result using Chinese hamster Cl-1 cells and positive result using V79 cells in the micronucleus test, and negative result using Chinese hamster CHED cells and positive result using ovarian cells in the chromosome aberration test (IARC 84 (2004)), were reported.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Information on carcinogenicity in humans is limited to (7). Based on the IARC's classification result (1) and test results of (2)-(6), it was classified in Category 1B. The category was revised as the result of reviewing the previous classification due to the revision of the classification in 2014 by IARC. Besides, NTP regarded the results of (3), (4) as equivocal evidence and some evidence of carcinogenicity respectively and did not classify for carcinogenicity. However, the IARC's evaluation was adopted according to the GHS classification guidance for the Japanese government. [Evidence Data] (1) IARC classified this substance and chloral hydrate in Group 2A by stating that there is sufficient evidence in experimental animals for the substances (IARC 106 (2014)). As for classification results by domestic and international organizations other than this, EPA classified it as CBD (cannot be determined) (IRIS (2010)). (2) In two tests in which male mice were dosed by drinking water for 104 weeks, increased hepatocellular adenoma and carcinoma were observed (IARC 106 (2014)). (3) In a test in which female mice were dosed by gavage for two years, increased incidences of malignant lymphoma and adenoma of the pituitary gland were observed. However, NTP, the organization that conducted the test, did not use malignant lymphoma in evaluation because its incidence was within the historical control range (NTP TR502 (2002), IARC 106 (2014)). (4) In a test in which male mice were dosed by gavage for two years, increased hepatocellular carcinoma was observed (NTP TR503 (2002), IARC 106 (2014)). (5) In a test in which rats were dosed by drinking water for 104 weeks, the incidence of hepatocellular carcinoma in the male low-dose group was higher than that for the historical control (IARC 106 (2014)). (6) As for patters of the absorption, distribution, metabolism and excretion of chloral hydrate in the body, there are major similarities between humans and experimental animals. Besides, strong evidence suggesting that chloral hydrate is genotoxic was obtained (IARC 106 (2014)). [Reference Data, etc.] (7) As for carcinogenicity in humans, in a study in the USA, significant associations were not observed between the number of prescriptions for chloral hydrate and morbidity for cancers (IARC 106 (2014)).	FY2018	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Reproductive toxicity	Not classified	- -	-	-	In the study of mice administered via drinking water, males and females were exposed for 3 weeks prior to mating, and females were consequently continued during the gestation period and until weaning after 21 days of birth, no significant effect on drinking water consumption or weight gain in the dams, as well as on gross external malformations in pups, gestational period and number of pups delivered was observed. Thus, there were no effects except for on several parameters indicating neurobehavioral influence of pups, therefore, it was reported that the NOAEL for reproductive and developmental effects was 204.8 mg/kg/day (the highest dose tested) (IRIS (2000)). In the study, which pregnant rats were administered during the gestation period via drinking water, there was no evidence of maternal toxicity, no change in the number of implantation or resorption sites or no change in the developmental indices such as the number of live or dead fetuses (IRIS (2000)). Based on these results, there were no adverse effects on reproductive functions and fertility of parental animals, and development of offspring. Thus, the substance was classified as the "Not classified". In addition, this substance is known to pass the human placenta at some stage of pregnancy. However, it was reported that its use during pregnancy did not cause detectable increase in abnormal outcomes, even though there were few information. (IARC 84 (2004)).	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, heart), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	It was described that the primary effect on human at ingestion of this substance was depression of central nervous system, the basis of use in therapeutics, and it induced sedation and hypnosis (EHC 216 (2000)). It was reported that acute gavage exposure to mice at doses of 900 mg/kg or lower showed sedation, lethargy and loss of righting reflex, and deaths occurred by respiratory inhibition at 1200 mg/kg or higher (IRIS Toxicological Review (2000)). Based on the information in humans, the substance was classified as Category 1(central nervous system). In addition, the substance is used as a hypnotic drug, and it was reported that in mice study the substance induced clinical signs such as sedation, hypnosis, ataxia (IRIS (2000)). Thus, Category 3 (narcotic effects) was added. Furthermore, it was also described that the most important toxic effect is abnormal cardiac rhythm. It was reported that the induction of arrhythmias in the infant was noted and sinus arrhythmias associated with the substance in two of 12 subjects were also noted (EHC 216 (2000)). Thus, Category 1 (heart) was also added.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
9	Specific target organ toxicity - Repeated exposure	Category 1 (central nervous system), Category 2 (liver)	Danger Warning	H372 H373	P260 P264 P270 P314 P501	As the result of the investigation of medical records for 1618 patients who had received the substance, effects on central nervous system in 20 patients was the most common as the adverse reactions of the substance (IRIS (2000)). In another report reviewed medical records of 5435 hospital patients, adverse reactions were noted in 119 cases and effects on central nervous system in 58 patients was the most common, three of them showed so-called flapping tremor as life-threatening reactions (IRIS (2000)). Based on these, the substance was classified as Category 1 (central nervous system). As for the animal experiments, in the 90-day study via drinking water in rats, focal hepatocellular necrosis was observed in the liver of males at 96 mg/kg/day or more, and necrotic lesion was minimal at 96 mg/kg/day but more severe at 196 mg/kg/day (IRIS (2000)). In addition, the 90-day study via drinking water in mice revealed the findings of hepatomegaly and microsome proliferation in males at 16 mg/kg/day or more. Based on these results, Category 2 (liver) was added since the doses appeared were both within the Category 2 or above category.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）

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)	Not classified	- -	-	-	Classified as "Not classified" from its 48h-EC50 = 500 mg/L for crustacea (Daphnia magna) (HSDB, 2010).	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
11	Hazardous to the aquatic environment Long term (Chronic)	Not classified	- -	-	-	Classified as "Not classified" since its acute toxicity is "Not Classified" and it is not non-water soluble (water solubility = 793000 mg/L (PHYSPROP Database, 2011)).	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in Annexes to the Montreal Protocol.	FY2010	GHS Classification Guidance by the Japanese Government （July, 2010）

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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