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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	3327-22-8
Chemical Name	3-Chloro-2-hydroxyprop-1-yl(trimethyl)aminium chlorode
Substance ID	R01-A-009
Classification year (FY)	FY2019
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	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2	Flammable gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
7	Flammable solids	*	- -	-	-	No data available. Besides, there is information that it is combustible (GESTIS (Access on June 2019)).
8	Self-reactive substances and mixtures	*	- -	-	-	There are no chemical groups associated with explosive or self-reactive properties present in the molecule. It was classified as "Not classified (Not applicable)."
9	Pyrophoric liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
10	Pyrophoric solids	*	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from information that there was no self-heating when the temperature was increased to 400 deg C (EU-RAR (2008)).
11	Self-heating substances and mixtures	*	- -	-	-	No data available.
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). It was classified as "Not classified (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	The substance is an organic compound containing one oxygen atom and two chlorine atoms (but not fluorine), and the oxygen and one chlorine atom are chemically bonded only to carbon or hydrogen. The other chlorine atom is ionically bonded and does not contribute to oxidization. From the above, it was classified as "Not classified."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	*	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: male: 4.15 mL/kg (4,810 mg/kg), female: 4.05 mL/kg (4,700 mg/kg) (60%) (converted value as pure substance: approx. 2,800 mg/kg) (EU-RAR (2008)) (2) LD50 for rats: approx. 2,170 mg/kg (EU-RAR (2008)) (3) LD50 for rats: 2,213 mg/kg (EU-RAR (2008))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (EU-RAR (2008)) [Reference Data, etc.] (2) LD50 for rats: > 2,348 mg/kg (65%) (converted value as pure substance: > 1,526 mg/kg) (EU-RAR (2008))
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) Inhalation test (7 hours) with rats: no death at 12.05 mg/L (converted 4-hour equivalent value: 21.09 mg/L) (EU-RAR (2008))
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) In a skin irritation test in which 580 mg of this substance was applied semi-occlusively to intact or abraded skin of rabbits for 4 hours, the scores at 30 minutes, 24, 48 and 72 hours after patch removal were all 0 (EU-RAR (2008)). (2) In a skin irritation test by a 24-hour occlusive application of 0.5 mL of this substance to rabbit skin, the scores at 24 and 72 hours after the removal of a patch were all 0. Besides, half of the animals were scarred in the application skin (EU-RAR (2008)). (3) A skin irritation test by a 24-hour occlusive application with 55% solution of this substance caused very slight skin irritation in 2/6 rabbits with the intact skin and 2/6 rabbits with the abraded skin. The effects disappeared after 72 hours. Besides, half of the animals were tested with the abraded skin (EU-RAR (2008)).
3	Serious eye damage/eye irritation	*	- -	-	-	[Rationale for the Classification] Based on (1)-(5), it was classified as "Not classified." [Evidence Data] (1) In an eye irritation test in which 116 mg of this substance was applied to one eye in rabbits, and then examined at 24,48,72 hours and 7 days after the instillation, all the scores were 0 after 24 and 48 hours, except in one animal that had a redness score of 1 (EU-RAR (2008)). (2) In an eye irritation test with rabbits, the result showed slight initial erythema, edema and hypersecretion of the conjunctiva during the initial hours, but no effect was seen in the cornea or the iris. The conjunctival reaction disappeared after 24 hours (EU-RAR (2008)). (3) In an eye irritation test after application of a 65% solution of this substance to the eyes of rabbits, and then examined after 1, 24, 48, 72, 96 hours and 7 days, the mean scores for conjunctival redness and edema at 24/48/72 hours were 1.7 and 1 in all 3 animals and only 1 animal showed 0.3 in the cornea. All the others were 0 (EU-RAR (2008)). (4) In an eye irritation test in which after instillation of a 60% solution of this substance to the eyes of rabbits, and then examined after 1, 24, 48, 72, 96 hours and 7 days, the mean score for conjunctival redness at 24/48/72 hours was 2 in 2/3 animals, however, the mean score was 0.7-1.7 for edema and 0 for the cornea and iris (EU-RAR (2008)). (5) A 65% aqueous solution of this substance shows mild eye irritation in humans (SIAP (2008)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	*	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) In a skin sensitization test with guinea pigs according to OECD TG 406 (Buehler method, 0.5 mL, 6-hour occlusive application, once/week for three weeks), slight erythema was observed in 2/10 animals, however, this was considered as not sufficient to warrant classification as a skin sensitizer (EU-RAR (2008)). (2) In a skin sensitization test with guinea pigs according to OECD TG 406 (maximization method, intradermal induction: 0.5%, induction (topical application): undiluted test substance, challenge: 30%), the result was determined to be negative (EU-RAR (2008)). (3) This substance is not irritating and not sensitizing to humans (SIAP (2008)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1), although a mouse micronucleus test was negative, all in vitro tests examined in (2) showed positive results, and data are insufficient to evaluate effects in vivo, therefore, the classification was not possible due to lack of data. [Evidence Data] (1) As for in vivo, a negative result was reported in a micronucleus test by intraperitoneal administration to mice (EU-RAR (2008)). (2) As for in vitro, positive results were reported in bacterial reverse mutation tests, a chromosomal aberration test with human lymphocytes and a mammalian cell gene mutation test (HGPRT) (EU-RAR (2008)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified as Carc.2 in EU CLP (EU CLP classification (Access on June 2019)). In the EU, it is considered that this substance is not a local carcinogen when administered via the skin, but there is a possibility that it is a systemic carcinogen based on the increased incidence of bronchiolo-alveolar tumors. However, because there is not enough information on the mutagenicity in vivo, it is impossible to rule out the possibility that this substance is a carcinogen without a threshold (EU-RAR (2008)). (2) In a dermal application test of this substance (13.8 or 138 mg/animal) to mice, twice a week for 105 weeks with males and for 89 weeks with females, an increased incidence of bronchio-alveolar adenomas and/or carcinomas (combined) was observed in the high dose group in both sexes (a significant difference in males, and no significant difference but increasing trend in females). Besides, no tumors were observed at the site of application (EU-RAR (2008), REACH registration dossier (Access on June 2019)).
7	Reproductive toxicity	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
8	Specific target organ toxicity - Single exposure	Category 3 (Narcotic effects)	Warning	H336	P304+P340 P403+P233 P261 P271 P312 P405 P501	[Rationale for the Classification] There is no report on single exposure to this substance in humans. As for experimental animals, based on (1) and (2), abnormal gait, lethargy and ataxia were observed at doses corresponding to Category 2, it was classified in Category 3 (narcotic effects). [Evidence Data] (1) As a result of a single oral dose to rats, mortality (males: 1/5 animals, females: 0/5 animals), abnormal gait, lethargy, decreased respiratory rate, pallor of the extremities and increased salivation were observed at 1,600 mg/kg (corresponding to Category 2). Autopsy revealed congestion or hemorrhage of the lungs and pallor of the liver, spleen and kidneys (EU-RAR (2008)). (2) As a result of single oral administration of a 60% solution of this substance to rats, sedation, ataxia and exophthalmus were observed at doses corresponding to Category 2 (converted value equivalent to pure substance: 1,152-1,986 mg/kg) (EU-RAR (2008)).
9	Specific target organ toxicity - Repeated exposure	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) In a 28-day administration test in which rats were given the test substance by gavage (this substance: 69.57%, water: 28.44%, 1,3-bis-trimethylammonium propanol-2-dichloride: 1.14%, 2,3-dihydroxypropyl-trimethylammonium chloride: 0.63%), slight or moderate vacuolisation of the proximal tubule cells in males, and minimal tubular hyperplasia and minimal or slight hypertrophy in males and females were observed at 1,085 mg/kg/day (converted guidance value: 338 mg/kg/day (converted value equivalent to this substance: 236 mg/kg/day), above the range for Category 2) (EU-RAR (2008)). Since this test was conducted with only one dose, the effects at lower doses are unknown. (2) In a chronic toxicity test in which the test substance (this substance: 65.79%, water: 32.36%, unknown content: 1.85%) was applied to mice dermally 2 times/week (for 105 weeks to males and 89 weeks to females), minimal to mild focal acanthosis and hyperkeratosis at the application site at or above 0.018 mL/animal/dose (575 mg/kg/week), and increased absolute and relative weight of the liver and adrenal gland, and increased absolute weight of the right kidney in females at 0.18 mL/animal/dose (5,750 mg/kg/week), were observed (EU-RAR (2008)).
10	Aspiration hazard	*	- -	-	-	[Rationale for the Classification] 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 Short term (Acute)	Not classified	- -	-	-	It was classified as "Not classified" from 72-hour ErC50 > 10,000 mg/L for algae (Desmodesmus subspicatus), 48-hour EC50 = 164 mg/L for crustacea (Daphnia magna), and 96-hour LC50 = 4,128 mg/L for fish (Danio rerio) (all, SIAP, 2008, EU-RAR, 2008).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	If chronic toxicity data are used, then it is classified in Category 2 due to being not rapidly degradable (BIOWIN), and 21-day NOEC = 0.51 mg/L for crustacea (Daphnia magna) (SIAP, 2008, EU-RAR, 2008). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified as "Not classified" due to no bioaccumulation measured (log Kow < -1.5 (EU-RAR, 2008)), 72-hour ErC50 > 10,000 mg/L for algae (Desmodesmus subspicatus), and 96-hour LC50 = 4,128 mg/L for fish (Danio rerio) (both, SIAP, 2008, EU-RAR, 2008), although it is not rapidly degradable (BIOWIN). By drawing a comparison between the above results, it was classified in Category 2.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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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