NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	127-51-5
Chemical Name	3-Methyl-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one
Substance ID	R02-A-005-METI, MOE
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/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 (FY2019 revised edition (Ver. 2.0))
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 classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
6	Flammable liquids	Not classified	- -	-	-	A flash point was 110.3 deg C ( 968.5 hPa, closed-cup) (ECHA (Accessed June 2020)).
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	There is a chemical group associated with self-reactive properties (ethylene group) present in the molecule, but the classification is not possible due to no data.
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 254 deg C (ECHA (Accessed June 2020)).
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.
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).
13	Oxidizing liquids	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.
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.
17	Desensitized explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LD50 for rats: > 5,000 mg/kg (REACH registration dossier (Accessed May 2020))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LD50 for rabbits: > 5,000 mg/kg (REACH registration dossier (Accessed May 2020))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified."
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (5). [Evidence Data] (1) It is reported that in a patch test in 28 persons (pilot test group 5, full test group 23), after 24-hour occlusive application of 0.5 mL of a 10% solution of this substance (alcohol, w/v), no irritation reactions were found after 24 hours (NICNAS IMAP (2018), REACH registration dossier (Accessed May 2020)). (2) It is reported that in a patch test in 37 persons, no irritation reactions were seen after 24-hour occlusive application of 0.5 mL of 12.5% solution of this substance to the upper arm (NICNAS IMAP (2018), REACH registration dossier (Accessed May 2020)). (3) It is reported that in a patch test in 12 persons, no skin irritation was found after 24-hour occlusive application of 0.3 mL of a 60% solution of this substance (diethyl phthalate: ethanol (3:1)) to the back (REACH registration dossier (Accessed May 2020)). (4) It is reported that in a patch test in 106 persons, an irritation reaction was observed in one person after 9-time 24-hour occlusive applications of 0.3 mL of a 60% solution of this substance (diethyl phthalate: ethanol (3:1)) to the back over 3 weeks (NICNAS IMAP (2018), REACH registration dossier (Accessed May 2020)). (5) It is reported that in a skin irritation test with rabbits (n = 4) (semi-occlusive, 4-hour application, 72-hour observation), there was no skin irritation (mean erythema/eschar score: 1.4, mean edema score: 1.5) (REACH registration dossier (Accessed May 2020)).
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	[Rationale for the Classification] It was classified in Category 2B from (1), (2). [Evidence Data] (1) It is reported that in an eye irritation test with rabbits (n = 3), no corneal opacity or iritis was seen, but conjunctivitis involving chemosis and discharge was observed at 24, 48, and 72 hours after application, and eyes that were applied with this substance became normal after 7 days (corneal opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 2.3/2.3/2.3, chemosis score: 1.7/1.7/1.7) (NICNAS IMAP (2018), REACH registration dossier (Accessed May 2020)). (2) It is reported that in an eye irritation test with rabbits (n = 3), no corneal opacity or iritis was seen in any animal, but conjunctival irritation involving chemosis and discharge was observed at 1-4 days after application, and eyes that were applied with this substance became normal after 7 days (NICNAS IMAP (2018), REACH registration dossier (Accessed May 2020)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1B	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1B from (1) - (5). [Evidence Data] (1) It is reported that after a 10% solution of this substance (petrolatum) was applied to 179 male and female patients suspected of cosmetic allergy for 72 hours in a patch test, positive reactions were seen in two, and the substance was sensitizing to the skin (NICNAS IMAP (2018), REACH registration dossier (Accessed May 2020)). (2) It is reported that in a patch test in 100 persons, after induction by 9-time 24-hour occlusive applications of 0.3 mL of this substance to the left side of the back over 3 weeks followed by challenge by 24-hour application of 0.3 mL of this substance to the right side of the back about 2 weeks later, NOEL = 70,866 microg/cm2 was obtained, and there was skin sensitization (REACH registration dossier (Accessed May 2020)). (3) It is reported that in a patch test in 422 patients with suspected contact allergy, nine showed positive reactions after induction by occlusive application of a 5% solution of this substance (petrolatum) mostly to the face once followed by challenge, and the substance was considered to be sensitizing to the skin (REACH registration dossier (Accessed May 2020)). (4) This substance was listed in list B, one of the fragrance chemicals, which are less frequently reported and thus less documented as consumer allergen (14 substances), but it is reported that there are reports on 10-100 positive cases in humans (SCCS (2012)). (5) It is reported that in a local lymph node assay (LLNA) with mice (OECD TG 429), irritation index (SI) was 0.6 (2.5%), 0.6 (5.0%), 1.5 (10.0%), 3.4 (25.0%), 4.6 (50.0%), the EC3 value was calculated as 21.8%, and slight sensitization was found (NICNAS IMAP (2018), REACH registration dossier (Accessed May 2020)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on the data of (1) to (3), it was classified as "Not classified." [Evidence Data] (1) In a mouse bone marrow micronucleus assay (intraperitoneal injection), negative results were reported (EFSA (2015)). (2) In a bacterial reverse mutation assay, negative results were reported (EFSA (2015)). (3) In the Flavoring Group Evaluation, the EFSA Panel concluded that the concern with respect to genotoxicity could be ruled out for this substance (EFSA (2015)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. In (1), no reproduction toxicity was observed, and in (2), no developmental toxicity was observed. However, in (2), the substance was not administered at the dosage level where toxicity could be developed in maternal animals. Therefore, the test conditions were not regarded as adequate to evaluate developmental toxicity. [Evidence Data] (1) It was reported that in a reproduction/developmental toxicity screening test with rats dosed by gavage (OECD TG421, GLP, for up to 42 days from two weeks prior to pairing (males), from two weeks prior to pairing until day 13 of lactation (females)), no reproduction toxicity was observed at 500 mg/kg/day (REACH registration dossier (Accessed May 2020)). (2) It was reported that in a developmental toxicity study with rats dosed by gavage (gestational days 7 to 17), no developmental toxicity was observed at 30 mg/kg/day (REACH registration dossier (Accessed May 2020), NICNAS IMAP (2018)).
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. In the tests by oral route (1) and (2), it was not known whether the observed effects would appear at doses in the vicinity of the upper limit of Category 2. The effects observed in a dermal application test of (3) were local effects due to dermal irritation. [Evidence Data] (1) It was reported that in a 90-day oral toxicity study with rats dosed by feeding, no treatment-related gross pathological changes were observed at 3.55 mg/kg/day (males, within the range for Category 1) and 4.01 mg/kg/day (females, within the range for Category 1) (approximately 100 times the maximum estimated human dietary levels) (NICNAS IMAP (2018), REACH registration dossier (Accessed May 2020)). (2) It was reported that in a repeated dose 90-day oral toxicity study (OECD TG408, GLP) with rats, centrilobular hepatocyte enlargement (males and females), globular accumulations of eosinophilic material in the renal tubular epithelium (males), follicular cell hypertrophy in the thyroids (males) and adipose infiltration of the bone marrow (males) were observed at 500 mg/kg/day (in the range corresponding to "Not classified") and the NOAEL was determined to be 30 mg/kg/day. It was considered that the effects on the kidneys resulted from the accumulation of alpha 2-microglobulin in proximal tubular epithelial cells and were peculiar to the male rats (NICNAS IMAP (2018), REACH registration dossier (Accessed May 2020)). (3) In a 90-day dermal toxicity study with rats (nonocclusive application), dose-dependent erythema and edema with eschar formation were observed at or above 50 mg/kg/day (within the range for Category 2) in all dosage groups, and this substance was found to be a severe dermal irritant on repeated dermal exposure. It was also reported that at or above 580 mg/kg/day (in the range corresponding to "Not classified"), systemic effects such as reduced body weight gain and decreases in food consumption were reported (NICNAS IMAP (2018), REACH registration dossier (Accessed May 2020)).
10	Aspiration hazard	Classification not possible	- -	-	-	[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)	Category 2	- -	H401	P273 P501	It was classified in Category 2 from 48-hour EC50 = 9 mg/L for crustacea (Daphnia magna) (REACH registration dossier, 2021).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	Reliable chronic toxicity data were not obtained. It was classified in Category 2 because it is not rapidly degradable (BIOWIN), and it was classified in Category 2 in acute toxicity.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.

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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