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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	108-68-9
Chemical Name	3,5-xylenol; 3,5-Dimethylphenol
Substance ID	R01-B-028
Classification year (FY)	FY2019
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised	Revised
Classification result in other fiscal year	FY2008
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)	MHLW Website (in Japanese Only)
Model SDS by MHLW (External link)	MHLW Website (in Japanese Only)
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 a flammable solid, and a flash point is 80-95 deg C for a liquid after melting (Hommel (1991)).
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	*	- -	-	-	Because it is classified in Division 6.1 in UNRTDG (UN2261), and it is considered to be not applicable to pyrophoric solids, hazards of the highest precedence, it was classified as "Not classified."
11	Self-heating substances and mixtures	*	- -	-	-	Classification is not possible because test methods applicable to solid (melting point <= 140 deg C) substances are not 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 oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. It was classified as "Not classified (Not applicable)."
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)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] Based on (1), (2), it was classified in Category 4. [Evidence Data] (1) LD50 for rats: 608 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.15 (Ministry of the Environment, 2017), HSDB (Access on June 2019)) (2) LD50 for rats: 608-3,620 mg/kg (NICNAS IMAP (Access on August 2019))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: > 2,400 mg/kg (ACGIH (7th, 2019))
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] The category could not be specified based on (1) and (2). Therefore, it was classified as "Classification not possible." [Evidence Data] (1) LC50 (7 hours) for rats: > 0.7 mg/L (converted 4-hour equivalent value: > 1.2 mg/L) (NICNAS IMAP (Access on August 2019)) (2) LC0 (7 hours) for rats: saturated concentration (0.13 mg/L) (converted 4-hour equivalent value: 0.23 mg/L) (ACGIH (7th, 2019))
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	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1. [Evidence Data] (1) Moderate burns to the skin were reported in rabbits after administration to the skin (concentration not specified) (NICNAS IMAP (Access on August 2019)). (2) It was classified in "Skin Corr. 1B (H314)" in EU-CLP classification (EU CLP classification (Access on May 2019)). [Reference Data, etc.] (3) In a 24-hour occlusive skin irritation study with rabbits (Polyethylene glycol (PEG) 400 was used as vehicle), slight edema was observed in half of the animals at 24 hours after application and disappeared after 72 hours. PII was 0.25 (ACGIH (7th, 2019), (REACH registration dossier (Access on July 2019))).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 1. [Evidence Data] (1) In an eye irritation test in which this substance (100 mg) was administered to the eyes of rabbits, corneal opacity, reduced response to light, injection, reddening and chemosis, and ocular discharge were observed, and no recovery was observed during the observation period (7 days). The mean irritation score of 24/48/72 hours was 58.5/110, and it was classified as highly irritating (ACGIH (7th, 2019), REACH registration dossier (Access on July 2019)). (2) In a study with rabbits administered either undiluted or dilution of this substance in propylene glycol, in the undiluted treated eyes, extreme conjunctivitis with moderate corneal injury and iritis was observed (ACGIH (7th, 2019)). (3) Eye irritation studies in rabbits reported permanent eye damage (NICNAS IMAP (Access on August 2019)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	*	- -	-	-	[Rationale for the Classification] Although data shown in (1) and (2) exist, both positive and negative results were reported, therefore, it was classified as "Classification not possible." [Reference Data, etc.] (1) In a guinea pig skin sensitization test according to OECD TG 406 (maximization method, intradermal induction: 1%, induction (topical application): 5%, challenge: 0.5%), the same skin reactions were observed in both test and control groups, and the results were judged as inconclusive or negative (REACH registration dossier (Access on July 2019), NICNAS IMAP (Access on August 2019)). (2) From the results of guinea pig studies and in a mouse local lymph node assay (LLNA) for dimethylphenols, they, including this substance, are considered to be potential skin sensitizers (ACGIH (7th, 2019)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not Classified." Because negative findings were observed in all the standard combination tests, including in vivo and in vitro tests. [Evidence Data] (1) As for in vivo, a negative result was reported for a mouse erythrocyte micronucleus test (ACGIH (7th, 2019), NICNAS IMAP (Access on August 2019), Environmental Risk Assessment for Chemical Substances Vol.15 (Ministry of the Environment, 2017)). (2) As for in vitro, negative results were reported for a bacterial reverse mutation test and a chromosomal aberration test in rat hepatocytes (ACGIH (7th, 2019), NTP DB (Access on June 2019), Environmental Risk Assessment for Chemical Substances Vol.15 (Ministry of the Environment, 2017)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on classification results by other organizations in (1) and the report of (2), it was classified in Category 2. Since new data were obtained, the category was changed from the previous classification. [Evidence Data] (1) In the classification results by domestic and international organizations, it was classified in A3 by ACGIH (ACGIH (7th, 2019)). (2) In a test in which this substance was dermally applied to mice for 28 weeks, it is reported to be carcinogenic to the skin (ACGIH (7th, 2019)).
7	Reproductive toxicity	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) In a combined oral repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422) with rats by oral gavage of a mixture of six dimethylphenol (xylenol) isomers, including this substance, although increases in relative weights of the kidney, liver and ovaries were observed as general toxicity, no apparent reproductive effects were observed (ACGIH (7th, 2019), NICNAS IMAP (Access on August 2019)).
8	Specific target organ toxicity - Single exposure	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) There is one case report of an individual who ingested 250 mL of a disinfectant product that was reported as a mixture of six isomeric dimethylphenols (xylenol) including this substance, in an alcoholic, anionic base. The individual exhibited gastrointestinal effects (active bowel sounds, nausea and vomiting) and central nervous system depression (barely rousable) that progressed to metabolic acidosis and heart and cardiovascular changes (hypotension with reduced cardiac output), and then death about 16 hours following the ingestion. The lethal dosage of dimethylphenol (xylenol) ingestion in this case report was not reported (ACGIH (7th, 2019)). (2) In a single oral dose study with rats, although signs of central nervous system effects were reported at 1,000 mg/kg (correspond to Category 2) and above for this substance was observed, these were considered to be due to severe irritation of the gastrointestinal tract (ACGIH (7th, 2019)). (3) In experimental animals, it is reported that sublethal signs of toxicity for xylenol compounds, including this substance, included dyspnea, loss of motor coordination and spasms, but the details are not available (NICNAS IMAP (Access on August 2019)).
9	Specific target organ toxicity - Repeated exposure	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) As a result of oral administration of 3,4-Dimethylphenol (3,4-xylenol) (CAS RN 95-65-8) for 8 months to rats, decreased body weight and effects on blood pressure, the liver, spleen, heart and lungs are reported at 14 mg/kg/day (within the range of Category 2), however, as these effects have not been replicated in more recent studies conducted at higher dosages, these findings are not considered reliable (ACGIH (7th, 2019)). (2) Regarding dimethylphenol (xylenol), ACGIH considers that the 6 isomers and the mixed isomer substance are similar in toxicity, and sets a common TLV after conversion to an inhalation exposure based on the toxicity information of 2,4-dimethylphenol (2,4-xylenol) (CAS RN 105-67-9) (NOAEL based on changes in hematological parameters observed in a 90-day oral dose study with mice at 250 mg/kg/day (exceeding the range of Category 2) = 50 mg/kg/day) (ACGIH (7th, 2019)).
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)	Category 3	- -	H402	P273 P501	It was classified in Category 3 from 24-hour EC50 = 22 mg/L for crustacea (Daphnia magna) (ECETOC TR91, 2003, Environmental Risk Assessment for Chemical Substances Vol. 15 (Ministry of the Environment, 2017)), and 96-hour LC50 = 22 mg/L for fish (Carassius auratus) (Environmental Risk Assessment for Chemical Substances Vol. 15 (Ministry of the Environment, 2017)).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 3	- -	H412	P273 P501	If chronic toxicity data are used, then it is classified as "Not classified" due to being not rapidly degradable (a degradation rate by BOD: 0% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 2012)), and 72-hour NOEC = 50 mg/L for algae (Chlorella pyrenoidosa) (Environmental Risk Assessment for Chemical Substances Vol. 15 (Ministry of the Environment, 2017)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 3 due to being not rapidly degradable (a degradation rate by BOD: 0% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 2012)), 24-hour EC50 = 22 mg/L for crustacea (Daphnia magna) (ECETOC TR91, 2003, Environmental Risk Assessment for Chemical Substances Vol. 15 (Ministry of the Environment, 2017)), and 96-hour LC50 = 22 mg/L for fish (Carassius auratus) (Environmental Risk Assessment for Chemical Substances Vol. 15 (Ministry of the Environment, 2017)). By drawing a comparison between the above results, it was classified in Category 3.
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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