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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	98-73-7
Chemical Name	p-tert-Butylbenzoic acid
Substance ID	R03-B-001-MHLW
Classification year (FY)	FY2021
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)
New/Revised	Revised
Classification result in other fiscal year	FY2013 FY2010
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)	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	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
7	Flammable solids	Classification not possible	- -	-	-	No data available.Besides, there is information that it is combustible (GESTIS (Accessed Oct. 2021)).
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.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
10	Pyrophoric solids	Not classified	- -	-	-	It is considered that it does not ignite at normal temperatures because it is estimated that it does not decompose up to 280 deg C from the information that it decomposes at > 280 deg C.
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 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)	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	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.
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	- -	-	-	Test methods applicable to solid substances are not 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)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] Based on (1) to (6), it was classified in Category 4. [Evidence Data] (1) LD50 for rats: 473 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), ACGIH (2020)) (2) LD50 for rats (females): 642 mg/kg (ACGIH (2020)) (3) LD50 for rats (females): < 720 mg/kg (CLH Report (2010), EU RAR (2009)) (4) LD50 for rats (males): 720 mg/kg (CLH Report (2010), EU RAR (2009)) (5) LD50 for rats: 735 mg/kg (CLH Report (2010), EU RAR (2009), ACGIH (2020)) (6) LD50 for rats (females): between 550 to 800 mg/kg (CLH Report (2010), EU RAR (2009), ACGIH (2020))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Also, since (2) and (3) presented the data for a 30% solution in DMSO, they were not adopted as evidence data. Based on the new findings, the classification was changed from the previous classification. [Evidence Data] (1) LD50 for rabbits: > 2,000 mg/kg (EU RAR (2009), AICIS IMAP (2013), ACGIH (2020)) [Reference Data, etc.] (2) LD50 for rabbits: > 900 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), EU RAR (2009), AICIS IMAP (2013), ACGIH (2020)) (3) LD50 for rats: 300 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), EU RAR (2009))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Solid (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] Based on (1) and (2), it was not classified in Categories 1 to 3, but no category could be identified. Therefore, the classification was not possible due to lack of data. [Evidence Data] (1) LC50 (dust, 4 hours) for rats: > 1.8 mg/L (EU RAR (2009), AICIS IMAP (2013), ACGIH (2020), REACH registration dossier (Accessed Oct. 2021)) (2) LC50 (dust, 4 hours) for rats:> 1.9 mg/L (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), ACGIH (2020))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in a skin irritation test with rabbits (n=6) (GLP, semiocclusive, 4-hour application, observation for 72 hours), no skin reactions were observed (EU RAR (2009), AICIS IMAP (2013), REACH registration dossier (Accessed Oct. 2021)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Besides, the data were reviewed, and the classification was changed from the previous classification. [Evidence Data] (1) It was reported that, in an eye irritation test with rabbits (n=6) (GLP, observation for 72 hours), slight conjunctival redness was observed in all animals after 24 hours but all reactions completely resolved after 72 hours (after 24/48/72 hours, mean corneal opacity score: 0.3, mean iritis score: 0, mean conjunctival redness score: 0.5, mean chemosis score: 0.1) (EU RAR (2009), AICIS IMAP (2013), REACH registration dossier (Accessed Oct. 2021)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) In a Maximization test with guinea pigs (n=10) (OECD TG406, GLP, intradermal injection: 25% solution), all animals showed no skin reactions after the challenge treatment (EU RAR (2009), AICIS IMAP (2013), ACGIH (8th, 2020), REACH registration dossier (Accessed Oct. 2021)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) As for in vivo, a mammalian bone marrow chromosomal aberration test with rats (OECD TG475, single oral dose) was negative (EU RAR (2009), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), ACGIH (8th, 2020), AICIS IMAP (2013), REACH registration dossier (Accessed Sep. 2021)). (2) As for in vitro, negative results were obtained in a bacterial reverse mutation assay, and weakly positive (+S9) and negative (-S9) results were obtained in a micronucleus test with the cultured mammalian cells (Chinese hamster V79 cells) (EU RAR (2009), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), ACGIH (8th, 2020), AICIS IMAP (2013), REACH registration dossier (Accessed Sep. 2021), Mutagenicity Test Data of Existing Chemical Substances based on the toxicity investigation system of the Industrial Safety and Health Law (Accessed Sep. 2021)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), it was classified in 1B since, at a high dose (41 mg/kg/day) at which reduced body weight gain was observed, male sterility attributed to testicular toxicity was observed in all animals, and even at a dose at which no reduced body weight gain was observed (7.9 mg/kg/day), loss of fertility was observed in 1 of 10 animals. [Evidence Data] (1) In a reproduction toxicity study with male rats dosed by feeding (0.002 to 0.05% (converted guidance value: 1.6 to 41 mg/kg/day), mated with untreated females after 70-day treatment), reduced body weight gain was observed in the group dosed at 0.05% (converted guidance value: 41 mg/kg/day) during the treatment period, but there was no description about other general toxicity effects. As a result of being mated with untreated females, 1 of 10 male rats in the group dosed at 0.01% (converted guidance value: 7.9 mg/kg/day) and all male rats (10/10 animals) in the 0.05% group did not succeed in impregnating the female rats and a marked decrease in fertility was observed. The group of males dosed at 0.05% were kept for 70 days without exposure to this substance (with feeding of usual diet) and then mated with untreated females again. As a result, recovery of fertility was observed. At the end of the test, testes weight of the 0.05% group decreased to 88% of that of the 0.01% group, and minor lesions in the germinal epithelium of the seminiferous tubules were found in 7 of 10 animals (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), ACGIH (8th, 2020), AICIS IMAP (2013), CLH Report (2010), ECHA RAC (Background Doc.) (2011), EU RAR (2009), REACH registration dossier (Accessed Oct. 2021)). (2) In repeated dose toxicity studies in the oral and dermal routes with rats, testicular toxicity was observed, and the testis is one of target organs for this substance (See the item for Specific Target Organ Toxicity (Repeated exposure)). [Reference Data, etc.] (3) Effects on the testicular function were investigated with 90 male workers exposed to this substance at a chemical factory in the U.S. with a control group of male workers with no history of exposure to chemical substances that were considered to have testicular toxicity. As a result, no effects on the testicular function were observed and there was no evidence that the exposure to this substance caused infertility. Subsequently, a reevaluation study was conducted with an increased number of controls, and no effects on the testicular function were observed (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), ACGIH (8th, 2020)). (4) In the EU CLP classification (Accessed Sep. 2021), it was classified as Repr. 1B.
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system, testis)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1 (nervous system, testis). [Evidence Data] (1) It was reported that, in an acute oral toxicity test with rats and mice, the LD50 was in the range of 550 to 880 mg/kg, and at doses near or below the lethal dose, hypoactivity, ataxia, hypothermia to the touch, absence of pain reflex, yellow-stained abdomen and anal area, impaired use of front limbs, and hypospermatogenesis of the testes were observed, and in rats, convulsions followed by side lying, tremors, and testicular atrophy were observed (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), AICIS IMAP (2013), EU RAR (2009), CLH Report (2010), ACGIH (2020)). (2) It was reported that, in an acute inhalation exposure test with rats (4 hours), effects on the testes and spinal cord were observed at 0.495 mg/L (within the range for Category 1). Besides, it was also reported that the effects on the testes were caused by decreased sperm counts, etc. and that the forelimb neuropathy was found to be caused by multifocal and multiple myelopathy by microscopy (EU RAR (2009), AICIS IMAP (2013), ACGIH (2020)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, kidney, male reproductive organs)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] In (1), the human data did not show any effects, but in (2) to (4), effects on the nervous system, kidneys, and male reproductive systems were observed in animals. Therefore, it was classified in Category 1 (nervous system, kidney, male reproductive systems). Besides, the liver and the blood system identified as target organs in the previous classification were not adopted for this classification because the substance used in the evidence data was a mixture. [Evidence Data] (1) It was reported that effects on the testicular function were investigated with 90 male workers exposed to this substance at a chemical factory in the U.S. and no effects on the testicular function were observed. In addition, it was reported that there were no effects on the liver and kidney functions or production of red blood cells (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), ACGIH (2020)). (2) It was reported that, in a repeated dose 90-day oral administration study with rats dosed by feeding, increased relative liver weight, renal tubular necrosis and renal papillary necrosis, and atrophy of the testes caused by degenerated epithelium of seminiferous tubules (males) were observed at or above 100 ppm (6 mg/kg/day (males), 8 mg/kg/day (females), within the range for Category 1); increased relative kidney weight (males), decreased relative testis weight (males), and reduced body weight gain (males) were observed at or above 316 ppm (21 mg/kg/day (males), 27 mg/kg/day (females), within the range for Category 2); and an increase in serum urea nitrogen and reduced body weight gain (females) were observed at 10,000 ppm (75 mg/kg/day (males), 89 mg/kg/day (females), in the range corresponding to "Not classified"). It was reported that death or sacrifice in extremis (8 of 10 animals (males), 3 of 10 animals (females)) was observed at 316 ppm (15.8 mg/kg/day, within the range for Category 2) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), ACGIH (2020), EU RAR (2009), AICIS IMAP (2013), CLH Report (2010)). (3) It was reported that, in a 28-day repeated dermal administration test with rats, decreases in absolute and relative testes weight (males) and degeneration of the germinal epithelium in the testes (males) were observed at 60 mg/kg/day (converted guidance value: 18.7 mg/kg/day, within the range for Category 1) (EU RAR (2009), AICIS IMAP (2013), CLH Report (2010), ACGIH (2020)). (4) It was reported that, in a 28-day repeated inhalation exposure test with rats (dust, 6 hours/day, 5 days/week), an increase in the number of animals with decreased arousal (males) and urinating/defecating while in the arena (males) was observed at 0.0047 mg/L (converted guidance value: 0.00104 mg/L, within the range for Category 1), and a decrease in activity (males), a decrease in rearing counts (males), an increase in the incidence of body tremor (males), increased facial staining and hair loss (males), and an increase in liver weight (females) were observed at 0.0157 mg/L (converted guidance value: 0.00349 mg/L, within the range for Category 1) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2021), ACGIH (2020), EU RAR (2009), AICIS IMAP (2013), CLH Report (2010)).
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)	-	- -	-	-	-
11	Hazardous to the aquatic environment Long term (Chronic)	-	- -	-	-	-
12	Hazardous to the ozone layer	-	- -	-	-	-

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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