NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	98-54-4
Chemical Name	4-tert-Butylphenol
Substance ID	m-nite-98-54-4_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.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Flammable solids	Classification not possible	- -	-	-	It is combustible, but the classification is not possible due to no data.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Pyrophoric solids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 510 deg C (EU-RAR (2008)).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to solid (melting point <= 140 deg C) substances are not available.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances are not available.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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)	Not classified	- -	-	-	There are 10 reports of LD50 values for rats within the ranges of 801-5,660 mg/kg and > 2,000 mg/kg. Three reports correspond to Category 4 and 7 reports correspond to "Not classified" (4 of them correspond to "Not classified" (Category 5 in the UN GHS classification): 2,990 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008), DFGOT Vol. 11 (1998)), 3,500 mg/kg, 4,000 mg/kg (EU-RAR (2008)), and 3,620 mg/kg (females) (EU-RAR (2008), Hazard Assessment Report (CERI, NITE, 2007))). Therefore, this substance was classified as "Not classified" (Category 5 in the UN GHS classification) to which the greatest number of reports (4) corresponded.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	There are five reports of LD50 values for rabbits: 1,580 mg/kg (PATTY (6th, 2012)), > 2,000 mg/kg (EU-RAR (2008)), 2,318 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008), DFGOT Vol. 11 (1998)), > 5,000 mg/kg (DFGOT Vol. 11 (1998)), and > 16,000 mg/kg (Hazard Assessment Report (CERI, NITE, 2007)). One report corresponds to Category 4 and four reports correspond to "Not classified" (one of them corresponds to "Not classified" (Category 5 in the UN GHS classification)). Therefore, this substance was classified as "Not classified" to which the greatest number of reports (three) corresponded.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Vapours)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). Besides, it is reported that when rats were exposed by inhalation to the saturated vapor of this substance for six hours (a converted 4-hour equivalent value: 6.0 ppm) (EU-RAR (2008), DFGOT Vol. 11 (1998)) or for eight hours (a converted 4-hour equivalent value: 6.9 ppm) (EU-RAR (2008)), there were no deaths in either case.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Dusts and mists)	Not classified	- -	-	-	On the basis of a reported LCLo value for rats (4 hours) of 5.6 mg/L (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), PATTY (6th, 2012), EU-RAR (2008), Hazard Assessment Report (CERI, NITE, 2007), DFGOT Vol. 11 (1998)), this substance was classified as "Not classified." Besides, as the test substance is a solid, the reference value for dusts was applied.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	It is reported that, in a skin irritation test with rabbits (OECD TG 404), severe irritation responses were observed as a result of a 4-hour semi-occlusive application of 500 mg of this substance, and these were resolved within 14 days (EU-RAR (2008)). It is reported that in separate skin irritation tests with rabbits (OECD TG 404), it was irritating (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)), severely irritating (EU-RAR (2008)), and corrosive (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). In addition, there is a report that, in a skin irritation study with rabbits (US DOT regulation 173.1300), severe irritation or corrosion was observed following a 4-hour semi-occlusive application of 500 mg of this substance (EU-RAR (2008)). There are also descriptions that necrosis, scabbing, and desquamation of the skin were observed following a 4-hour or 24-hour application of 500 mg of this substance but this was resolved by 17 days after administration (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2008), DFGOT Vol. 11 (1998)). In the EU-RAR (2008), it is regarded that this substance is severely irritating to the skin. From the above, this substance was classified in Category 2.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	It is reported that, in an eye irritation test with rabbits, severe corneal injury, iritis, and severe conjunctival irritation responses were observed following application of 10 mg or 80 mg of this substance. It is reported it was severely irritating, and reversibility was not seen in the case of 80 mg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2008)). From the above, this substance was classified in Category 1.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, as for occupational exposure, while there is a report that a bronchial provocation test with this substance elicited a dual asthmatic reaction (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008)), this report was judged to be insufficient for use in this classification as it involves only one case.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Skin sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, there are reports that this substance was negative in a maximization test with guinea pigs (OECD TG 406) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2008)). On the other hand, there are a few reports of positive reactions in patch tests in humans (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2008)). It is concluded in EU-RAR (2008) that this information on animal tests and humans are insufficient to draw a conclusion on this substance as a sensitizer (EU-RAR (2008)). Accordingly, this substance was classified as "Classification not possible."	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Germ cell mutagenicity	Classification not possible	- -	-	-	The substance was classified as "Classification not possible" because it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese Government. As for in vivo, this substance was negative in a micronucleus test in mouse bone marrow cells (Hazard Assessment Report (CERI, NITE, 2007), JECDB (Access on November 2015), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008)). As for in vitro, this substance was negative in bacterial reverse mutation tests and in a mouse lymphoma test with mammalian cultured cells, and positive and negative results were seen in chromosomal aberration tests with mammalian cultured cells (Hazard Assessment Report (CERI, NITE, 2007), JECDB (Access on November 2015), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008)).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Carcinogenicity	Classification not possible	- -	-	-	In a two-stage carcinogenicity study in which male rats were dosed with this substance in the diet at 15,000 ppm (equivalent to 1,070 mg/kg/day) for 51 weeks after being dosed with nitrosoguanidine (MNNG) as an initiator for one week, the treatment group that received MNNG pretreatment showed an increased incidence of papillomas or squamous cell carcinomas in the forestomach in comparison to the MNNG-pretreated control group, suggesting a promoter activity of this substance. However, it is described that the treatment group that only received this substance without MNNG pretreatment showed only hyperplasia in the forestomach and no increased incidence of tumors, and this substance has no initiating activity (SIDS (2012), Hazard Assessment Report (CERI, NITE, 2007)). There is no other information on the carcinogenicity of this substance. Therefore, classification was not possible due to lack of data.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	There is no information on the reproductive effects of this substance in humans. In experimental animals, in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with rats dosed by the oral route (OECD TG 422), no adverse effects on the fertility of the parents or on the survival rate or body weight changes in the pups through postnatal day 4 were seen at doses of up to 200 mg/kg/day (EU-RAR (2008), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), Hazard Assessment Report (CERI, NITE, 2007), PATTY (6th, 2012)). However, in a two-generation reproduction toxicity study with rats dosed by the oral route (by feeding), in the F0 parental animals, reduced body weight gain and reduced food consumption in both sexes and reduced ovary weights and atrophy of the vaginal epithelium in females were seen at 2,500 ppm (equivalent to 200 mg/kg/day) or higher. At 7,500 ppm (equivalent to 600 mg/kg/day), a decrease in the incidence of growing follicles, an increase in the incidence of primordial follicles, and changes in the estrous cycle (greater and lower incidences of females that were in proestrus and metoestrus, respectively) were observed, and a slight decrease in the number of implantation sites, and lower litter weight were also observed (EU-RAR (2008), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015)). In the F1 pups, reduced body weights were observed at 2,500 ppm or higher, and a slight decrease in litter size and a decrease in postnatal survival rate were seen at 7,500 ppm. Also in the F1 parental animals, reduced body weight gain (in males) and reduced food consumption (in females) were seen, and at 7,500 ppm, reduced body weight gain (in females), decreased ovarian and uterine weights, atrophy of the vaginal epithelium, and a change in the ratio of growing follicles to primordial follicles were observed similar to the F0 females. In the F2 pups, reduced body weights at 2,500 ppm or higher, and smaller litter size at 7,500 ppm were observed (EU-RAR (2008), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015)). As described above, no reproductive effects were detected in the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in rats. However, in the two-generation reproduction toxicity test with rats, at the doses where reduced body weight gain were seen in the parental animals of both the F0 and F1 generations, histological changes in the genetic organs and changes in the estrous cycle were observed in females, and smaller litter sizes and a decreased survival rate (in F1 pups only) in addition to reduced body weights. Therefore, this substance was classified in Category 2 for this hazard class. Besides, the EU classified this substance in Repr. 2 (ECHA CL Inventory (Access on November 2015)). The classification was changed based on the data from the information sources listed in List 1 such as the EU-RAR (2008) which was released after the previous classification.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
8	Specific target organ toxicity - Single exposure	Category 3 (Respiratory tract irritation)	Warning	H335	P304+P340 P403+P233 P261 P271 P312 P405 P501	This substance is severely irritating to the human respiratory tract, and cough and throat pain through inhalational exposure and nausea and vomiting through ingestion were seen (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015)). In experimental animals, sluggishness, unsteady gait, and prostration are reported in oral administration of rats (LD50 = 3620-5360 mg/kg, exceeding Category 2); perinasal, perioral, and periocular mucosal irritation and respiratory distress are reported in inhalation exposure in rats (5.6 mg/L, exceeding Category 2) (Hazard Assessment Report (CERI, NITE, 2007), EU-RAR (2008), SIDS (2012), PATTY (6th, 2012)). From the above, this substance is irritating to the respiratory tract and was classified in Category 3 (respiratory tract irritation).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	In humans, in addition to depigmentation of the skin, cases involving liver damage (impairment of liver functions, hepatomegaly, hepatocellular fatty degeneration and fibrosis etc.) or hypertrophy of the thyroid gland were reported in workers occupationally exposed to this substance in chemical plants in the UK and Australia in the 1970s (DFGOT Vol. 11 (1998)). However, workers exposed to this substance in chemical plants in Germany only showed depigmentation of the skin without any effects on the liver or thyroid gland. It is concluded in the EU risk assessment that, in humans, the effect of exposure to this substance is only depigmentation of the skin and there is no available data with regard to systemic toxicity effects (EU-RAR (2008)). Besides, it cannot be explained how the irritation/sensitization properties of this substance are involved in the depigmentation of the skin. Because electron microscopic investigations of biopsies of depigmented skin areas revealed a lack of melanocytes, defective melanocytes, etc., mechanisms such as a reduction in the production of melanin are being considered (EU-RAR (2008)). However, it is described that this effect of depigmentation of the skin is reversible by avoiding exposure to this substance and removing it from the skin (EU-RAR (2008)). In experimental animals, in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with rats dosed by the oral route (gavage), other than a noisy respiratory sound, which was considered to be caused by irritation, decreases in plasma albumin and total protein were observed at the high dose of 200 mg/kg/day (converted guidance value: 93 mg/kg/day), and there were no findings based on which a target organ can be specified (Hazard Assessment Report (CERI, NITE, 2007), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008)). In addition, in a two-generation reproduction toxicity study with rats dosed by the oral route (by feeding), at doses equivalent to 200-600 mg/kg/day which exceed the range of Category 2, reduced body weight gain, increased liver weights, atrophy of the vaginal epithelium, etc. were observed in the parental animals (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008)). In addition, in two-stage carcinogenicity studies in which male rats or male hamsters were dosed with this substance in the diet, hyperplasia in the forestomach were seen in the group dosed only with this substance in both rats and hamsters, but the converted dose exceeded 1,000 mg/kg/day (Hazard Assessment Report (CERI, NITE, 2007), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008)). As stated above, as for humans, it was assessed in DFGOT that according to the earlier study report, anomalies in the liver and thyroid gland were found in addition to depigmentation of the skin by occupational exposure (DFGOT Vol. 11 (1998)). However, it is concluded in the EU assessment that the skin is the only target organ in humans occupationally exposed to this substance (EU-RAR (2008)). Based on the findings in the experimental animals discussed above, there were no unequivocal changes by which the liver or thyroid gland can be identified to be a target organ of this substance. No target organ can be identified on the basis of other existing findings in experimental animals either. Therefore, since this substance is considered to be equivalent to "Not classified" for the oral route, but there is no information on toxicity by other exposure routes in experimental animals, this substance was classified as "Classification not possible" due to lack of data for this hazard class. Besides, the skin was not adopted as a target organ because the adverse effects on the skin of this substance were covered in the skin irritation/corrosion hazard class, and the vitiligo due to depigmentation was regarded to be a reversible change and judged to be of low severity. Also, the liver and thyroid gland, which were adopted as the target organs in the previous classification, were excluded for the reasons stated above.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

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)	Category 2	- -	H401	P273 P501	From 96-hour LC50/EC50 = 1.9 mg/L for crustacea (Crangon septemspinosa) (EU-RAR, 2008), it was classified in Category 2.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	Due to being not rapidly degradable (a degradation rate by 14-day BOD in an inherent test = 0%, a degradation rate by TOC = 1.2% (Official Bulletin of Ministry of International Trade and Industry, 1977)), and 72-hour NOEC (r) = 0.32 mg/L for algae (Pseudokirchneriella subcapitata) (EU-RAR, 2008, Environmental Risk Assessment for Chemical Substances vol. 13 (Ministry of the Environment, 2015)), it was classified in Category 2.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

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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