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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	98-56-6
Chemical Name	p-Chloro-alpha,alpha,alpha-trifluorotoluene
Substance ID	H30-A-002-MHLW, MOE
Classification year (FY)	FY2018
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)	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 applicable	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases (including chemically unstable gases)	Not applicable	- -	-	-	Liquid (GHS definition)
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Liquid (GHS definition)
5	Gases under pressure	Not applicable	- -	-	-	Liquid (GHS definition)
6	Flammable liquids	Category 3	Warning	H226	P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501	It was classified in Category 3 based on a flash point of 47 deg C (closed cup) (GESTIS (Accessed Oct. 2018)). Besides, it is classified in Class 3, PG III in UNRTDG (UN2234).
7	Flammable solids	Not applicable	- -	-	-	Liquid (GHS definition)
8	Self-reactive substances and mixtures	Not applicable	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9	Pyrophoric liquids	Classification not possible	- -	-	-	No data available.
10	Pyrophoric solids	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 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 applicable	- -	-	-	The substance is an organic compound containing chlorine and fluorine (but not oxygen) which are chemically bonded only to carbon or hydrogen.
14	Oxidizing solids	Not applicable	- -	-	-	Liquid (GHS definition)
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.

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] Based on both (1) and (2), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats (male): 5,546 mg/kg (REACH registration dossier (Accessed Nov. 2018)) (2) LD50 for rats (female): 7,270 mg/kg (REACH registration dossier (Accessed Nov. 2018))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified" (Category 5 in UN GHS classification or corresponds to "Not classified"). Besides, (2) in which an application duration is 5 hours, was not used for classification. [Evidence Data] (1) LD50 for rabbits: >2,000 mg/kg (REACH registration dossier (Accessed Nov. 2018)) [Reference Data, etc.] (2) LD50 for rabbits: >3,300 mg/kg (REACH registration dossier (Accessed Nov. 2018))
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	[Rationale for the Classification] Liquid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Category 4	Warning	H332	P304+P340 P261 P271 P312	[Rationale for the Classification] Based on (1), it was classified in Category 4. Besides, although "aerosol" is described in the test conditions, the LC50 value was lower than 90% of the saturated vapor concentration (10,066 ppm, 74.3 mg/L), so the reference values in units of ppm were applied as a vapour with little mist. [Evidence Data] (1) LC50 (4 hours) for rats: >32.03 mg/L (4,339 ppm) (REACH registration dossier (Accessed Nov. 2018))
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] Based on both (1) and (2), it was classified as "Not classified" (Category 3 in UN GHS classification). Besides, (3) was not adopted because details of the basis cannot be confirmed. [Evidence Data] (1) There is a report that as a result of 24-hour occlusive application of the undiluted liquid or a 10% solution (sesame oil) of this substance in a skin irritation test (n=6) with rabbits, an irritation score (erythema + edema) of 1.9 (undiluted) or 0.4 (10% solution), respectively was observed, and the animals did not recover within 72 hours (REACH registration dossier (Accessed Nov. 2018)). (2) There is a report that as a result of an 24-hour occlusive application of the undiluted liquid of this substance in a skin irritation test with rabbits, skin irritation was limited or not observed (GESTIS (Accessed Nov. 2018)). [Reference Data, etc.] (3) There is a report that this substance may cause skin irritation in humans (NTP TR594 (2018), HSDB (2011)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Besides, (2) and (3) were not adopted because the diluted solution was applied in (2), and the details of the basis cannot be confirmed for (3). [Evidence Data] (1) There is a report that as a result of application of the undiluted liquid of this substance in an eye irritation test with rabbits, slight irritation was observed after 24 hours but this resolved after 72 hours (GESTIS (Accessed Nov. 2018)). [Reference Data, etc.] (2) There is a report that as a result of 24-hour application of 10% solution (sesame oil) of this substance in an eye irritation test (FDA guideline (FEDERAL REGISTER vol. 38 n.187, s.27019/1973), n=6) with rabbits, irritation score (the cornea, iris, and conjunctiva) after 24 hours was 0 (completely recovered) (REACH registration dossier (Accessed Nov. 2018)). (3) There is a report that this substance may cause eye irritation in humans (NTP TR594 (2018), HSDB (2011)) (NTP TR594 (2018), HSDB (2011)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] Based on (1), it was classified in Category 1. [Evidence Data] (1) There is a report that as a result of application of a 75%, 50% or 25% solution (dimethylformamide) of this substance (purity 99.3%), respectively in a LLNA test (OECD TG429, GLP, n=4/group) with mice, a stimulation index (SI) of 7.3, 6.9, 8.1 was obtained, respectively, and then sensitization was observed (REACH registration dossier (Accessed Nov. 2018)).
5	Germ cell mutagenicity	Classification not possible	- -	-	-	[Rationale for the Classification] As for in vivo, positive or ambiguous (1) and negative (2) results were obtained. In (3), there are many reports of being negative in vitro. In-vivo mutagenicity of this substance cannot be clearly judged to be positive. Therefore, it was classified as "Classification not possible" in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) This substance was positive (male) or ambiguous (female) in an in-vivo micronucleus test with mice exposed by inhalation for 3 months (NTP TR594 (2018)). (2) This substance was negative in an in-vivo chromosomal aberration test with rats dosed by gavage (NTP TR 594 (2018), HSDB (2011)). (3) As for in vitro, a positive result was obtained in a sister chromatid exchange test with cultured mammalian cells, but in a bacterial reverse mutation test, a mouse lymphoma test, and a chromosomal aberration test with cultured mammalian cells, this substance was negative (NTP TR 594 (2018), HSDB (2011)).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Information on carcinogenicity in humans is limited to (4). However, it was classified in Category 1B since there are results indicating carcinogenicity in two species based on both (1) and (2). [Evidence Data] (1) In a carcinogenicity study with rats exposed by inhalation (100-1,000 ppm) for two years, increased incidences of C-cell adenoma of the thyroid gland in males and females, and in females, increased incidences of pheochromocytoma of the adrenal medulla, and of adenocarcinomas and stromal polyp of the uterus were observed. The increased combined incidence of bronchioloalveolar adenoma or carcinoma in male rats was also considered to be treatment-related tumorigenesis. Based on these, it was concluded that there is some evidence for carcinogenicity in this substance in both male and female rats (NTP TR594 (2018)). (2) In a carcinogenicity study with mice exposed by inhalation (100-400 ppm) for two years, increased incidences of hepatocellular carcinoma and hepatoblastoma in males and females, and hepatocellular adenoma in females were observed. The increased incidence of adenoma in the Harderian gland of female mice was also considered to be treatment-related tumorigenesis. Based on these, it was concluded that there is clear evidence for the carcinogenicity of this substance in both male and female mice (NTP TR594 (2018)). (3) There are no classification results by domestic and international organizations. [Reference Data, etc.] (4) There is a report that incidences of respiratory organs cancer and stomach cancer were higher in an epidemiological study of a small cohort of workers at plants in the United States. However, workers had received combined exposure to many chemicals other than this substance (NTP TR594 (2018)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] As for data in (1), in a reproductive toxicity study with rats, there were no adverse effects on the fertility in the F0 parents, but general toxic effects such as blood effects and decreased body weight gain were observed in the F1 pups of treated groups. However, since these general toxic effects in the F1 animals were not effects via maternal body by administration to the parental animals but could be due to direct exposure after weaning, these effects were considered to be not applicable to evaluate reproductive toxicity effects. There are no other data available for classification, so it was classified as "Classification not possible." [Reference Data, etc.] (1) F0 paternal and maternal animals of rats were dosed by gavage at up to 45 mg/kg/day for total 76-83 days from 4 weeks before mating to weaning of F1 through the mating and gestation period, and F1 after weaning was orally dosed at the same dose as their parents for 90 days. As the result, in F1 pups, general toxic effects (blood effects (decreases in erythrocyte count and hemoglobin, increased MCV), non-neoplastic lesions of the lung, and decreased body weight gain in the high dose group of females) were observed, but reproductive indexes of F0 parental animals (litter size, survival rate of pups) were higher than those of the control group, and no effect on fertility index was observed (NTP TR594 (2018), HSDB (2011)).
8	Specific target organ toxicity - Single exposure	Category 3 (Respiratory tract irritation)	Warning	H335	P304+P340 P403+P233 P261 P271 P312 P405 P501	[Rationale for the Classification] Based on both (1) and (2), it was classified in Category 3 (respiratory tract irritation). Besides, as for (3), 9,000 ppm (66.5 mg/L), the highest concentration tested is a concentration near 90% (9,059 ppm) of the saturated vapor pressure (10,066 ppm), and the test air is presumed to be a vapor containing mist, but it is a concentration exceeding Category 2 for both mist and vapour criterion. Since the presence or absence of symptoms at lower concentrations are unknown, it was not used for classification. [Evidence Data] (1) Human exposure may cause irritation at the site of contact (eye, skin, respiratory organs) (NTP TR594 (2018)). (2) In humans, there are reports on symptoms in the respiratory organs such as cough, shortness of breath, chest pain after inhalation exposure (NTP TR594 (2018)). [Reference Data, etc.] (3) There is a report that in a single inhalation exposure test with rats, by 4-hour exposure of up to 9,000 ppm, as symptoms, muscle spasm, labored breath, salivation, ataxia of extremities, increased irritability to touch, upon necropsy, dark lung with white spots and bleeding-like changes in the thymus were observed (NTP TR594 (2018)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (respiratory organs, liver, adrenal gland)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on both (1) and (3), in the inhalation exposure with rats, the lung (respiratory organs), liver and kidney were considered as candidates for targets, within the range of Category 2. Similarly, based on both (2) and (4), the lung and liver were considered as target organs, within the range of Category 2 in the inhalation exposure with mice. On the other hand, in the oral route, based on both (5) and (6), in rats, the liver, kidney, and adrenal gland were considered as target organs, and in mice, the liver was considered as target organ, within the range of Category 2. Of these, the adrenal gland was included as the target organ since effects were also observed at high doses exceeding Category 2 even in the inhalation exposure test with rats in (1) and (3), and as for kidney, based on the data in (5), it was judged that the probability of kidney damage based on male rat-specific alpha 2u-globulin nephropathy is high, so this was not adopted as target organ. Therefore, it was classified in Category 2 (respiratory organs, liver, adrenal gland). [Evidence Data] (1) In a 14-week inhalation exposure test with rats, increased ALP activity (male), effects on the kidney (male: increased weights, and hyaline droplet deposition, chronic nephropathy) at or above 125 ppm (converted guidance value: 0.72 mg/L) within the range of Category 2, effects on the liver (increased weights, centrilobular hepatocytes hypertrophy (male), increased ALP activity (female)), and degeneration of the Harderian gland at or above 250 ppm (converted guidance value: 1.44 mg/L) exceeding the range of Category 2, and vacuolation of adrenal cortex cytoplasm, etc. in addition to clarified effects on liver at 500-2,000 ppm were observed (NTP TR594 (2018)). (2) In a 14-week inhalation exposure test with mice, effects were observed at or above 250 ppm (converted guidance value: 1.44 mg/L) exceeding the range of Category 2, and changes in the red pulp of the spleen (erythrocytic hematopoietic cell proliferation and megakaryocytes proliferation) in addition to effects on the liver and adrenal glands similar to rats were observed within the dose range of 250-2,000 ppm (NTP TR594 (2018)). (3) In a 2-year inhalation exposure test with rats, effects on the lung (chronic inflammation, fibrosis, hemorrhage), liver (centrilobular hepatocytes hypertrophy), kidney (male: increased severity of nephropathy) at or above 100 ppm (converted guidance value: 0.74 mg/L) within the range of Category 2, and clarified effects on the liver, hyperplasia of the endometrium, hyperplasia of the adrenal medulla, etc. at 300-1,000 ppm exceeding the range of Category 2 were observed (NTP TR594 (2018)). (4) In a 2-year inhalation exposure test with mice, effects on the lung (bronchioloalveolar hyperplasia, peribronchiolar fibrosis), liver (centrilobular hepatocytes hypertrophy, increased eosinophilic foci, increased multinucleated hepatocytes, etc.) were observed at 100 and 200 ppm (converted guidance value: 0.74-1.48 mg/L) within the range of Category 2 (NTP TR594 (2018)). (5) In the oral route, in 14-day tests with rats or mice dosed by gavage, in rats, nephropathy due to hyaline droplet deposition in the kidneys of males was observed at 50 mg/kg/day (converted guidance value: 7.8 mg/kg/day) within the range of Category 1, and ELISA assay showed a dose-related increase in alpha 2u-globulin in the kidney. Hepatocellular hypertrophy and cytoplasmic vacuolization of the adrenal glands in rats, and hepatocellular hypertrophy, cholestasis, mild liver injury in mice were observed at or above 400 mg/kg/day (converted guidance value: 62.2 mg/kg/day) within the range of Category 2 (NTP (1992)). (6) In a 3-month test with rats dosed by gavage, increased liver weights, increased ALP activity, renal tubular degeneration (male) were observed at 10 and 40 mg/kg/day within the range of Category 2, and effects on the liver, kidney, blood, etc. were observed at high doses exceeding Category 2 (HSDB (2011)).
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 (Acute)	Classification not possible	- -	-	-	Reliable acute toxicity data were not obtained.
11	Hazardous to the aquatic environment (Long-term)	Classification not possible	- -	-	-	No data available.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.

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.

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