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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	120-82-1
Chemical Name	1,2,4-Trichlorobenzene
Substance ID	H30-B-030-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	Revised
Classification result in other fiscal year	FY2008 FY2006
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	Not classified	- -	-	-	A flash point is 110 deg C (closed cup) (GESTIS (Accessed Sept. 2018)).
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	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 571 deg C (GESTIS (Accessed Sept. 2018)).
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 (but not fluorine or oxygen) which is 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)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] The data in (1)-(3) which are according to OECD TG 401 are adopted preferentially, and all of them correspond to Category 4. Therefore, it was classified in Category 4. [Evidence Data] (1) LD50 for rats: 1,107 mg/kg (male) (OECD TG 401) (EU-RAR (2003)) (2) LD50 for rats: 1,019 mg/kg (female) (OECD TG 401) (EU-RAR (2003)) (3) LD50 for rats: 930 mg/kg (OECD TG 401) (EU-RAR (2003)) [Reference Data, etc.] (4) LD50 for rats: 756 mg/kg (female) (EU-RAR (2003), ACGIH (7th, 2001), Patty (2012))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] As for rats, the data in (1) which are according to OECD TG 402 are adopted preferentially, and it can be judged as "Not classified." In addition, as for rabbits, it can be determined as "Not classified" based on the data in (2) and (3). Therefore, it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: 11,356 mg/kg (OECD TG402) (EU-RAR (2003), REACH registration dossier (Accessed Oct. 2018)) (2) LD50 for rabbits: about 5,000 mg/kg (EU-RAR (2003)) (3) LD50 for rabbit: > 5,000 mg/kg (EU-RAR (2003), REACH registration dossier (Accessed Oct. 2018)) [Reference Data, etc.] (4) LD50 for rats: 6,139 mg/kg (EU-RAR (2003), ACGIH (7th, 2001))
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	[Rationale for the Classification] Liquid (GHS definition)
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)	Not classified	- -	-	-	[Rationale for the Classification] Based on data in (1) and (3), it is considered to correspond to Category 4 - "Not classified." In addition, from data in (2), it is possible to determine as "Not classified." Therefore, it was classified as "Not classified." Besides, since the exposure concentration is higher than the saturated vapor concentration (2.5 mg/L), a reference value in units of mg/L was applied assuming that the mist was mixed in tests in (1)-(3). [Evidence Data] (1) LD0 for rats: 3.1 mg/L (418 ppm) (EU-RAR (2003)) (2) LD0 for rats: 13.6 mg/L (1,800 ppm) (7 hours) (converted 4-hour equivalent value: 17.7 mg/L) (EU-RAR (2003)) (3) LD0 for rats: 2.5 mg/L (330 ppm) (7.5 hours) (converted 4-hour equivalent value: 3.4 mg/L (452 ppm)) (EU-RAR (2003))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Besides, there are also data in (2) and (3), but the test details are unknown. The data in (4) cite the ICSC, and information of the information sources in List 1 was prioritized. [Evidence Data] (1) There is a report that in a skin irritation test (OECD TG404, n=6) with rabbits, as for this substance itself, slight irritation with an erythema score 1 and oedema score 1 was observed during the 14-day observation period (EU-RAR (2003), REACH registration dossier (Accessed Sept. 2018)). [Reference Data, etc.] (2) There is a report that in a skin irritation test with guinea pigs, this substance was moderately irritating to young animals and severely irritating to older animals (EU-RAR (2003), ATSDR (2014)). (3) There is a report that in mice, erythema was observed in 4/8 animals (EU-RAR (2003)). (4) There is a report that this substance causes skin dryness, redness and skin roughness when contacted on the skin (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010)). (5) It is reported that there is clear evidence that inflammation and defatting of the skin occur by repeated exposure (EU-RAR (2003), Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010)). (6) As for classifications by other organizations, it was classified as "Skin Irrit. 2" by the EU.
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." As for data in (2), since it is also described that the interpretation of the Draize score is different between the United States and Europe, and the test details could not be confirmed, it was not used for classification judgment. The data in (3) cite the ICSC, and the information of the information source in List 1 was prioritized. [Evidence Data] (1) There is a report that in an eye irritation test (OECD TG 405) with rabbits, no effects on the cornea and the iris were observed, redness score of 1 and edema score of 0-2 were obtained in the conjunctiva (EU RAR (2003), REACH registration dossier (Accessed Sept. 2018)). [Reference Data, etc.] (2) There is a report that in an eye irritation test with rabbits, severe conjunctivitis occurred and this did not resolve after 48 hours (EU-RAR (2003)). (3) There is a report that this substance causes redness and pain when it enters the eyes (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] There are also data in (1) and (2), but classification was not possible due to lack of data. Since human findings were not obtained, the category was changed from the previous classification. [Reference Data, etc.] (1) There is a report that in a Maximization test (OECD TG406, n=20) with guinea pigs, sensitization was observed in 2/20 animals (EU-RAR (2003), REACH registration dossier (Accessed Sept. 2018)). (2) There is a report that no positive reaction was observed in a skin sensitization test with guinea pigs (EU-RAR (2003)).
5	Germ cell mutagenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Classification not possible" in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) As for in vivo, it showed a negative result in an in vivo micronucleus test (OECD TG 474, GLP) with mice dosed orally (EU-RAR (2003)). (2) As for in vitro, it was negative in bacterial reverse mutation tests (EU-RAR (2003), ATSDR (2014)) and negative in a mammalian cell chromosome aberration test (EU-RAR (2003), Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010)). [Reference Data] (3) Slightly positive reactions were observed in 2 tests of in vivo micronucleus tests with mice dosed intraperitoneally (EU-RAR (2003), ATSDR (2014)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] As for carcinogenicity, there are no available reports on humans. Based on the data in (1) and (2), an increased incidence of malignant tumors was observed in male and female mice, but in rats, there was only a tendency of increased incidence of Zymbal's gland tumors in males, and evidence of carcinogenicity was limited. The classification result of EPA in (4) is one obtained by using only the dermal test result in (3) as the evaluation target, and it is no longer applicable due to older classification results. From the above results, it was judged as appropriate that it was Category 2 for this hazard class. [Evidence Data] (1) In a carcinogenicity study with rats (dietary administration for 2 years: 100-1,200 ppm (male: 5.5-67 mg/kg/day, female: 6.7-79 mg/kg/day), 50 animals/sex/group), no increase in tumor development was observed in females, but a non-significant, tendency to increase Zymbal's gland tumors was shown in males (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010), EU-RAR (2003), ATSDR (2014)). (2) In a carcinogenicity study with mice (dietary administration for 2 years: 150-3,200 ppm (male: 21-522 mg/kg/day, female: 26-575 mg/kg/day), 50 animals/sex/group), a significant increase in the incidence of the hepatocellular carcinoma was observed at or above the middle dose (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010), EU-RAR (2003), ATSDR (2014)). (3) In a carcinogenicity study in which 0.03 mL (9 and 18 mg/animal) of 30% and 60% solutions of this substance were applied to mouse skin for 2 years, at the high concentration group, papillomas were observed in two males and squamous cell carcinomas in one female (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010), EU-RAR (2003)). (4) As for classification results by domestic and international organizations, it was classified as D (Not classifiable as to human carcinogenicity) by EPA, but it was classified in 1989, and only the dermal application test result with mice in (3) was evaluated (IRIS (1989), ATSDR (2014)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Reproductive and developmental toxicity was not detected in the two-generation study with rats in (1). However, the only effect observed at the highest dose was an increase in the weight of the adrenal gland at weaning of F0 and F1 pups, and neither general toxic effects nor reproductive effects were observed in F0 and F1 parental animals after maturation. Therefore, it is considered that the highest dose did not reach an assured intoxication dose. In addition, among the 2 developmental toxicity test results in (2) and (3), the data in (3) are considered inappropriate for classification because the mortality rate of maternal animals is beyond 10%. From the above, it is inadequate information to evaluate the reproductive and developmental effects of this substance. Therefore, classification was not possible due to lack of data. [Reference Data, etc.] (1) Maternal rats were administered by drinking water (25-400 ppm), and F0 pups were administered indirectly exposed via dams milk until weaning, and after weaning, they were directly administered the same dose as maternal animals by drinking water, mated at about 90 days of age, and administered until weaning of F1 pups. In a two-generation reproductive toxicity study in which F1 pups were also administered by drinking water at the same dose after weaning and mated similarly to F0, increased adrenal gland weight was observed in males and females at high dose of F0 and F1 pups (400 ppm: 53.6 mg/kg/day (F0 male), 33.0 mg/kg/day (F0 female)), but fertility in F0 and F1 parental animals after rearing and fetotoxicity or developmental effects on F1 and F2 pups were not observed (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010), ATSDR (2014)). (2) In a developmental toxicity test with rats administered by gavage on gestational day 6-15, maternal animals showed general toxicity such as decreased hemoglobin and hematocrit, and effects on the liver (increased periportal cytoplasmic eosinophilia, anisokaryosis of hepatocytes) at or above 150 mg/kg/day and decreased thyroid follicle size and vacuolation at 300 mg/kg/day, but no significant change was observed in fetuses (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010), ATSDR (2014)). (3) In a developmental toxicity test dosed by gavage on gestational day 9 -13 of pregnant rats and performed cesarean section on gestational day 14, serious maternal toxicity (death (2/9 animals), decreased body weight gain, hepatocytes hypertrophy) was manifested in the treated group of 360 mg/kg/day, decreased number of implantations, increased fetal death, decreases in head length and crown-rump length and a decrease in the number of somites were observed, but there was no increase in the incidence of resorptions or malformations (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010), ATSDR (2014)).
8	Specific target organ toxicity - Single exposure	Category 3 (narcotic effects, respiratory tract irritation)	Warning	H336 H335	P304+P340 P403+P233 P261 P271 P312 P405 P501	[Rationale for the Classification] Respiratory tract irritation from (1) and lethargy from (2) which suggests central depression and is considered to support narcotic effects were found. Therefore, it was classified in Category 3 (narcotic effects, respiratory tract irritation). [Evidence Data] (1) There is a description that eye and throat irritation is considered to occur at 3-5 ppm in humans (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010), ATSDR (2014)). (2) In a test in which rats were exposed by inhalation to this substance (vapor) for 6 hours, lethargy and lacrimation were observed at or above 70 ppm (converted guidance value: 0.64 mg/L) within the range of Category 1 (ATSDR (2014)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (liver)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on the data in (1)-(5), the liver, kidney, thyroid, and hemal system are considered as candidate target organs, but from the view of ATSDR on the target organs of this substance in (6), effects on the kidney are likely due to a mechanism specific to male rats, and effects on thyroid in the 13-week administration with rats in (1) were not observed in the 2-year chronic study in (3) and (4). Therefore, both kidney and thyroid are excluded from the target organs. In addition, as for effects on the blood, since no effects are observed by hematology/blood biochemistry tests in most of the many studies through oral, dermal and inhalation routes, ATSDR is skeptical about effects on the blood, and it is not adopted as the target organ since it is not seen as a clear finding within the dose range of Category 2 in the oral administration studies in (1)-(4). From the above, it was classified in Category 2 (liver). Besides, the kidney, thyroid and hemal systems as target organs were excluded from the previous classification, and only the liver was adopted. Besides, (7) was not adopted since the liver effect became weaker as the exposure period increased. [Evidence Data] (1) In a 13-week test with rats administered by feeding, at 1,000 ppm (male/female: 82/101 mg/kg/day) within the range of Category 2, effects on the liver (weight increase, fatty infiltration, hepatocyte vacuolation and degeneration) and effects on the thyroid (reduction in follicular size, increased follicular epithelial height, reduced colloid density) were observed (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010), ATSDR (2014), EU-RAR (2003)). (2) In a 3-month test with rats administered by feeding, in the groups at or above 600 ppm (male: 32-96 mg/kg/day, female: 40-108 mg/kg/day) within the range of Category 2, effects on the kidney (increased relative weight (male and female), tubule dilation, granular casts, hyaline droplet, renal papilla mineralization, interstitial nephritis and tubule regeneration (male)), effects on the liver (increased absolute and relative weight (female)), centrilobular hepatocyte hypertrophy (male), at 1,800 ppm (male: 96-242 mg/kg/day, female: 108-276 mg/kg/day), which is upper limit of Category 2-exceeding the range of Category 2, effects on the blood (a decrease in erythrocyte count (male), decreases in hemoglobin and hematocrit (male and female)) were observed (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010), ATSDR (2014), EU-RAR (2003)). (3) In a 104-week test with rats administered by feeding, at 350-1,200 ppm within the range of Category 2, in addition to effects on the liver, effects on the kidney (increased weight (male and female), deterioration of chronic progressive nephropathy (male), renal papilla mineralization (male and female), hyperplasia of the tubular transitional epithelial cells (male)) were observed in males and females (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010), ATSDR (2014), EU-RAR (2003)). (4) In a 104-week test with mice administered by feeding, at 700 ppm (100.5 mg/kg/day (male)) and 3,200 ppm (522 (male)/574 (female) mg/kg/day) exceeding the range of Category 2, centrilobular hepatocyte hypertrophy was observed, but no effects on the kidney were seen in either sex (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010), ATSDR (2014), EU-RAR (2003)). (5) In a 4-week test in which a commercial product of this substance (containing 70% of this substance and 30% of 1,2,3-TCB) was dermally administered to rabbits, at 150 and 450 mg/kg/day (converted guidance value: 33.0 and 98.9 mg/kg/day) within the range of Category 2, effects on the blood (decreases in erythrocyte count, hemoglobin and hematocrit value) were seen in females (EU-RAR (2003)). (6) ATSDR indicated that histological findings of the kidney may be associated with alpha 2u-globulin nephropathy specific to male rats, and that findings of the thyroid observed in a 13-week test with rats were not observed at similar doses in a long-term study with rats nor a study with mice. In addition, it is described that in the dermal test with rabbits in (5), changes in hematological parameters were observed but within the normal range, and no hematological effects were observed from the test reports in the dermal and inhalation routes (ATSDR (2014)). [Reference Data, etc.] (7) In the inhalation route, in an inhalation exposure test with male rats for up to 26 weeks, at or above 25 ppm (converted guidance value: 0.16 mg/L) within the range of Category 1, hepatocellular hypertrophy in the liver and hyaline droplet degeneration in the kidney were observed at the end of 13-week exposure which is half the time of the test duration. However, these changes were not observed clearly at the end of the 26-week exposure and are considered to be relatively short-term changes (Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010), ATSDR (2014), EU-RAR (2003)).
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)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 48-hour EC50/LC50 = 0.308 mg/L for crustacea (Ceriodaphnia dubia) (WHO/IPCS CICAD: 2004).
11	Hazardous to the aquatic environment (Long-term)	Category 1	Warning	H410	P273 P391 P501	It was classified in Category 1 because it is not rapidly degradable (not readily degradable, a degradation rate by BOD: 0% (J-CHECK, 1977)), and due to 21-day NOEC (reproduction inhibition) = 0.1 mg/L for crustacea (Daphnia magna) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2018), Environmental Risk Assessment for Chemical Substances Vol. 8 (Ministry of the Environment, 2010)).
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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