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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	71-55-6
Chemical Name	1,1,1-Trichloroethane
Substance ID	R03-B-029-METI, MOE
Classification year (FY)	FY2021
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/Ministry of the Environment (MOE)
New/Revised	Revised
Classification result in other fiscal year	FY2018 FY2014 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 (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)	- -	-	-	Liquid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
6	Flammable liquids	Not classified	- -	-	-	It is not combustible (GESTIS (Accessed Aug. 2021)). Besides, its vapours may form an explosive atmosphere in closed rooms if ignited by sparks or a high energy flame.(GESTIS (Accessed Aug. 2021)).
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
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	- -	-	-	It is not combustible (GESTIS (Accessed Aug. 2021)).
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
11	Self-heating substances and mixtures	Not classified	- -	-	-	It is not combustible (GESTIS (Accessed Aug. 2021)).
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)	- -	-	-	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 classified (Not applicable)	- -	-	-	Liquid (GHS definition)
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
16	Corrosive to metals	Category 1	Warning	H290	P234 P390 P406	There is information that it is extremely corrosive to aluminum, and dry 1,1,1-trichloroethane moderately corrodes iron and zinc. (HSDB in PubChem (Accessed Aug. 2021)).
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)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (5), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (OECD TG 401) (SIAR (2009)) (2) LD50 for rats (males): 12,300 mg/kg (SIAR (2009), ATSDR (2006)) (3) LD50 for rats (females): 10,300 mg/kg (SIAR (2009), ATSDR (2006)) (4) LD50 for rats (males): 17,148 mg/kg (SIAR (2009), ATSDR (2006)) (5) LD50 for rats (females): 12,996 mg/kg (SIAR (2009), ATSDR (2006))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (OECD TG 402) (SIAR (2009))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified."
1	Acute toxicity (Inhalation: Vapours)	Category 4	Warning	H332	P304+P340 P261 P271 P312	[Rationale for the Classification] Based on (1) to (7), it was classified in Category 4. Also, since the exposure concentration was lower than 90% (146,805 ppm) of the saturated vapor concentration (16,528 ppm), it was judged to be a vapor without a mist and classified based on the reference value in units of ppmV. Based on the new findings, classification result was changed. [Evidence Data] (1) LC50 (3 hours) for rats: 18,000 ppm (converted 4-hour equivalent value: 15,588 ppm) (SIAR (2009), US AEGL (2000), EHC 136 (1990)) (2) LC50 (7 hours) for rats: 14,250 ppm (converted 4-hour equivalent value: 18,851 ppm) (SIAR (2009), ATSDR (2006), US AEGL (2000), EHC 136 (1990)) (3) LC50 (6 hours) for rats (males): 10,305 ppm (converted 4-hour equivalent value: 12,621 ppm) (SIAR (2009), ATSDR (2006), US AEGL (2000), EHC 136 (1990)) (4) LC50 (4 hours) for rats (males): 18,425 to 21,033 ppm (US AEGL (2000)) (5) LC50 (4 hours) for rats (females): 18,000 ppm (US AEGL (2000)) (6) LC50 (4 hours) for rats: 18,400 ppm (US AEGL (2000), EHC 136 (1990)) (7) LC50 (4 hours) for rats: 13,338 ppm (males: 13,268 ppm, females: 13,426 ppm) (US AEGL (2000))
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	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 2. [Evidence Data] (1) As for local effects resulting from dermal exposure to this substance, as exposure duration increased, the severity of effects increased from mild irritation to chemical burns, but irritation effects were reversible (SIAR (2006)). (2) In an acute dermal irritation/corrosion test with rabbits (OECD TG 404, semi-occlusive, 4-hour application), this substance was reported to be a skin irritant (SIAR (2009), EHC 136 (1990)). (3) It was reported that, in an acute dermal irritation/corrosion test with rabbits (n=3) (equivalent to OECD TG 404, semiocclusive, 4-hour application, observation for 16 days), erythema was not reversible until 16 days later (average score for erythema on Day 16: 0.3) and the primary dermal irritation index (PII) was 5.2 (erythema score: 4/4/3, edema score: 2/1.3/1.3) (REACH registration dossier (Accessed August 2021)).
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 2B in accordance with the GHS Classification Guidance for the Japanese Government. Also, based on the new findings, classification result was changed. [Evidence Data] (1) It was reported that, in a study with volunteers, mild eye irritation was observed after exposure to concentrations at or above 450 ppm for 4 hours (US AEGL (2000), SCOEL (1995)). (2) It was reported that volunteers exposed to vapor of this substance at concentrations exceeding 1,000 ppm for 20 to 73 minutes complained of mild eye irritation, while eye irritation was not indicated in other volunteers exposed for 186 minutes at a vapor concentration of approximately 500 ppm (ATSDR (2006) p. 87/371). (3) It was reported that, in an eye irritation test with rabbits, mild irritation was observed (ATSDR (2006), EHC 136 (1990)). (4) It was reported that, in an eye irritation test with rabbits (100 mg), slight to moderate pain and slight conjunctival irritation were caused but there was no corneal damage, and any irritation which occurred disappeared within a few days (SIAR (2009), REACH registration dossier (Accessed Sep. 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), the sensitization rate was less than 30%, and it was classified as "Not classified." [Evidence Data] (1) It was reported that, in a Maximization test (OECD TG 406, GLP, intradermal induction: 10% solution) with guinea pigs (n=20), the positive rate was 10% (2/20 animals) and 15% (3/20 animals) at 24 and 48 hours after challenge, respectively (REACH registration dossier (Accessed Sep. 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, equivocal (males) and negative (females) results were obtained in a micronucleus test using the peripheral blood of mice (dosed by feeding for 90 days), and negative results were obtained in three micronucleus tests using the bone marrow cells of mice (one acute inhalation exposure test, two 2-day intraperitoneal injection test) and a dominant lethal assay using mice (dosed by drinking water) (SIAR (2009), ATSDR (2006)). (2) As for in vitro, negative (in open systems) and positive (in closed systems) results in a bacterial reverse mutation test, negative results in a mouse lymphoma assay, and positive (S9-) or equivocal results in a chromosomal aberration test using CHO cells or CHL cells were obtained (SIAR (2009), Mutagenicity Test Data of Existing Chemical Substances based on the toxicity investigation system of the Industrial Safety and Health Law (Accessed August 2021)).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1B. In (1) and (2), clear evidence of carcinogenicity including malignant tumor was observed in two animal species. [Evidence Data] (1) In a carcinogenicity study with rats by inhalation exposure for 2 years, increased incidences of peritoneal mesotheliomas were observed in males (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 1998)). The lot of this substance used in this study contained 3.34 to 3.50% 1,4-dioxane (CAS RN 123-91-1), as a stabilizer, which was a known carcinogen (GHS classification result in FY2018: Category 1B) (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 1998)). (2) In a carcinogenicity study with mice by inhalation exposure for 2 years, increased incidences of Harderian gland adenomas, malignant lymphomas derived from the spleen and bronchiolo-alveolar epithelium carcinomas in males and hepatocellular adenomas and bronchiolo-alveolar epithelium adenomas in females were observed (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 1998)). The information about the lot of this substance used in this study was the same as (1). (3) As for the classification results by domestic and international organizations, the IARC classified it in Group 3 (IARC 71 (1999)), the EPA classified it in Group D (IRIS (2007)) and the ACGIH classified it in A4 (ACGIH (7th, 2001)). Also, these evaluations and the OECD SIDS assessment do not include the results of (1) and (2). (4) This substance is a target substance in the public announcement on guidelines in order to prevent the impairment of worker's health caused by the chemical substances decided by the Minister of Health, Labour and Welfare based on paragraph (3) of Article 28 of the Industrial Safety and Health Act (guidelines in order to prevent the impairment of worker's health, announcement No. 23 on October 10, 2012). [Reference Data, etc.] (5) In a carcinogenicity study with rats and mice by inhalation exposure for 2 years (150 to 1,500 ppm), a trend toward increased incidences of benign tumours of the Harderian gland was observed in female mice, but it was within the range of laboratory's historical data. No significant increase in the incidence of tumors was observed in male and female rats and male mice (IARC 71 (1999), IRIS (2007), Patty (6th, 2012)). Also, the purity of the test substance used in the study was 94%, and 5% of the stabilizer contained 1,2-butylene oxide (CAS RN 106-88-7) (composition ratio unknown) (IARC 71 (1999)), which was a suspected carcinogen (GHS classification result in FY2021: Category 2). (6) Most of the studies that evaluated the associations between cancers and occupational exposure to this substance did not find associations. However, it was reported that a study of Finnish workers found statistically significantly increased standardized incidence ratios for cancer of the nervous system and multiple myeloma in male and female workers exposed to this substance and an increased risk of multiple myeloma was also seen in workers exposed to this substance at an aircraft maintenance facility in Utah. However, because these studies were based on a small number of cases and because workers were exposed to multiple solvents, the results were difficult to interpret (SIAR (2009)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1B. Also, in a test with mice in (1), a decrease in litter size was observed at a dose at which no general toxicity was observed in parental animals, and in addition, in (2) and (3), an increase in mortality rate at birth, developmental delays after birth, behavior disorder, etc. were observed at a dose at which general toxicity was observed. Based on the new findings, classification result was changed. [Evidence Data] (1) It was reported that, in a developmental toxicity study with mice by inhalation exposure (days 12 to 17 of gestation, 17 hours/day), at 2,000 ppm, a decrease in litter size, reduced body weight gain after birth, apparent developmental delays (pinnae detachment, incisor eruption, eye opening), and impaired performance in behavioral tests were observed in pups (ATSDR (2006)). (2) It was reported that, in a developmental toxicity study with mice by inhalation exposure (days 12 to 17 of gestation, 3 times/day, for 60 minutes), at 8,000 ppm, clinical signs (anesthetized state, mild tremors, gait abnormalities) were observed in parental animals, and reduced body weight gain after birth, apparent developmental delays (pinnae detachment, incisor eruption, eye opening), and impaired performance in behavioral tests (righting reflex, forelimb grip strength, negative geotaxis, rooting reflex) were observed in pups (ATSDR (2006)). (3) It was reported that, in a developmental toxicity study with rats by inhalation exposure (days 13 to 19 of gestation, 3 times/day, for 60 minutes), at 7,000 ppm, reduced body weight gain, clinical signs (salivation, lacrimation, abnormal gait), complete embryo resorption (2/9 dams), and an increase in gestation length were observed in parental animals, and increased mortality at birth, decreased litter weight, and decreases in coordination, muscle strength, and spontaneous motor activity were observed in pups (ATSDR (2006), SIAR (2009)). [Reference Data, etc.] (4) It was reported that, in a developmental toxicity study with rats by inhalation exposure (days 6 to 15 of gestation, 6 hours/day), at 6,000 ppm, reduced body weight gain, decreased food consumption, hypoactivity, and decreased gravid uterine weight were observed in parental animals, and only minor developmental effects (lower fetal body weight (females), delayed ossification (cervical vertebra)) were observed in pups (SIAR (2009)). (5) It was reported that, in a developmental toxicity study with rabbits by inhalation exposure, at 6,000 ppm, reduced body weight gain was observed in parental animals and only increased incidences of extra ribs were observed in fetuses (ATSDR (2006)). (6) It was reported that, in a two-generation reproduction toxicity study with mice dosed by drinking water, no general toxicity effects or effects on fertility in parental animals or pups were observed at doses up to 1,000 mg/kg/day (SIAR (2009)). (7) It was reported that, in a neurologically developmental toxicity study with rats dosed by gavage (day 6 of gestation to day 10 of lactation), no effects on neurodevelopmental indices in liveborn pups (motor activity, FOB observation, neurobehavioral/neuropathological inspection, brain measurements, etc.) were observed at doses up to the highest dose of 750 mg/kg/day (ATSDR (2006), SIAR (2009)). (8) In several case-control study reports that investigated the relationship between maternal exposure to solvents containing this substance and adverse pregnancy outcomes (spontaneous abortion and/or congenital malformation), there was no clear evidence of an association between this substance itself and adverse pregnancy outcomes (ATSDR (2006)).
8	Specific target organ toxicity - Single exposure	Category 1 (cardiovascular system), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	[Rationale for the Classification] Based on (1) and (2), narcotic effects and cardiovascular system were adopted, respectively, and it was classified in Category 1 (cardiovascular system), and Category 3 (narcotic effects). Also, in the previous classification, respiratory tract irritation was adopted based on (3), however, since there were no findings indicating respiratory tract irritation in the original document, it was not adopted for classification. [Evidence Data] (1) The most important findings of acute inhalation exposure to this substance in humans were effects on the central nervous system. The severity of central nervous system depressant effects caused by poisoning from acute inhalation exposure increased as the exposure duration and level were increased. Impaired performance of psychophysiological function tests was observed in individuals exposed to moderate concentrations (at or above 175 ppm). Dizziness, lightheadedness and loss of coordination were caused by exposure to higher concentrations (at or above 500 ppm) and general anesthesia occurred at high levels (at or above 10,000 ppm) (ATSDR (2006), Patty (6th, 2012)). (2) After short-term inhalation of this substance at very high concentrations, severe cardiac arrhythmias and death may occur. Sensitization of the heart to endogenous epinephrine which is involved in the mechanism for the arrhythmias is considered to be also induced indirectly by this substance (ATSDR (2006)). [Reference Data, etc.] (3) In healthy volunteers exposed to this substance at a vapor concentration of 1.09 mg/L for 4 hours, increased concentrations of proinflammatory cytokines in nasal secretions and elevated olfactory threshold for n-butanol were observed. Therefore, this substance may act as a slight respiratory tract irritant (SIAR (2009), ATSDR (2006)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (central nervous system)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1 (central nervous system). No findings to identify target organs were obtained from animal studies. Based on the new information source, the classification result was changed. Based on (6), since the heart (chronic cardiac arrythmia) adopted in the previous classification was based on a specific case in which (cross) cardiac sensitization was developed only in two cases after halothane anesthesia, which was an acute effect, and the liver was reported only in one case in humans, they were excluded from target organs. [Evidence Data] (1) An epidemiological study reported that, in workers at a plant in Singapore exposed only to this substance, compared with unexposed workers from another plant, neurological effects including tiredness, inability to concentrate and impaired memory were observed (SIAR (2009)). (2) In a study of a group of 28 workers (average employment period: 17.6 years) with moderate to high exposure to concentrated liquid of this substance at a workplace having poor ventilation, the workers reported light-headedness, vertigo, nausea, and fatigue, and some workers fainted. Measures of coordination indicated that some workers exhibited deficits in balance and movement, and consistent, statistically significant deficits in memory, rhythm, and speed were seen (SIAR (2009), ATSDR (2006)). The workers had been exposed to not only this substance but also asbestos, silica, and/or concentrated alkali cleaning agents (SIAR (2009)). [Reference Data, etc.] (3) In a 13-week inhalation exposure test with rats and mice (vapor, 6 hours/day, 5 days/week) and a 2-year inhalation exposure test (vapor, 6 hours/day, 5 days/week), the only effect observed within the dose range for Category 1 and Category 2 was eosinophilic change in the olfactory epithelium of the nasal cavity observed at or above 200 ppm (1.09 mg/L, within the range for Category 2) in a 2-year inhalation exposure test with rats, and no similar findings were observed in mice (Results from preliminary Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (1998), Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare) (1998)). (4) In a 13-week oral toxicity study with rats and mice, the minimum dose at which effects were observed was a high dose of 2,820 to 4,800 mg/kg/day (SIAR (2009)). (5) Unlike (1) and (2), no neurological effect was reported to be observed in any epidemiological studies with workers (SIAR (2009)). (6) In human subjects with previous long-term exposure to this substance, chronic cardiac arrhythmia was reported to be developed in two cases after routine halothane anesthesia (SIAR (2009)). Also, in humans who ingested 600 mg/kg of this substance, elevated serum bilirubin levels (transaminase levels remained within normal limits), which was an effect on liver function, were reported to be observed in one case (ATSDR (2006)).
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)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 72-hour EbC50 = 0.536 mg/L for algae (Chlamydomonas reinhardtii) (AICIS IMAP, 2013, SIAR, 2009).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 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, METI, 1979)) and 17-day NOEC = 1.3 mg/L for crustacea (Daphnia magna) (AICIS IMAP, 2013, Environmental Risk Assessment for Chemical Substances Vol. 2 (Ministry of the Environment, 2003), SIAR, 2009). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained (crustacea, fish), then it is classified in Category 1 due to being not rapidly degradable and 72-hour EbC50 = 0.536 mg/L for algae (Chlamydomonas reinhardtii) (AICIS IMAP, 2013, SIAR, 2009). By drawing a comparison between the above results, it was classified in Category 1.
12	Hazardous to the ozone layer	Category 1	Warning	H420	P502	This substance is listed in the Annexes to the Montreal Protocol.

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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