GHS Classification Result

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GENERAL INFORMATION
Item Information
CAS RN 67-66-3
Chemical Name Chloroform
Substance ID H27-B-050/C-086B_P
Classification year (FY) FY2015
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 FY2014   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
-
-
- - It is not combustible (ISCS (2004)).
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 not combustible (ISCS (2004)).
10 Pyrophoric solids Not applicable
-
-
- - Liquid (GHS definition)
11 Self-heating substances and mixtures Not classified
-
-
- - It is not combustible (ISCS (2004)).
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
As LD50 values for rats, there are 12 reports within a range of 440-2,440 mg/kg. It was classified in Category 4 to which the largest number of data (8 cases) corresponded (695 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.2 (Ministry of the Environment, 2003)), 908 mg/kg (male), 1,117 mg/kg (female) (Hazard Assessment Report (CERI, NITE, 2008), DFGOT Vol. 14 (2000), ATSDR (1997), EHC 163 (1994)), 440 mg/kg (14-day-old), 1,300 mg/kg (young adults), 1,200 mg/kg (elder adults) (Hazard Assessment Report (CERI, NITE, 2008), IARC 73 (1999), ATSDR (1997), EHC 163 (1994)), 1,970 mg/kg (male) (JECFA FAS 14), 2,000 mg/kg (male) (Hazard Assessment Report (CERI, NITE, 2008), DFGOT Vol. 14 (2000), ATSDR (1997), EHC 163 (1994))).
1 Acute toxicity (Dermal) Not classified
-
-
- - Based on a report that there was no death from administration in rabbits at 3,980 mg/kg (EU-RAR (2007), DFGOT Vol. 14 (2000)), it was classified as "Not classified." New information was added, and the category was revised.
1 Acute toxicity (Inhalation: Gases) Not applicable
-
-
- - Liquid (GHS definition)
1 Acute toxicity (Inhalation: Vapours) Category 4


Warning
H332 P304+P340
P261
P271
P312
Based on reports of LC50 values (4 hours) for rats of 9,770 ppm (ATSDR (1997)) and 9,636 ppm (Environmental Risk Assessment for Chemical Substances Vol.2 (Ministry of the Environment, 2003)), it was classified in Category 4. Besides, since the LC50 values were lower than 90% of the saturated vapor pressure concentration (259,211 ppm), a reference value in the unit of ppm was applied as vapour without mist. New information was added, and the category was revised.
1 Acute toxicity (Inhalation: Dusts and mists) Classification not possible
-
-
- - 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
There are reports from skin irritation tests with rabbits that as a result of a 24-hour application of an undiluted solution of this substance to abdominal skin, mild hyperemia, moderate necrosis, and eschar formation were observed (EHC 163 (1994), Hazard Assessment Report (CERI, NITE, 2008)), and that severe irritation was observed by an application of an undiluted solution of this substance (DFG Vol.14 (2000)). In addition, there is a report that as a result of an application of this substance 1-4 times to rabbit ears, slight hyperemia and epidermolysis were observed (EHC 163 (1994), Hazard Assessment Report (CERI, NITE, 2008)). There is a description that this substance is irritating to the skin (OEL Documentations (Japan Society For Occupational Health (JSOH), 2005), CICAD 58 (2004)). From the above, it was classified in Category 2. Besides, this substance was classified as "Skin. Irrit. 2 H315" in EU CLP classification (ECHA CL Inventory (Access on September 2015)). The category was changed because there was no information on irreversible effects.
3 Serious eye damage/eye irritation Category 1


Danger
H318 P305+P351+P338
P280
P310
There is a report that in an eye irritation test with rabbits, as a result of an application of this substance, severe irritation with mydriasis, keratitis and corneal opacity was observed, and the symptoms resolved in 2-3 weeks for 4 animals, but the symptom of corneal opacity persisted even after 3 weeks in one (EHC 163 (1994)). In addition, there is a report that slight irritation of the conjunctiva and corneal injury were observed (EHC 163 (1994), Hazard Assessment Report (CERI, NITE, 2008)), and a description that this substance was irritating to the eyes (OEL Documentations (Japan Society For Occupational Health (JSOH), 2005), CICAD 58 (2004)). From the above, since the symptom did not completely resolve 3 weeks after administration, it was classified in Category 1. Besides, this substance was classified as "Eye. Irrit. 2 H319" in EU CLP classification (ECHA CL Inventory (Access on September 2015)).
4 Respiratory sensitization Classification not possible
-
-
- - Classification not possible due to lack of data.
4 Skin sensitization Classification not possible
-
-
- - Classification not possible due to lack of data.
5 Germ cell mutagenicity Category 2


Warning
H341 P308+P313
P201
P202
P280
P405
P501
As for in vivo, a gene mutation test with the liver of transgenic mice was negative, micronucleus tests with liver and kidney cells of rats and a mouse bone marrow micronucleus test gave positive or negative results, chromosomal aberration tests with bone marrow cells of rats, mice and hamsters were approximately positive, sister chromatid exchange tests with mouse bone marrow cells were positive and negative results, a DNA breakage test with the kidney of rats was negative, DNA binding (DNA adduct) tests with the liver and kidney of rats and mice gave weakly positive and negative results, unscheduled DNA synthesis tests with the liver of rats and mice were negative, and DNA repair tests with the liver and kidney of mice were negative (Hazard Assessment Report (CERI, NITE, 2008), EU-RAR (2007), CICAD 58 (2004), DFGOT Vol. 14 (2000), IARC 73 (1999), CEPA (2001), ATSDR (1997)). As for in vitro, bacterial reverse mutation tests gave positive or negative results, a gene mutation test and a mouse lymphoma test with mammalian cultured cells gave positive or negative results, a chromosomal aberration test was negative, sister chromatid exchange tests gave positive or negative results, and an unscheduled DNA synthesis test was negative (Hazard Assessment Report (CERI, NITE, 2008), EU-RAR (2007), DFGOT Vol. 14 (2000), IARC 73 (1999), ATSDR (1997), CEPA (2001)). From the above, there were positive results in in-vivo somatic cell mutagenicity tests, and it was classified in Category 2 according to the GHS classification guidance for the Japanese government.
6 Carcinogenicity Category 2


Warning
H351 P308+P313
P201
P202
P280
P405
P501
As for humans, in epidemiological studies on oral exposure to this substance via drinking water, there are case reports on an excessive risk of multi-site cancers, especially urinary bladder cancers and colorectal cancers. However, the possibility of effects from the by-product, trihalomethane, is high, and in reports on carcinogenic effects due to inhalation exposure to this substance in the workplace, power by statistical analysis was low, and it was pointed out that the reliability was doubtful for an excess risk of prostate cancer and lung cancer. Based on the above, IARC concluded that there was inadequate evidence in humans for carcinogenicity with this substance (IARC 73 (1999)).
On the other hand, as for experimental animals, by pointing out that in 3 tests with mice by the oral route and one test with mice by the inhalation route, renal tubule tumors were observed, hepatocellular tumors were also observed in one test, and renal tubule tumors were observed in 3 tests with rats by the oral route, IARC concluded that there was sufficient evidence for carcinogenicity in experimental animals and classified it in Group 2B in 1999 (IARC 73 (1999)). As for the classification of carcinogenicity of this substance by other organizations, ACGIH classified it in A3 (ACGIH (7th, 2001)), Japan Society For Occupational Health (JSOH) in 2B (Recommendation of Occupational Exposure Limits (2015)), EU in Carc. 2 (EU-RAR (2007)), EPA as "L (Likely to be carcinogenic to humans)" under high-exposure conditions that lead to cytotoxicity and regenerative hyperplasia and as "NL (Not likely to be carcinogenic to humans)" under other conditions in 1988 classification (IRIS Summary (Access on August 2015)), and NTP as R (NTP RoC (13th, 2014)), respectively.
From the above, the classification results by other organizations including IARC are almost consistent, therefore, it was classified in Category 2 for this hazard class.
7 Reproductive toxicity Category 2


Warning
H361 P308+P313
P201
P202
P280
P405
P501
As for humans, it is described that an association between occupational exposure to this substance and an increased risk of spontaneous abortions was reported, but this was a situation involving simultaneous exposure to other solvents (IRIS Tox Review (2001)). In addition, there is a report that a correlation was found between the concentration of this substance and inhibition of intrauterine growth of fetuses due to oral exposure to this substance via drinking water, but the possibility of effects by trihalomethane which was generated by chlorine disinfection, was pointed out (IRIS Tox Review (2001)). As above, there was no reliable information on adverse effects on human fertility specifically due to exposure to this substance.
As for experimental animals, there is a description that in a multigeneration reproductive test with mice by the oral route (drinking water), in the F1 and F2 generation animals of the high dose group, there was a significant decrease in the breeding index (a decrease in pregnancy index, a decrease in number of litters, a decrease in birth rate) as well as decreased body weight gain and a survival rate (DFGOT Vol. 14 (2000), Hazard Assessment Report (CERI, NITE, 2008)). On the other hand, as for developmental toxicity effects, in a developmental toxicity test with pregnant rats exposed by inhalation during the organogenesis period (gestational day 6-15), in rats, an increased incidence of malformations (tailless, anal atresia, missing ribs), as well as low values of fetal body weight and craniocaudal length, skeletal variations (delayed ossification, wavy ribs), and subcutaneous edema was observed in fetuses at the doses (30, 95 ppm) where maternal toxicity was manifested (DFGOT Vol. 14 (2000), CICAD 58 (2004), Hazard Assessment Report (CERI, NITE, 2008)). In addition, there is a description that also in a test in which pregnant mice were exposed by inhalation at 100 ppm during the organogenesis period (gestational day 8-15), decreased body weight gain and a slight decrease in a pregnancy rate in maternal animals, and an increase in the incidence of cleft palate as a malformation as well as fetotoxicity (low values of fetal body weight and craniocaudal length, delayed ossification) in the fetuses were observed (DFGOT Vol. 14 (2000), Hazard Assessment Report (CERI, NITE, 2008)). Besides, it is reported that in developmental toxicity tests with pregnant rats or pregnant rabbits dosed by gavage during the organogenesis period, fetotoxicity was slight (only a low value of fetal body weight or delayed ossification) or no effect was found even at the doses where maternal toxicity was manifested (DFGOT Vol. 14 (2000), CICAD 58 (2004), Hazard Assessment Report (CERI, NITE, 2008)).
From the above, since in the inhalation route, developmental toxicity effects including malformations were observed at the doses where maternal toxicity was manifested in experimental animals, it was classified in Category 2 for this hazard class.
8 Specific target organ toxicity - Single exposure Category 1 (respiratory organs, cardiovascular system, liver, kidney), Category 3 (narcotic effects)



Danger
Warning
H370
H336
P308+P311
P260
P264
P270
P321
P405
P501
P304+P340
P403+P233
P261
P271
P312
This substance is irritating to the respiratory tract (EU-RAR (2007)). There are multiple acute toxicity data both in humans and in experimental animals. As for humans, there is a history that the substance was used as an anesthetic. Narcotic effects, cough, dizziness, lethargy, hypoesthesia, headache, nausea, vomiting, abdominal pain, weakness, unconsciousness, coma, convulsive seizures, rapid respiration, respiration center paralysis, consciousness disturbed, acute respiratory failure, cardiac arrhythmia, cardiovascular system depression effect, ventricular fibrillation, jaundice, hepatocellular degeneration and necrosis, renal tubular necrosis, and renal failure by inhalation exposure, and abdominal pain, nausea, vomiting, diarrhea, gastrointestinal tract irritation, respiration center paralysis, convulsive seizures, coma, oliguria, albuminuria, kidney damage, swelling, hyaline and fatty degeneration of the renal tubule epithelium, liver damage, and hepatocyte necrosis by oral ingestion were reported (Hazard Assessment Report (CERI, NITE, 2008), DFGOT Vol. 14 (2000), IARC 73 (1999), Environmental Risk Assessment for Chemical Substances Vol.2 (Ministry of the Environment, 2003), PATTY (6th, 2012), OEL Documentations (Japan Society For Occupational Health (JSOH), 2005), EU-RAR (2007), CICAD 58 (2004), ATSDR (1997), ACGIH (7th, 2001), IPCS, PIM 121 (1993)).
As for experimental animals, in oral administration in rats and mice (corresponding to Category 1), incoordination, sedation, narcotic effects, centrilobular fatty infiltration and necrosis of the liver, centrilobular hepatocytes necrosis, regenerative proliferation of the proximal tubular epithelial cells of the renal cortex, cell proliferation of the kidney, and severe necrosis in the kidney were reported. In inhalation exposure in rats and mice (corresponding to Category 1), narcotic effects, fatty infiltration of the liver, hepatocyte necrosis, necrosis of the renal proximal and distal tubules, and calcification of the renal cortex were reported. In dermal administration in rabbits (corresponding to Category 1), renal tubular degeneration was observed (Hazard Assessment Report (CERI, NITE, 2008), DFGOT Vol. 14 (2000), IARC 73 (1999), OEL Documentations (Japan Society For Occupational Health (JSOH), 2005), EU-RAR (2007), CICAD 58 (2004), DFGOT Vol. 14 (2000), ATSDR (1997), ACGIH (7th, 2001), PATTY (6th, 2012), CEPA (2001)).
From the above, since this substance affects the respiratory organs, cardiovascular system, liver, and kidney in addition to respiratory tract irritation and narcotic effects, it was classified in Category 1 (respiratory organs, cardiovascular system, liver, kidney), and Category 3 (narcotic effects).
9 Specific target organ toxicity - Repeated exposure Category 1 (central nervous system, respiratory organs, liver, kidney)


Danger
H372 P260
P264
P270
P314
P501
As for humans, there is a description that all 13 workers exposed to chloroform at a concentration of approximately 1,950 mg/m3 for up to 6 months showed jaundice, and 1-2.9 mg/L blood chloroform was detected in 5 of them (DFGOT Vol. 14 (2000)). There is a description that jaundice was observed in 18 workers who were exposed to chloroform at concentrations of 80-160 mg/m3 for 4 months or more in another factory (DFGOT Vol. 14 (2000)). In addition, there is a description that in workers exposed to chloroform at 14-400 ppm (68-1,950 mg/m3) for 1-6 months, symptoms such as development of hepatitis, jaundice, nausea and vomiting were observed, and the development of hepatitis occurred even at exposure concentrations of 2-205 ppm (9.7-1,000 mg/m3) (PATTY (6th, 2012)). Moreover, there is a description that 17 out of 68 workers exposed to 10-1,000 mg/m3 of chloroform in a pharmaceutical plant for 1-4 years were diagnosed with hepatomegaly. It is also described that hepatitis in 3 of them, fatty liver in 14, splenomegaly in 10 were seen (Environmental Risk Assessment for Chemical Substances Vol.2 (Ministry of the Environment, 2003)).
As for experimental animals, in tests in which mice were dosed by gavage or drinking water for 13 weeks, and a test in which rats were dosed by gavage for 3 weeks, at doses corresponding to Category 2 (converted guidance value: 14.8-60 mg/kg/day), effects on the liver (enlargement, degeneration and fatty change of hepatocytes, early hepatic cirrhosis like change, etc.), kidney (chronic inflammation, degeneration and necrosis of the proximal tubules, etc.), spleen (atrophy of the white pulp, a decrease in the number of antibody-forming cells) were observed. In addition, also in a test in which dogs were dosed by gavage via capsules for 7.5 years, an increased serum ALT value in addition to fatty change of the liver was observed at 15 mg/kg/day (converted guidance value: 12.9 mg/kg/day) (Hazard Assessment Report (CERI, NITE, 2008), Environmental Risk Assessment for Chemical Substances Vol.2 (Ministry of the Environment, 2003)). Moreover, in the inhalation route, in multiple tests in which rats and mice were exposed by inhalation (estimated as vapour) for 13 weeks or 2 years, from the concentrations corresponding to Category 1 (converted guidance value: 0.01-0.106 mg/L/6 hr/day), the same tissue changes as the above were observed in the liver and kidney, in addition, effects on the nasal cavity (bone hypertrophy, atrophy and metaplasia of the olfactory epithelium, eosinophilic changes in the olfactory epithelia and respiratory epithelia) were also observed (Hazard Assessment Report (CERI, NITE, 2008), OEL Documentations (Japan Society For Occupational Health (JSOH), 2005)).
From the above, the central nervous system (nausea, vomiting) and liver were considered as the target organs from the human findings, and the respiratory organs, liver, and kidney were considered as the target organs from the findings in experimental animals. Therefore, it was classified in Category 1 (central nervous system, respiratory organs, liver, kidney). Besides, as for the spleen, since there were little findings in humans, and the possibility of secondary effects due to severe hepatotoxicity such as cirrhosis could not be denied, it was excluded from the target organs.
10 Aspiration hazard Classification not possible
-
-
- - 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 3
-
-
H402 P273
P501
From 72-hour EC50 = 13.3 mg/L for algae (Chlamydomonas reinhardtii) (ECETOC TR91, 2003, CICAD 58, 2004, EU-RAR, 2007), it was classified in Category 3.
11 Hazardous to the aquatic environment (Long-term) Category 1


Warning
H410 P273
P391
P501
If chronic toxicity data are used, then it is classified in Category 1 due to being not rapidly degradable (a degradation rate by 14-day BOD = 0%, a degradation rate by GC = 4.6%, non-biodegradable (Official Bulletin of Ministry of International Trade and Industry, 1980)), and 21-day NOEC = 0.059 mg/L for fish (Oncorhynchus mykiss) (Environmental Risk Assessment for Chemical Substances vol. 2 (Ministry of the Environment, 2003)).
If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 3 due to being not rapidly degradable and 72-hour EC50 = 13.3 mg/L for algae (Chlamydomonas reinhardtii) (ECETOC TR91, 2003, CICAD 58, 2004, EU-RAR, 2007).
By drawing a comparison between the above results, it was classified in Category 1.
12 Hazardous to the ozone layer Classification not possible
-
-
- - No data available.


NOTE:
* A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted.
* Hazard_statement_and/or_Precautionary_statement will show when hovering the mouse over a code of Hazard_statement_and/or_Precautionary_statement.
Hazard_statement_and/or_Precautionary_statement are also provided in the Excel file.
* Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government,
and is intended to provide a reference for preparing GHS labelling and SDS for users.
* This is a provisional English translation of classification results and is subject to revision without notice.
* The responsibility for any resulting GHS labelling and SDS referenced from this site is with users.
* Codes assigned to each of the hazard statements and codes for each of the precautionary statement are
based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations.

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