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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	75-45-6
Chemical Name	Chlorodifluoromethane
Substance ID	H26-B-038, R-016
Classification year (FY)	FY2014
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	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)
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	- -	-	-	Gas (GHS definition)
2	Flammable gases (including chemically unstable gases)	Classification not possible	- -	-	-	Although there is data of an upper explosion limit of 26.9% (Matheson (2001)), there is no data of a lower explosion limit. Because it is not possible to select Category 1 or 2, the classification is not possible.
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified	- -	-	-	Because there is data of an upper explosion limit of 26.9% (Matheson (2001)), and it is combustible, it was classified as "Not classified."
5	Gases under pressure	Liquefied gas	Warning	H280	P410+P403	From a critical temperature (96.0 deg C (HSDB (Access on July 2014))) above +65 deg C, it was classified as liquefied gas (low pressure liquefied gas).
6	Flammable liquids	Not applicable	- -	-	-	Gas (GHS definition)
7	Flammable solids	Not applicable	- -	-	-	Gas (GHS definition)
8	Self-reactive substances and mixtures	Not applicable	- -	-	-	Gas (GHS definition)
9	Pyrophoric liquids	Not applicable	- -	-	-	Gas (GHS definition)
10	Pyrophoric solids	Not applicable	- -	-	-	Gas (GHS definition)
11	Self-heating substances and mixtures	Not applicable	- -	-	-	Gas (GHS definition)
12	Substances and mixtures which, in contact with water, emit flammable gases	Not applicable	- -	-	-	Gas (GHS definition)
13	Oxidizing liquids	Not applicable	- -	-	-	Gas (GHS definition)
14	Oxidizing solids	Not applicable	- -	-	-	Gas (GHS definition)
15	Organic peroxides	Not applicable	- -	-	-	Gas (GHS definition)
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to gas substances are not available.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Not applicable	- -	-	-	Gas (GHS definition)
1	Acute toxicity (Dermal)	Not applicable	- -	-	-	Gas (GHS definition)
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	Based on a report of an LC50 value (4 hours) of 219,000 ppm for rats (PATTY (6th, 2012), EU-RAR (2007), EHC 126 (1991)), it was classified as "Not classified." New information sources (PATTY (6th, 2012), EU-RAR (2007), EHC 126 (1991)) were added, and the text was revised.
1	Acute toxicity (Inhalation: Vapours)	Not applicable	- -	-	-	Gas (GHS definition)
1	Acute toxicity (Inhalation: Dusts and mists)	Not applicable	- -	-	-	Gas (GHS definition)
2	Skin corrosion/irritation	Not classified	- -	-	-	There is a report that slight irritation was observed in a skin irritation test in which 0.5 mL of this substance in liquid form was applied to rabbits for 24 hours (EU-RAR (2007)). It is described in EU-RAR (2007) that these results were due to tissue cooling by physical vaporization rather than due to irritation. From the above results, it was judged as "Not classified" (Category 3 in UN GHS classification). Besides, there is a report that redness and slight swelling of the skin were observed by repeated exposure to this substance of rats (6 weeks, 5 days/week, 2 times/day, 10 seconds each). The category was changed by adding information sources in List 1 and changing the GHS classification guidance for the Japanese Government.
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	There is a report that in an eye irritation test in which this substance in the form of the liquefied gas was sprayed to 6 rabbits for 5 or 30 seconds, although a slight chemosis and a slight redness were observed at 1 hour, they disappeared at 48 hours (EU-RAR (2007)). It is described in EU-RAR (2007) that this result did not meet the criteria for a classification as an irritant to the eyes, in this classification, however, the effects on the eyes by exposure to this substance were taken into account, it was classified in Category 2B.
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. Besides, although there is a report that it was negative in a sensitization test with guinea pigs (modified maximization method) (EHC 126 (1991), EU-RAR (2007)), since it was not a test according to the guideline and details such as the positive rate were unknown, it was not used in the determination of category.
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, it was all negative in dominant lethal tests with rats and mice, a mouse bone marrow micronucleus test, and chromosomal aberration tests with bone marrow cells of rats and mice (EU-RAR (2007), ECETOC JACC (1989), DFGOT vol. 3 (1992), EHC 126 (1991), IARC vol. 41 (1986), PATTY (6th, 2012), IUCLID (2000)). As for in vitro, it was positive or negative in bacterial reverse mutation tests, and it was negative in a mammalian cell gene mutation test and unscheduled DNA synthesis tests with human cells (OEL Documentations (Japan Society For Occupational Health (JSOH), 1987), EU-RAR (2007), ECETOC JACC (1989), EHC 126 (1991), IARC vol. 41 (1986), PATTY (6th, 2012), IUCLID (2000)). As above, although there were positive results in the in-vitro tests, it was negative in the in-vivo tests and therefore was judged not to be mutagenic in vivo.
6	Carcinogenicity	Classification not possible	- -	-	-	Since it was classified in Group 3 by IARC (IARC (1999)) and in A4 by ACGIH (ACGIH (7th, 2001)), it was classified as "Classification not possible."
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	There is a report that in a teratogenicity test with rats by the inhalation route, anophthalmia and microphthalmia, which are rare as a spontaneous malformation, were observed at a dose (1,000 ppm) where no general toxicity was observed in parental animals (EU-RAR (2007), IRIS (1993), DFGOT vol. 3 (1992), EHC 126 (1991)). Regarding this, a large replicate study consisting of 19 batches of teratogenicity test trials was performed at another test facility, and its results were compared with historical controls in the 10 year period following the test. As a result, in the replicate study, at a dose (50,000 ppm) where a slight maternal toxicity (decreased body weight gain) was observed, significant specific malformations (anophthalmia, complications of anophthalmia and microphthalmia) with a low incidence were observed, and the relationship with maternal toxicity was considered to be low. In addition, in comparison with background data, there is a report that the incidence of anophthalmia in the large study was higher than in the historical controls and the incidence of the complications of anophthalmia and microphthalmia was comparable to the upper limit of the historical controls (EU-RAR (2007)). It is stated in EU-RAR (2007) that since the incidence of specific malformations was low, and they were observed at doses where slight maternal toxicity was observed, this could justify a classification of this substance in Category 3 (harmful for reproduction), R63. On the other hand, it is described in PATTY (6th, 2012) that although it seemed to be exposure-related since it was observed in multiple studies with rats, the low incidence at the high dose suggested that it is a very weak response and may be only indirectly related to the exposure. From the above, by examining the significance of the evidence for classification, by which this substance was classified in Category 1B in the previous classification, although its relevance to exposure could not be denied, its incidence was very low and therefore, it was reasonable to classify it in Category 2, and the classification was changed from Category 1B to Category 2.
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, 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	In humans, arrhythmia, shortness of breath, confusion, loss of consciousness and lethargy by inhalation exposure, and at very high concentrations, cardiovascular disorders and central nervous system depression occurred. In accidental cases, dark red blood, congestion, edema, hemorrhage, and emphysema of the lung, pigment-laden macrophages in the alveoli and fatty droplets of hepatocytes were reported at autopsy (Environmental Risk Assessment for Chemical Substances Vol.5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), EU-RAR (2007), EHC 126 (1991)). In addition, as for this substance, weak narcotic effects were reported (OEL Documentations (Japan Society For Occupational Health (JSOH), 1987)). As for experimental animals, central nervous system depression and asphyxiation (no animal species described) (ACGIH (7th, 2001)), narcotic effects, tremors, convulsions, narcosis, shallow respiration, respiratory depression in rats, incoordination, asphyxiation, and other signs of central nervous system depression such as loss of balance and respiratory distress in rabbits, depression of myocardial contractility, a drop in blood pressure, increased pulmonary resistance and decreased respiratory volume in monkeys, cardiac arrhythmia and increased sensitivity to adrenaline-induced arrhythmia in mice and cats, decreases in heart rate, myocardial contractility and carotid pressure, and arterial hypotension in rats, and cardiac sensitization in dogs were reported (OEL Documentations (Japan Society For Occupational Health (JSOH), 1987), DFGOT vol. 3 (1992), EU-RAR (2007), ECETOC JACC (1989), EHC 126 (1991), EU-RAR (2007), HSDB (Access on June 2014)). These findings in experimental animals were within the range of guidance values exceeding Category 2. From the above, based on the findings in humans, it was classified in Category 1 (central nervous system, cardiovascular system), Category 3 (narcotic effects). Besides, although fatty droplets in the liver were reported in human cases, it was judged that they could not be generalized since they were found in fatal cases. Therefore, it was not used in the classification. In addition, the findings in the lungs were not used in the classification because these findings were in fatal cases.
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	One of research workers in a pathology laboratory exposed to this substance during the preparation of frozen sections died from myocardial infarction, and following his death, others complained of excess palpitation. Although it was reported that there was an association between exposure to this substance and palpitations in a survey, no comparable control group was examined, and reporting of symptom memories was subjective. Therefore, it was judged to be of low reliability (EU-RAR (2007)). In addition, in an epidemiological survey on refrigeration repair workers exposed to chlorofluorocarbon compounds including this substance, there is a study report that although chest X-ray, pulmonary function tests, electrocardiogram, and blood and urine tests showed no abnormalities, lightheadedness and palpitations were more common in the refrigeration workers than in the unexposed controls. However, the EU concluded that the study design was inadequate, and no conclusions could be drawn from this report (EU-RAR (2007)). That is, in humans, there were no hazardous findings available clearly related with exposure to this substance. As for experimental animals, in tests in which mice and rats were exposed to this substance by inhalation for 83-94 weeks and 117-131 weeks, respectively, only slight effects such as hyperactivity (mice) and decreased body weight gain (rats) were observed at a high concentration of 50,000 ppm. Based on these results, the NOAEL for this substance was set to be 10,000 ppm (EU-RAR (2007), IRIS (1992), Environmental Risk Assessment for Chemical Substances Vol.5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006)). This substance is a gas, and it was considered to be classified as "Not classified" from the test results in experimental animals because the inhalation route was the main exposure route. However, it is considered that there were inadequate findings to draw a conclusion on the presence or absence of effects by repeated inhalation exposure in humans and that the situation remained unclear. Therefore, it was classified as "Classification not possible."
10	Aspiration hazard	Not applicable	- -	-	-	Gas (GHS definition)

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)	Not classified	- -	-	-	It was classified as "Not classified" from 48-hour EC50 = 433 mg/L for crustacea (Daphnia magna), 96-hour LC50 = 777 mg/L for fish (Danio rerio) (both EU-RAR, 2007).
11	Hazardous to the aquatic environment (Long-term)	Not classified	- -	-	-	Reliable chronic toxicity data were not obtained. Because it corresponds to "Not classified" in acute toxicity for crustacea and fish and is not water-insoluble (water solubility = 2700 mg/L, PHYSPROP Database, 2009), it was classified as "Not classified."
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.

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