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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	13463-39-3
Chemical Name	Nickel tetracarbonyl
Substance ID	R03-B-015-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	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	Category 2	Danger	H225	P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501	It was classified in Category 2 based on a flash point of < -20 deg C (closed cup), a boiling point of 43 deg C (GESTIS (Accessed June 2021). Besides, it is classified in Division 6.1, Subsidiary Risk 3, PG I in UNRTDG (UN1259).
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 estimated that it does not correspond to pyrophoric liquids, hazards of the highest precedence, because it is classified in Division 6.1 (3), PG I in UNRTDG (UN 1259). Therefore, it was classified as "Not classified."
10	Pyrophoric solids	Not classified (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 classified	- -	-	-	It contains metals (Ni), but it is estimated that it does not react vigorously with water from data obtained: water solubility of > 0.02 g/L (GESTIS (Accessed June 2021)).
13	Oxidizing liquids	Classification not possible	- -	-	-	It is an inorganic compound containing oxygen, but the classification is not possible due to no data.
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	It is an inorganic compound.
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to low-temperature-boiling liquids are not available.
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)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
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 1	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 1. Since the test concentration was lower than 90% (380,067 ppm) of the saturated vapor pressure, it was judged to be in a vapor state and classified based on the reference value in units of ppmV. [Evidence Data] (1) LC50 (0.5 hours) for rats: 240 mg/m3 (converted 4-hour equivalent value: 84.9 mg/m3 = 12.2 ppm) (CEPA PSAR (1994), EHC 108 (1991)) (2) LC50 (0.5 hours) for rats: 56 ppm (converted 4-hour equivalent value: 19.8 ppm) (US AEGL (2007)) (3) LC50 (0.5 hours) for rats: 33.6 ppm (converted 4-hour equivalent value: 11.9 ppm) (US AEGL (2007)) (4) LC50 (0.5 hours) for rats: 35 ppm (converted 4-hour equivalent value: 12.4 ppm) (ACGIH (2014)) (5) LC50 (0.5 hours, estimate) for humans: 3 ppm (converted 4-hour equivalent value: 1.06 ppm) (US AEGL (2007))
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	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Besides, in the previous classification, the findings about nickel chloride were used. In this classification, they were not used and the classification result was changed.
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Also, since the HSDB, which was adopted as a rationale for the previous classification, was currently not available, the classification result was changed.
4	Respiratory sensitization	Category 1A	Danger	H334	P304+P340 P342+P311 P261 P284 P501	[Rationale for the Classification] (1) Based on (1), it was classified in Category 1A in accordance with the GHS Classification Guidance for the Japanese Government. Also, based on the new findings, classification results were changed. [Evidence Data] (1) The Japan Society For Occupational Health classified this substance as nickel or its compounds in occupational sensitizers to the respiratory tract Group 2. [Reference Data, etc.] (2) It was reported that a chemical engineer, who had been exposed for a long period to low levels of nickel carbonyl, developed asthma and Loeffler's syndrome (EHC 108 (1991)).
4	Skin sensitization	Category 1A	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 1A in accordance with the GHS Classification Guidance for the Japanese Government. Also, based on the new findings, classification results were changed. [Evidence Data] (1) The Japan Society For Occupational Health classified this substance as nickel or its compounds in occupational sensitizers to the skin Group 1.
5	Germ cell mutagenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) It was reported that, as for in vivo, in a dominant lethal test on rats, negative results in inhalation exposure and positive results in intravenous administration were obtained (EHC 108 (1991)). (2) It was reported that, in 64 workers exposed to this substance over a period of 10 years, a significant increase in the incidence of chromosomal anomalies in peripheral blood lymphocytes was found compared to unexposed workers, and a significant increase in dyskaryotic cells was also found compared to unexposed workers in an examination of sputum. It was also reported that an increase in the incidence of chromosomal anomalies in peripheral blood lymphocytes taken from workers occupationally exposed to this substance was not observed but this substance appeared to act synergistically with cigarette smoke in increasing the frequency of sister chromatid exchange in peripheral blood lymphocytes (US AEGL (2007)). (3) Nickel compounds are not mutagenic in bacteria, and only weakly mutagenic in the cultured mammalian cells under standard test procedures, but can induce DNA damage, chromosomal aberrations, and micronuclei in vitro and in vivo. It has also been hypothesized that this substance may cause disturbances of DNA repair and epigenetic effects (altered DNA methylation patterns, etc.) (IARC 100C (2012)).
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 1A. [Evidence Data] (1) As for the classification results by domestic and international organizations, the IARC classified nickel and nickel compounds including this substance in Group 1 (IARC 100C (2012)), and the EPA classified this substance in B2 (IRIS (1987)), the ACGIH classified it in A3 (ACGIH (7th, 2014)), the EU classified it in Carc. 2 (EU-CLP Classification Results (Accessed July 2021)). (2) An elevated risk of lung cancer and nasal cavity cancer was observed among workers involved in a variety of nickel sulfide ore smelting and nickel refining processes that included high-temperature processing of nickel matte and nickel-copper matte, electrolytic refining, and Mond process refining. The exposures included metallic nickel, nickel oxides, nickel subsulfide, water-soluble nickel compounds and nickel carbonyl (IARC 110C (2012)). (3) In an epidemiological study in the U.K. on nickel carbonyl refinery workers, an elevated risk of lung cancer was observed among workers who had been employed for 20 years or more (IARC 110C (2012)). (4) There is sufficient evidence in humans for the carcinogenicity of mixtures that include nickel compounds and nickel metal. These substances cause cancers of the lung and of the nasal cavity and paranasal sinuses (IARC 110C (2012)). (5) It was reported that, in an inhalation exposure test for this substance with rats, although the test method did not meet today's standard, the rats developed pulmonary tumors (IRIS (1987), ACGIH (7th, 2014)). The IARC reported that there was limited evidence in experimental animals for carcinogenicity of this substance. In addition, it concluded that in view of the findings in a carcinogenicity test for overall nickel compounds, there was sufficient evidence in experimental animals for the carcinogenicity of nickel compounds (IARC 110C (2012)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 1B. Based on the new findings, classification results were changed. [Evidence Data] (1) It was reported that, in a developmental toxicity study with rats exposed by inhalation (one day from days 7 to 9 of gestation, for 15 minutes/day, 22.4 ppm), reduced litter size was observed in all dose groups and an increase in the number of fetuses having ocular malformations (day 7: 9/14, day 8: 9/13) was observed in the groups exposed on days 7 and 8 of gestation. Besides, in the group exposed on day 8 of gestation, deaths (2/15 rats) in parental animals were observed (US AEGL (2007), ACGIH (7th, 2014)). [Reference Data, etc.] (2) It was reported that, in a developmental toxicity study with hamsters exposed by inhalation (one day from days 4 to 8 of gestation, for 15 minutes/day, 8.4 ppm), increased incidences of malformations in fetuses (5.5 to 5.8%, 0% in the control group), an increase in the number of litters having malformed pups (24 to 33%, 0% in the control group), and increased incidences of serous cavity hemorrhage (18 to 25%, 0% in the control group) were observed in dams exposed on day 4 or 5 of gestation (US AEGL (2007)). (3) In a developmental toxicity study with hamsters exposed by inhalation (day 5 of gestation, for 15 minutes, 8.4 ppm), marked general toxicity effects (death (5/14 animals)) in parental animals and an increase in neonatal mortality by postpartum day 4 and increased incidences of serous cavity hemorrhage (peritoneal, pleural, pericardial, and subdural spaces) in fetuses were observed (US AEGL (2007)). (4) In the EU CLP, it was classified in Repr. 1B. (EU-CLP Classification Results (Accessed July 2021)).
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, respiratory organs, gastrointestinal tract, liver, kidney)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1 (central nervous system, respiratory organs, digestive tract, liver, kidney). Also, since details of the cardiovascular effects observed in (2) and the effects in (4) were unknown, they were not used for classification. Besides, the significant effects on the adrenal gland and spleen in the previous classification were not observed in (1) to (3) and they were not adopted as target organs. [Evidence Data] (1) It was reported that, in a case in which over 100 workers at a petroleum refining facility were exposed to this substance, 31 experienced acute symptoms of toxicity (headache, chest and epigastric pain, nausea, vomiting, chest constriction, shortness of breath, hacking and unproductive cough, extreme weakness, fatigue) and two among them died. Also, pneumonitis, respiratory difficulties (cough, shortness of breath, chest constriction) and neurological signs (convulsions, confusion) were associated with those individuals with severe or lethal poisoning (US AEGL (2007)). (2) It was reported that, in 179 cases of nonlethal occupational exposure to this substance, respiratory system, nervous system, digestive tract, and cardiovascular effects were observed. Besides, the analysis results of the toxic responses showed that the immediate phase was characterized by neurologic disorders and airway irritation, while the delayed phase was characterized by chest pain, cough, dyspnea, palpitation, fever, leukocytosis, and some X-ray abnormalities (irregular linear shadow, expansion and increased density of the hilus, diffuse irregular nodular mottling or patchy shadows) (US AEGL (2007), EHC 108 (1991)). (3) It was reported that, among 156 male workers exposed to this substance at a plant in Nagoya, 137 workers exhibited abnormal liver function, renal insufficiencies, skin lesions, abnormal densities in pulmonary x-rays, and symptoms of encephalopathy. Besides, no fatalities occurred, but due in part to treatment of the workers with Antabuse and Dithiocarb (US AEGL (2007)). [Reference Data, etc.] (4) In a case of poisoning with this substance in humans, apart from pulmonary lesions, degeneration of the liver, kidneys, adrenal glands and spleen were observed. In males who died, cerebral edema and punctate hemorrhages were observed (EHC 108 (1991)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (central nervous system, respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] For effects of repeated exposure to this substance, based on (1), the central nervous system, and based on (2), the respiratory organs were adopted as target organs, and this substance was classified in Category 1 (central nervous system, respiratory organs). It was classified based on the new information source. [Evidence Data] (1) It was reported that, in an epidemiological study in which serum monoamine oxidase (SMAO), which is an enzyme metabolizing and catabolizing monoamine neurotransmitters, and electroencephalograms were evaluated in male and female workers who had handled this substance for a long time, a significant decrease in SMAO activity and a significant increase in the incidence of abnormal electroencephalograms were observed in longer exposure groups (US AEGL (2007)). (2) In an epidemiological study of effects on lung functions in workers occupationally exposed to this substance for 2 to 20 years, significant alterations in several lung function parameter measurements were noted in men exposed for 14 years or more and for women exposed for more than 10 years, and it was suggested that long-term exposure to this substance may affect respiratory function but are not life threatening. Besides, in short-term exposure, there was no change in most parameters. The long-term exposure group included workers exposed for 18.6 years (men) and 16.6 years (women) on average and the short-term exposure group included workers exposed for 2.5 years (men) and 3.8 years (women) on average, and the average concentration of nickel carbonyl at the work area ranged from 0.007 to 0.52 mg/m3 (0.00098 to 0.072 ppm). Unexposed workers served as controls (US AEGL (2007), ACGIH (2014)).
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)	Classification not possible	- -	-	-	No data available.
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	No data available.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not 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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