NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	12035-72-2
Chemical Name	Nickel sulfide (synonym: Trinickel disulfide)
Substance ID	R03-B-011-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	FY2009
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)	- -	-	-	Solid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
7	Flammable solids	Not classified	- -	-	-	It is not combustible (GESTIS (Accessed June 2021)).
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 (Not applicable)	- -	-	-	Solid (GHS definition)
10	Pyrophoric solids	Not classified	- -	-	-	It is not combustible (GESTIS (Accessed June 2021)).
11	Self-heating substances and mixtures	Not classified	- -	-	-	It is not combustible (GESTIS (Accessed June 2021)).
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified	- -	-	-	It contains a metal (Ni), but it is estimated that it does not react vigorously with water from information that it is insoluble in water (GESTIS (Accessed June 2021)).
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Inorganic compounds containing no oxygen or halogen atoms.
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	It is an inorganic compound.
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances 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)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: > 5,000 mg/kg (EFSA (2015), Hazard Assessment Report (CERI, NITE, 2008)) (2) LD50 for rats (crystalline, amorphous): > 5,000 mg/kg (EFSA (2015)) (3) LD50 for rats: > 11,000 mg/kg (OECD TG 425, GLP) (EFSA (2015), REACH registration dossier (Accessed July 2021))
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] Solid (GHS definition). It was classified as "Not classified."
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)	Category 3	Danger	H331	P304+P340 P403+P233 P261 P271 P311 P321 P405 P501	[Rationale for the Classification] Based on (1), the data on females, in which highly harmful effects were observed, was adopted and it was classified in Category 3. Also, based on the new findings, classification results were changed. [Evidence Data] (1) LC50 (4 hours) for rats: 1.138 mg/L (males: 1.352 mg/L, females: 0.924 mg/L) (OECD TG 403, GLP) (CLH Report (2017), REACH registration dossier (Accessed July 2021))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Also, based on the new findings, classification results were changed. [Evidence Data] (1) In an acute dermal irritation/corrosion test with rabbits (n=3) (OECD TG 404, GLP, semiocclusive, 4-hour application, observation for 72 hours), slight erythema was observed in two animals but it was fully reversible within 72 hours. It was reported that no edema was observed in any animals and the primary dermal irritation index (PDII) was 0.3 (erythema/eschar score: 0.7/0/0, edema score: 0/0/0) (REACH registration dossier (Accessed Aug. 2021)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Also, based on the new findings, classification results were changed. [Evidence Data] (1) It was reported that, in an acute eye irritation/corrosion test with rabbits (n=3) (OECD TG 405, GLP, observation for 72 hours), corneal opacity, iritis, and conjunctivitis were observed in all animals one hour after application but disappeared within 72 hours (corneal opacity score: 0.7/0/0.3, iritis score: 0.3/0.3/0.3, conjunctival redness score: 1/0.7/0.3, chemosis score: 0/0/0) (REACH registration dossier (Accessed Aug. 2021)).
4	Respiratory sensitization	Category 1A	Danger	H334	P304+P340 P342+P311 P261 P284 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1A in accordance with the GHS Classification Guidance for the Japanese Government. Also, the classification result was changed in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) In the DFG MAK, it was classified in Sah (sensitization of respiratory tract and skin) (DFG MAK (2006)). (2) The Japan Society for Occupational Health classified this substance as nickel itself or its compounds in occupational sensitizers to the respiratory tracｔ Group 2 (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH) (FY2021)).
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) and (2), it was classified in Category 1A in accordance with the GHS Classification Guidance for the Japanese Government. Also, the classification result was changed in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) In the DFG MAK, it was classified in Sah (sensitization of respiratory tract and skin) (DFG MAK (2006)). (2) The Japan Society for Occupational Health classified this substance as nickel itself or its compounds in occupational sensitizers to the skin Group 1 (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH) (FY2021)). [Reference Data, etc.] (3) In the EU CLP CLH, it was classified in Skin Sens. 1.
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. Based on the new information source, classification results were changed. [Evidence Data] (1) It was reported that, as for in vivo, positive results in a micronucleus test using the bone marrow cells of mice (single intraperitoneal injection), negative results in a comet assay using nasal mucosa and lung tissue of mice and rats (inhalation exposure), negative results in a micronucleus test using the peripheral blood of mice (inhalation exposure), and positive results (DNA strand breaks) in a comet assay using nasal mucosa of genetically-modified mice (LacZ transgenic CD2F1) (inhalation exposure) were observed (EFSA (2015), REACH registration dossier (Accessed July 2021)). (2) It was reported that, as for in vitro, negative or uncertain results in a bacterial reverse mutation test, positive results (partially negative or unclear) in a gene mutation study using cultured mammalian cells, and positive results in a chromosomal aberration test using the human lymphocytes were observed (EFSA (2015), REACH registration dossier (Accessed July 2021), ECHA OEL Proposal (2017)). [Reference Data, etc.] (3) Nickel compounds are not directly mutagenic but there is a hypothesis that they induce genotoxic effects via different indirect mechanisms (oxidative stress, inhibition of DNA repair systems, epigenetic mechanism) (ECHA RAC Opinion on OEL Proposal (2018)). (4) It is considered that chronic inflammation is likely to play a significant role in nickel-induced carcinogenicity together with indirect genotoxicity (ECHA RAC Opinion on OEL Proposal (2018)). (5) In the EU, it was classified in Muta. 2 (EU-CLP Classification Results (Accessed July 2021)).
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1A. [Evidence Data] (1) As for the classification results by domestic and international organizations, the IARC classified nickel compounds (including this substance) in Group 1 (IARC 100C (2012)), the NTP classified them in K (NTP RoC 15th. (2021)) and the EPA classified this substance in A (Human Carcinogen) (IRIS (1987)), the ACGIH classified it in A1 (ACGIH (7th, 2001)), the EU classified it in Carc. 1A (CLP Classification Results (Accessed July 2021)), and the DFG classified it in Category 1 (DFG MAK (2006)). (2) In a 2-year inhalation exposure test with rats (6 hours/day, 5 days/week), an increase in the incidence of lung neoplasms in males and females (bronchiolar/alveolar cell adenoma, carcinoma and adenoma or carcinoma (combined) in males, bronchiolar/alveolar cell carcinoma and bronchiolar/alveolar cell adenoma or carcinoma (combined) in females) and an increase in the incidence of pheochromocytoma of the adrenal medulla (benign, malignant and benign or malignant (combined) in males, benign in females) were observed. It was concluded that clear evidence of carcinogenicity was obtained in both males and females (NTP TR453 (1996), IARC 100C (2012)). (3) Epidemiological studies have provided evidence for lung cancer related to specific nickel compounds or classes of compounds (based, for example, on water solubility). Evidence for elevated risk of lung cancer in humans was demonstrated specifically for water-soluble nickel compounds in general such as nickel chloride and nickel sulfate, insoluble nickel compounds such as nickel oxides and nickel sulfides, and mostly insoluble nickel compounds (IARC 100C (2012)). [Reference Data, etc.] (4) A 2-year inhalation exposure test with mice in (2) did not show evidence of carcinogenicity in either males or females (NTP TR453 (1996), IARC 100C (2012)). (5) The Working Group of the IARC concluded that there was an elevated risk of lung and nasal sinus cancer among nickel refinery workers and they also found out that there was an elevation in lung cancer risk among nickel smelter workers (IARC 100C (2012)). (6) The US EPA has determined that this substance and dust generated in the nickel refinery process are human carcinogens (ATSDR (2005)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 2. [Evidence Data] (1) Although there was no report on human cases or epidemiological surveys, the Japan Society for Occupational Health classified nickel and nickel compounds (including insoluble nickel compounds) in Reproductive toxicant Group 3 because, in an oral administration of nickel chloride (water soluble) to pregnant rats, an increase in the number of dams that were delivered of stillborn pups and an increase in the number pups that died were observed under the conditions in which maternal toxicity was observed (OEL Documentations (Reproductive toxicant classification) (Japan Society For Occupational Health (JSOH)), 2014)). [Reference Data, etc.] (2) In a test by intramuscular injection to rats (day 6 of gestation, 20 mg/rat, single injection), F1 pups were observed throughout their life (for approximately 26 months), and as a result, the body weight of progeny of treated dams was lower than progeny of control dams but no effects on litter size, the development of congenital malformations, and progeny mortality rates were observed (REACH registration dossier (Accessed July 2021)). (3) An epidemiological study with humans exposed to nickel by inhalation did not show any indication of reproductive/developmental effects. Several animal data show that nickel can be considered as developmental toxicant. Water-soluble nickel compounds (nickel chloride, nickel sulfate, etc.) have been classified in Repr. 1B under the CLP Classification (ECHA OEL Proposal (2017)).
8	Specific target organ toxicity - Single exposure	Category 2 (respiratory organs)	Warning	H371	P308+P311 P260 P264 P270 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 2 (respiratory organs) since the effects on the respiratory organs (abnormal respiration) observed within the dose range for Category 2 were considered to be caused by inflammatory changes of the lungs. Also, based on the new findings, classification results were changed. [Evidence Data] (1) It was reported that, in an acute inhalation (dust) toxicity study with rats (OECD TG 403, GLP), at or above 1.02 mg/L (within the range for Category 2), clinical signs including facial staining, irregular respiration, hypoactivity, a thin appearance, reduced fecal volume, and cold limbs were observed, and one male and 3 females died; and at 5.15 mg/L (in the range corresponding to "Not classified"), clinical signs including abnormal respiration, hunched posture, and reduced food consumption were observed, and all animals died (CLH Report (2017)). [Reference Data, etc.] (2) It was reported that, after a single administration of this substance to rats via intratracheal instillation, multifocal pulmonary alveolitis with Type II alveolar cell hypertrophy were observed on day 7 (CLH Report (2017), Patty (2012)). (3) It was reported that, after a single administration of this substance to mice via intratracheal instillation, acute changes in the form of pulmonary hemorrhage were observed, and after a lapse of 20 hours to 7 days, an increased number of cells with nuclei of irregular shapes in the rinsings from lungs were observed (Patty (2012)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 1 (respiratory organs). [Evidence Data] (1) There are case reports stating that, among nickel refinery workers and nickel plating workers, rhinitis, sinusitis, nasal septum perforation, and dysplasia of nasal mucosa were observed. It is also said that workers exposed to nickel oxides and metal nickel at the concentrations of 0.04 mg/m3 or above for a long time have a higher probability of dying from respiratory diseases (OEL Documentations (Japan Society For Occupational Health (JSOH), 2009)). (2) It was reported that, in a 13-week inhalation exposure test with rats (6 hours/day, 5 days/week), at 0.15 to 2.5 mg/m3 (converted guidance value: 0.00011 to 0.0018 mg/L, within the range for Category 1), effects on the lung (increases in absolute and relative weight, an increase in the number of alveolar macrophages, interstitial cell infiltration, and chronic active inflammation), the nasal cavity (atrophy of olfactory epithelium), and the bronchial and mediastinal lymph nodes (lymphoid tissue hyperplasia) were observed (NTP TR453 (1996), ATSDR (2005), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). (3) It was reported that, in a 13-week inhalation exposure test with mice (6 hours/day, 5 days/week), at 0.3 to 1.2 mg/m3 (converted guidance value: 0.00022 to 0.00087 mg/L, within the range for Category 1), effects on the lung (increases in absolute and relative weight, an increase in the number of alveolar macrophages, interstitial lymphocytic infiltration, chronic active inflammation, fibrosis), the nasal cavity (atrophy of olfactory epithelium) and the bronchial lymph node (lymphoid tissue hyperplasia), and a slight increase in hemoglobin and red blood count (females) were observed (NTP TR453 (1996), ATSDR (2005), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). (4) It was reported that, in a 2-year inhalation exposure test with rats (6 hours/day, 5 days/week), at 0.15 to 1 mg/m3 (converted guidance value: 0.00015 to 0.0001 mg/L, within the range for Category 1), effects on the lung (fibrosis, chronic active inflammation, focal alveolar epithelial hyperplasia, macrophage proliferation, pulmonary alveolar proteinosis, interstitial pneumonia), the bronchial lymph node (lymphoid tissue hyperplasia, macrophage proliferation) and the nasal cavity (atrophy of olfactory epithelium/chronic active inflammation (only females)), and hematological effects (a slight increase in hematocrit and hemoglobin, an increase in red blood count (males)) were observed (NTP TR453 (1996), ATSDR (2005), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). (5) It was reported that, in a 2-year inhalation exposure test with mice (6 hours/day, 5 days/week), at 0.6 to 1.2 mg/m3 (converted guidance value: 0.0006 to 0.0012 mg/L, within the range for Category 1), effects on the lung (chronic active inflammation, bronchiolization (alveolar epithelial hyperplasia), macrophage proliferation, pulmonary alveolar proteinosis, interstitial cell infiltration, fibrosis), the nasal cavity (atrophy of olfactory epithelium, rhinitis), and the bronchial lymph node (lymphocyte proliferation and macrophage proliferation), and hematological effects in females (increases in hematocrit, segmented neutrophil, monocyte, lymphocyte, and total white cell count) were observed (NTP TR453 (1996), ATSDR (2005), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)).
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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