NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	10101-97-0
Chemical Name	Nickel sulfate hexahydrate
Substance ID	25A0072
Classification year (FY)	FY2013
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised	New
Classification result in other fiscal year
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance by the Japanese Government (July, 2013)
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	- -	-	-	Solid (GHS definition)
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Solid (GHS definition)
5	Gases under pressure	Not applicable	- -	-	-	Solid (GHS definition)
6	Flammable liquids	Not applicable	- -	-	-	Solid (GHS definition)
7	Flammable solid	Not classified	- -	-	-	It is estimated to be not combustible. (nickel sulfate anhydrate is not combustible (ICSC (2001)))
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 applicable	- -	-	-	Solid (GHS definition)
10	Pyrophoric solids	Not classified	- -	-	-	It is estimated to be not combustible. (nickel sulfate anhydrate is not combustible (ICSC (2001)))
11	Self-heating substances and mixtures	Not classified	- -	-	-	It is estimated to be not combustible. (nickel sulfate anhydrate is not combustible (ICSC (2001)))
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified	- -	-	-	From the information of being soluble in water (Merck (14th, 2006)), it is recognized that it does not react vigorously with water.
13	Oxidizing liquids	Not applicable	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	Classification not possible	- -	-	-	It is an inorganic compound which does not contain halogen but contains oxygen, however, the classification is not possible due to no data.
15	Organic peroxides	Not applicable	- -	-	-	It is an inorganic compound.
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid 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)	Category 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	There are reports on three oral LD50 values for rats of 300 mg/kg (ECETOC TR33 (1989)), 275 mg/kg (females), and 325 mg/kg (males) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). It was classified in Category 3 to which two of them corresponded. Besides, there are reports on LD50 values on nickel sulfate anhydrate (CAS RN 7786-81-4) for rats of 46 mg/kg (males), 39 mg/kg (females) (corresponding to Category 2) (ATSDR (2005)), 500 mg/kg (corresponding to Category 4) (ECETOC TR33 (1989)), 275 mg/kg (corresponding to Category 3) (ECETOC TR33 (1989)), and 325 mg/kg (corresponding to Category 4) (ECETOC TR33 (1989)).
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
2	Skin corrosion/irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, it is described in the Initial Risk Assessment Report (NITE, CERI, NEDO, 2008) that no skin irritation was observed in a test with rabbits. However, because it is unknown whether the test was according to the guideline, and there is no other information, it was classified as "Classification not possible."
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, it is described in the Initial Risk Assessment Report (NITE, CERI, NEDO, 2008) that no irritation was observed in one test. However, because it is unknown whether the test was according to the guideline, and there is no other information, it was classified as "Classification not possible."
4	Respiratory sensitization	Category 1	Danger	H334	P304+P340 P342+P311 P261 P284 P501	In the Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), there is a report on cases developing asthma for nickel sulfate, although the number is small. Nikel and inorganic nickel compounds are classified in occupational sensitizers to the airway Group 2 in the Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2013), "R42" in EU DSD classification, and "Resp. Sens. 1 H334" in EU CLP classification. From the above, it was classified in Category 1.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	Multiple results of maximization tests with guinea pigs, etc. are described in the Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), and all of them showed sensitization and gave positive results. Also, in epidemiological surveys or case reports in humans, multiple positive results are mentioned. Nickel and inorganic nickel compounds are classified in occupational skin sensitizers Group 1 in the Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2013), "R43" in EU DSD classification, and "Skin Sens. 1 H317" in EU CLP classification. From the above, it was classified in Category 1.
5	Germ cell mutagenicity	Classification not possible	- -	-	-	It 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. It is reported that nickel sulfate hexahydrate was negative in a micronucleus test with mouse bone marrow (Mutat. Res., 1997). In the literature, all of nickel sulfate hexahydrate, nickel chloride hexahydrate, and nickel oxide (III) were negative in micronucleus tests. As in vivo test data on nickel sulfate (unknown whether it is the anhydrate or hexahydrate), it was reported to be negative in a chromosomal aberration test with rat spermatogonial cells, micronucleus tests with bone marrow cells of rats and mice, and a chromosomal aberration test with rat bone marrow cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ATSDR (2005)). On the other hand, there are positive results in a micronucleus test with mice and DNA damage tests with mice and rats (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), but they were not assessed in ATSDR (2005). As for in vitro tests, data for that this substance could be specified are limited to a negative result in a bacterial reverse mutation test and a positive result in a gene mutation test with cultured mammalian cells (NTP DB (Access on August 2013)). Nickel sulfate (unknown whether it is the anhydrate or hexahydrate) was negative in a bacterial reverse mutation test and positive in a chromosomal aberration test and a gene mutation test with cultured mammalian cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ECETOC TR 33 (1989), ATSDR (2005)). From the above, from in vitro test data, it is judged to be positive, but because negative results are indicated in in-vivo tests, it was classified as "Classification not possible." Besides, nickel sulfate (CAS RN 7786-81-4) was classified as "Not classified."
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	Nickel sulfate, the anhydrate of this substance, are classified in Group 1 as nickel compounds by IARC (IARC (2012)), "Carc. Cat. 1; R45" in EU DSD classification, "Carc.1A H350i" in EU CLP classification, Group 2B by the Japan Society for Occupational Health (JSOH) (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health, 2013)), K by NTP (NTP (2002)), and A4 as soluble nickel compounds by ACGIH (ACGIH (1996)). Besides, it is described in NTP TR454 (1996) that there was no tumor increase in both 2-year inhalation tests with rats and mice. Among the above information, by giving priority to the year issued, the classification in IARC (2012) was adopted, and it was classified in Category 1A.
7	Reproductive toxicity	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, in a two-generation reproductive toxicity test and a three-generation reproductive toxicity test with rats in the oral route (gavage), no effects on reproductive and developmental toxicity were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). However, because no sufficient data on teratogenicity were obtained, it was classified as "Classification not possible" due to lack of data.
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, in the case of a two-and-a-half-year-old girl who accidentally ingested 5 g of nickel sulfate anhydrate, she had a cardiac arrest after 4 hours and died after 8 hours. Pathology examination revealed irritative changes in the gastrointestinal tract (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ECETOC TR 33 (1989)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs), Category 2 (liver, testis)	Danger Warning	H372 H373	P260 P264 P270 P314 P501	In 90-day administration tests (drinking water or gavage) with rats and a 2-year gavage administration test with rats, reduced weight gain, increased mortality, weight changes in a part of organs such as the kidney were observed at the doses (15-30 mg/kg/day) within the guidance value range for Category 2, but no organs showed histopathological changes (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). Furthermore, it is described that in 90-day or 2-year inhalation exposure test with rats or mice, inflammatory changes in the lung and bronchus, atrophy of the olfactory epithelium, etc. were found from the concentrations (converted guidance value: 0.0002 mg/L or below) within the range for Category 1 (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), NTP TR454 (1996), ACGIH (7th, 2001)), therefore it was classified in Category 1 (respiratory organs). Moreover, in a 30-day dermal exposure test with rats, other than changes in the skin at the application site, toxicity changes were observed in the liver (enlargement of hepatocytes, partial necrosis of the liver, swelling and congestion of the sinusoid) and testis (edema and degeneration in the seminiferous tubules) at the doses (converted guidance value: 20-30 mg/kg/day) corresponding to Category 2 (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). From the above, Category 1 (respiratory organs), Category 2 (liver, testis).
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)	Classification not possible	- -	-	-	No data available.
11	Hazardous to the aquatic environment (Long-term)	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.

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