GHS Classification Result

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GENERAL INFORMATION
Item Information
CAS RN 10141-05-6
Chemical Name Cobalt(II) bis(nitrate)
Substance ID H28-A-053, C-112A
Classification year (FY) FY2016
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 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 Classification not possible
-
-
- -  There is a chemical group associated with explosive properties (nitrates) present in the molecule, but the classification is not possible due to no data.
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 solids Not classified
-
-
- -  It is not combustible (ICSC (J) (2013)).
8 Self-reactive substances and mixtures Classification not possible
-
-
- -  There is a chemical group associated with explosive properties (nitrates) present in the molecule, but the classification is not possible due to no data.
9 Pyrophoric liquids Not applicable
-
-
- -  Solid (GHS definition).
10 Pyrophoric solids Not classified
-
-
- -  It is not combustible (ICSC (J) (2013)).
11 Self-heating substances and mixtures Not classified
-
-
- -  It is not combustible (ICSC (J) (2013)).
12 Substances and mixtures which, in contact with water, emit flammable gases Not classified
-
-
- -  It contains a metal (Co), but it is estimated that it does not react vigorously with water because the measured water solubility data of 103 g/100 g was obtained (R.Lide (2010)).
13 Oxidizing liquids Not applicable
-
-
- -  Solid (GHS definition).
14 Oxidizing solids Classification not possible
-
-
- -  It is estimated to be oxidizing due to a nitrate, but 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 4


Warning
H302 P301+P312
P264
P270
P330
P501
 This substance was classified in Category 4, based on a report of an LD50 value (OECD TG 401) of 434 mg/kg (SIAP (2014), HSDB (Access on July 2016)) for rats.
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 Not classified
-
-
- -  It is described that, in a skin irritation test (OECD TG 404) in rabbits, because the values of erythema and oedema were below the threshold irritation score of ? 2.3 and the effects were fully recovered within 48 hours, the substance was not irritating (SIAP (2014)). Therefore, this substance was classified as "Not classified."
3 Serious eye damage/eye irritation Category 1


Danger
H318 P305+P351+P338
P280
P310
 It is described in SIAP that "The soluble cobalt salts present a hazard for human health, based on the bioaccessibility of cobalt ions (acute oral toxicity, respiratory and eye irritation, skin sensitization, repeated dose toxicity, carcinogenicity and reproduction)." (SIAP (2014)). Also it is reported that irreversible effects were observed in an eye irritation test (OECD TG 405) in rabbits. Therefore, this substance was classified in Category 1.
4 Respiratory sensitization Category 1A


Danger
H334 P304+P340
P342+P311
P261
P284
P501
 According to the Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2015), cobalt and its compounds are listed in Group 1 of occupational sensitizers to the airways. Also, it is shown that IgA and IgE antibodies against cobalt were generated in workers who had engaged in metalworking for a long time and had developed symptoms of asthma, and cobalt functions as a hapten (ATSDR (2004)). From the above, this substance was classified in Category 1. In addition, this substance is classified in "Resp. Sense 1 H334" in the EU CLP Classification (ECHA C&L Inventory (Access on September 2016)).
4 Skin sensitization Category 1A


Warning
H317 P302+P352
P333+P313
P362+P364
P261
P272
P280
P321
P501
 According to the Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2015), cobalt and its compounds are listed in Group 1 of occupational sensitizers to the skin. Also, there are many reports that cobalt causes dermatitis in humans, and that cobalt chloride and cobalt sulfate are skin sensitizers in experimental animals (ATSDR (2004)) and it was suggested that this substance had skin sensitization similar to cobalt chloride and cobalt sulfate (SIAP (2014)). Therefore, this substance was classified in Category 1A. In addition, this substance is classified as "Skin Sense 1 H317" in the EU CLP Classification (ECHA C&L Inventory (Access on September 2016)).
5 Germ cell mutagenicity Classification not possible
-
-
- -  There are no data available for this substance itself. However, as for in vivo tests, it was reported that the results were positive in micronucleus tests and chromosomal aberration tests using mouse bone marrow cells for cobalt dichloride, a soluble cobalt(II) compound (ATSDR (2004), CICAD 69 (2009), The Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)), but these data are not fully reliable or valid. It is reported that significant increases in micronuclei or DNA damage in peripheral blood were not detected in exposure to workers (SIAP (2014)).
 As for in vitro tests, both positive and negative results were reported for bacterial reverse mutation tests. A micronucleus test, a chromosomal aberration test, and a gene mutation test in cultured mammalian cells were positive (ATSDR (2004), CICAD 69 (2009), The Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), IARC 52 (1991)), but in in vitro micronucleus tests performed using mouse bone marrow cells isolated from the in vivo micronucleus tests described above, the result was negative regardless of the presence or absence of "S9." In SIAP (2014), it was described that soluble cobalt does not show mutagenicity (mutations) to bacteria and cells, but does show chromosomal damage in vitro, and that this is presumed to be due to reactive oxygen species (ROS). According to the weight of evidence, based on negative findings in in vivo chromosomal damage tests and negative findings in human occupational exposure, it was said that protective processes are effective in vivo. From the above, because it was assumed that soluble cobalt compounds have no in vivo effect, this substance was classified as "Classification not possible."
6 Carcinogenicity Category 2


Warning
H351 P308+P313
P201
P202
P280
P405
P501
 There are no test results for this substance itself. As for cobalt sulfate and other soluble divalent cobalt salts, IARC classified them in Group 2B (IARC 52 (1991)). As for cobalt and cobalt salts, NTP classified them in R (NTP RoC (14th, 2016)), the Japan Society For Occupational Health (JSOH) classified them in Group 2B (Recommendation of Occupational Exposure Limits (2016)). Therefore, this substance was classified in Category 2. Moreover, EU classified this substance in Carc. 1B and designated this substance as SVHC (ECHA (2011)).
7 Reproductive toxicity Category 1B


Danger
H360 P308+P313
P201
P202
P280
P405
P501
 There is information that this substance is soluble in water (CICAD 69 (2006)).
 Although there is no information on the reproductive effects of this substance itself, it is considered that the information on soluble cobalt compounds was considered available for the classification. In a test in which cobalt chloride hexahydrate was fed to male rats (265 ppm: 20 mg Co/kg/day), moderate to severe congestion appeared in the testes after administration for 35 days; and significant effects on spermatogonial cells, spermatocytes and sperm cells were observed in addition to degenerative or necrotic changes in the germinal epithelium of the testes and Sertoli cells after administration for 70 days (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)). In a test where male mice administered cobalt(II) chloride in drinking water for 12 weeks were mated with unexposed females, decreases were observed in the epididymal sperm count and in the survival of newborn pups at doses of 200 mg/L or higher. At doses of 400 mg/L or higher, the number of pregnant animals was reduced (declining fertility of males), testis weights decreased, and testicular sperm counts and daily sperm production decreased. Also in a tissue observation of the testes, hypertrophy of the interstitial Leydig cells, congested blood vessels, degeneration of the spermatogonial cells, and necrosis of seminiferous tubules and interstitial tissue were observed at doses of 400 mg/L or higher (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), CICAD 69 (2006)). In another study in which pregnant rats were given cobalt sulfate by gavage (gestation day 1 to 21), from the 50 mg/kg/day dose level, which is lower than the level of maternal toxicity expression at 100 mg/kg/day, relative weight decrease of liver, adrenal gland, or spleen were observed), fetuses were reported to have malformations (malformations of the cranium, spinal column, renal pelvis, renal tubule, ovary, and testis). It was also reported that in orally administered pregnant mice (gestation days 6 to 15), at 50 mg/kg/day, malformations of eyelids, kidneys, cranium, and spine occurred in fetuses (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)).
 From the above, for soluble cobalt compounds, harmful effects on male genetic organs and consequent reduction in fertility by the oral route, and teratogenicity observed at dose levels without the maternal toxicity were reported. This substance is also a soluble cobalt compound, and it is considered that similar reproductive and developmental toxicities are likely to occur. Therefore, this substance was classified in Category 1B. Moreover, EU had classified this substance in Repr. 1B along with other soluble cobalt compounds such as cobalt sulfate and cobalt dichloride, and designated this substance as SVHC (ECHA (2011)).
8 Specific target organ toxicity - Single exposure Category 2 (central nervous system, gastrointestinal tract), Category 3 (respiratory tract irritation)



Warning
H371
H335
P308+P311
P260
P264
P270
P405
P501
P304+P340
P403+P233
P261
P271
P312
 There is information that this substance is soluble in water (CICAD 69 (2006)).
 This substance and other soluble cobalt salts, cobalt (II) chloride (CAS RN 7646-79-9), cobalt (II) sulfate (CAS RN 10124-43-3), and cobalt (II) acetate (CAS RN 71-48-7) caused sedation, diarrhoea, tremors and convulsions prior to death, decrease in body temperature, increased heart rate, and piloerection at the highest dose (equivalent amount to Category 2) in acute oral toxicity tests in rats. However, no macroscopic alterations were observed in the most significant organs, and most effects disappeared after 72 hours (SIAP (2014)).
 Furthermore, it is also described that cobalt compounds caused hypothermia in rats by single oral administration (ATSDR (2004)), however, it is reported in the original literature (Speijers et al., Food Chem Toxicol. 20: 311 (1982)) that in the single oral dose test using rats with cobalt nitrate hexahydrate (CAS RN 10026-22-9), a hexahydrate of this substance, dose-related hypothermia, and at highest doses of 2,250 mg/kg (equivalent anhydrate amount: 1,413 mg/kg) sedation and diarrhea, were observed (ATSDR (2004)). Also, in a single oral dose test using rats of cobalt (II) dichloride, depression of spontaneous activity, muscle tone, and respiration and effects on the gastrointestinal tract were reported at doses equivalent to Category 1 (ATSDR (2004)). Therefore, it was classified in Category 1 (central nervous system, gastrointestinal tract) in the GHS Classification (FY 2015). Taking the above information together, this substance, as with other soluble cobalt salts, may also have effects on the central nervous system and the gastrointestinal tract. Since the symptoms described in SIAP and ATSDR were seen at doses equivalent to Category 2, this substance was classified in Category 2 (Central nervous system, gastrointestinal tract).
 Furthermore, there is a description that the dust of this substance irritates the nose and throat, and inhalation of this substance causes coughs and dyspnea in humans (HSDB (Access on September 2016)). Therefore, this substance was classified in Category 2 (central nervous system, gastrointestinal tract), and Category 3 (respiratory tract irritation).
9 Specific target organ toxicity - Repeated exposure Category 1 (nervous system, respiratory organs, cardiovascular system, thyroid, haemal system), Category 2 (genetic organs (men))


Danger
Warning
H372
H373
P260
P264
P270
P314
P501
 There is information that this substance is soluble in water (CICAD 69 (2006)).
 No data on this substance with regard to humans or experimental animals is available.
 As information for soluble cobalt compounds, in humans, the following was reported as overdose symptoms from cobalt chloride or cobalt sulfate administered for the treatment of anemia: effects on the nervous system (anorexia, nausea, tinnitus, hearing loss, neuropathy) and the thyroid (goiter and inhibition of thyroid iodine uptake). As a result of oral administration of cobalt chloride to volunteers, it was reported that erythroid haematopoiesis was enhanced and there were many complaints of headaches and abdominal discomfort as subjective symptoms (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), CICAD 69 (2006)). Also, as cobalt sulfate had been added for the purpose of stabilizing the foam on beer, deaths due to cardiomyopathy were reported among heavy beer drinkers and myocardial damage action of cobalt was a concern (CICAD 69 (2006), ACGIH (7th, 2001)). By restricting the addition of cobalt, it is said that the occurrence of cardiomyopathy and resulting death disappeared (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)). From the above, the nervous system, cardiovascular system, thyroid, and haemal system could be cited as target organs for repeated exposures of soluble cobalt compounds, including this substance, in humans.
 As for experimental animals, in tests using rats dosed with cobalt dichloride by gavage for 7 months, increases in red blood cell numbers and hemoglobin levels were observed at doses of 0.5 mg Co/kg/day or more (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), ATSDR (2004)). Blood effects were also observed in tests in which cobalt chloride hexahydrate was orally administered to rats for 8 weeks (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), ATSDR (2004)). In addition, in inhalation exposure tests of cobalt sulfate heptahydrate using rats or mice for 13 weeks or 2 years, inflammatory tissue changes were observed in the respiratory organs in both rats and mice from the low concentration of 0.3 mg/m3 (0.11 mg/m3 as cobalt). Additionally, in the 13-week exposure test using rats, an influence in the blood (polycythemia, platelet count reduction, increased reticulocyte counts) was observed (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), CICAD 69 (2006)). Furthermore, it was reported that in a test in which cobalt dichloride was administered in the drinking water for 12 weeks at concentrations of 200 to 800 ppm to male mice, a decrease in the weight of the testes, a decrease in the epididymal sperm count, reduced daily sperm production and necrosis of seminiferous tubules and interstitial tissue were observed at doses of 400 to 800 ppm (47 to 93 mg/kg/day, 21 to 42 mg/kg/day as cobalt) (converted guidance value: 19.6 to 39.2 mg/kg/day) (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), CICAD 69 (2006)). From the above, it was considered that the target organs of soluble cobalt compounds are the respiratory organs, haemal system, testes; and the effects on testes and that on others correspond to Category 2 and category 1, respectively.
 Therefore, based on the information regarding the effects of repeated exposure to soluble cobalt compounds on humans and experimental animals, this substance was classified in Category 1 (nervous system, respiratory organs, cardiovascular system, thyroid, haemal system) and Category 2 (genetic organs (men)).
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) Not classified
-
-
- -  From 48-hour LC50 = 172 mg/L for crustacea (Artemia salina) (CICAD 69, 2006), it was classified as "Not classified."
11 Hazardous to the aquatic environment (Long-term) Not classified
-
-
- -  Reliable chronic toxicity data were not obtained. Because it is poorly water soluble (water solubility = 103 g/100 g water, R.Lide, 2010), and classified as "Not classified" for acute toxicity, it was classified as "Not classified."
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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