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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	7681-49-4
Chemical Name	Sodium fluoride
Substance ID	H29-B-005
Classification year (FY)	FY2017
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 (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	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 solids	Not classified	- -	-	-	It is not combustible (ICSC (J) (2003)).
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 not combustible (ICSC (J) (2003)).
11	Self-heating substances and mixtures	Not classified	- -	-	-	It is not combustible (ICSC (J) (2003)).
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified	- -	-	-	It contains metals (Na), but it is estimated that it does not react vigorously with water from the observation result of water solubility of 4.0 g/100 mL (20 deg C) (ICSC (J) (2003)).
13	Oxidizing liquids	Not applicable	- -	-	-	Solid (GHS definition).
14	Oxidizing solids	Classification not possible	- -	-	-	It is an inorganic compound containing fluorine, 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 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	Eight LD50 values for rats of 31 mg fluoride (F)/kg, 52 mg F/kg, 54 mg F/kg, 85.5 mg F/kg, 101.3 mg F/kg, 126.3 mg F/kg (ATSDR (2003)), 32 mg F/kg, and 51.6 mg F/kg (IARC 27 (1982)) were reported. When the LD50 values are converted to the amount of sodium fluoride using the NaF molecular weight of 41.99 and F-atom molecular weight of 19.00, these values correspond to 69 mg/kg, 110 mg/kg, 120 mg/kg, 189 mg/kg, 223.9 mg/kg, 279.1 mg/kg, 71 mg/kg and 114 mg/kg, respectively, and all of these values correspond to Category 3. Therefore, this substance was classified in Category 3.
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	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	There is a report that in a primary dermal irritation test (EPA OPPTS 870.2500) with rabbits, slight irritation was observed (EPA Pesticide (2007)). There is a report that in a dermal irritation test with rats applied for 24 hours, superficial necrosis, edema and inflammation were observed (ATSDR (2003)). Therefore, this substance was classified in Category 2. Besides, this substance is classified as "Skin. Irrit. 2 H315" in EU CLP classification (ECHA CL Inventory (Access on May 2017)). Along with the revision of the GHS Classification Guidance for the Japanese Government, the category was revised.
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	There are reports that in eye irritation tests with rabbits, corneal epithelial defects and necrosis in the conjunctiva (EHC 227 (2002)), or severe irritation (EPA Pesticide (2007)) were observed. Therefore, this substance was classified in Category 1. Besides, this substance is classified as "Eye. Irrit. 2 H319" in EU CLP classification (ECHA CL Inventory (Access on May 2017)).
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, in EPA Pesticide (2007) there is a report that it was negative in the Buehler test. However, this was not adopted because the details were unknown.
5	Germ cell mutagenicity	Classification not possible	- -	-	-	As for in vivo, positive and negative results in micronucleus tests with mice, negative in a micronucleus test with rats, positive and negative results in chromosome aberration tests with mice, negative in sister chromatid exchange tests with mice and hamsters, and negative in a DNA break test with rat testis cells were reported (ATSDR (2003), DFGOT (2015) (Access on May 2017), EHC 227 (2002)). As for in vitro, negative in a bacterial reverse mutation test, positive and negative results in a mammalian cell gene mutation test and in a mouse lymphoma assay, and positive and negative in a chromosome aberration test and in a sister chromatid exchange test were reported (ATSDR (2003), DFGOT (2006) (Access on May 2017), EHC 227 (2002), NTP TR393 (1990)). However, it is described in DFGOT (2006) (Access on May 2017) that this substance increased the dose-dependent chromosomal aberrations at 10 microg/mL or more in vitro, which was not observed in an appropriate in vivo test. In addition, it is described that there is no evidence of germ cell mutagenicity. From the above, although positive results were observed, they are not appropriate results, therefore, this substance was classified as "Classification not possible" according to the GHS Classification Guidance for the Japanese Government.
6	Carcinogenicity	Classification not possible	- -	-	-	In NTP carcinogenicity tests with rats and mice dosed by drinking water for two years, a slight increase in the incidence of osteosarcoma in male rats was observed. This was regarded as equivocal evidence of carcinogenicity, but it was concluded that there is no evidence of carcinogenicity in female rats and male and female mice (NTP TR393 (1990), EU-RAR (2001)). Moreover, in carcinogenicity tests with rats and mice dosed by feeding for two years, it was negative in rats. On the other hand, in mice, an increase in osteoma was observed at the high dose, however, there was the retroviral infection, so, it is regarded that the increase in osteoma is not conclusive (EU-RAR (2001)). In classification results by other organizations, this substance is classified in D by EPA (EPA Pesticides (2007)), fluorides are classified in A4 by ACGIH (ACGIH (7th, 2001)), and fluorides (inorganic, used in drinking water) are classified in Group 3 by IARC (IARC Suppl. 7 (1987)), respectively. From the above, it was classified as "Classification not possible" based on the test results and the classification results by other organizations.
7	Reproductive toxicity	Classification not possible	- -	-	-	Both in two-generation studies with rats dosed by drinking water and developmental toxicity studies with rats or rabbits, there were no effects or only minor effects, which were not adopted as evidence for classification at doses where maternal toxicity was manifested (EU-RAR (2001), DFGOT (2015) (Access on May 2017), ATSDR (2003)). From the above, this substance does not have apparent reproductive and developmental toxicity on the oral route and could not be classified due to lack of data.
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system, heart, kidney)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	In humans, it was reported that ingestion of this substance by accidental ingestion or suicide attempt caused nausea, vomiting, abdominal colics and diarrhea, and that in some cases, clonic convulsion and pulmonary edema probably due to aspiration of vomitus were observed (ATSDR (2003)). There is a report that a 3-year-old boy who accidentally ingested 200 tablets of this substance (16 mg F/kg, a converted value equivalent to sodium fluoride: 35.36 mg/kg) died after 7 hours. Upon autopsy, hemorrhagic edema of the lungs, hemorrhagic gastritis, and cerebral edema were observed (ATSDR (2003)). In addition, there is a report that a man who orally ingested 120 g of insecticide powder containing 97% of this substance in a suicide attempt exhibited muscle tetany, ventricular fibrillation and esophageal stricture after 2 hours (ATSDR (2003)). There is a description that fluoride ions bind with serum calcium resulting in hypocalcemia, which may cause muscle tetany, decreased myocardial contractility, and cardiovascular collapse (ATSDR (2003)). As for experimental animals, the lethal dose due to an oral dose of a fluoride including this substance is in the range of 20-100 mg F/kg. Also, acute intoxication symptoms, salivation, lacrimation, vomiting, diarrhea, muscular fibrillation, and respiratory, cardiac, and general depression are reported (EHC 36 (1984)). In addition, it was reported that a single oral administration of 50 mg/kg of this substance in rats caused polyuria and increased urinary excretion of inorganic phosphorus, calcium, magnesium, potassium, and sodium (EHC 36 (1984)). These doses are equivalent to Category 1. By examining the above information comprehensively, the target organs for this substance are considered to be the nervous system, heart and kidneys. In addition, in the previous classification, the liver was also adopted as the target organ based on the evidence that cloudy swelling was noted in the liver upon autopsy in the death case of the child due to accidental ingestion described in ATSDR (2003). However, because there is no result other than this one case report and details are unknown, it was not adopted as evidence for classification. From the above, this substance was classified in Category 1 (nervous system, heart, kidney).
9	Specific target organ toxicity - Repeated exposure	Category 1 (teeth, bone), Category 2 (heart, liver, kidney, genetic organs (men))	Danger Warning	H372 H373	P260 P264 P270 P314 P501	As for humans, there is no information on this substance. However, there is a report of lesions in bones related to fluorosis due to occupational exposure to inorganic fluoride in ACGIH's "FLUORIDES" (ACGIH (7th, 2001)). As for experimental animals, there are reports as follows: in 26-week repeated oral dose toxicity tests with rats and mice given in drinking water, in the rats, hyperplasia of the gastric mucosa at 100 ppm (converted guidance value: 12.5 mg/kg/day), which is within the guidance value range for Category 2, and depressed body weight gains, focal degeneration of the enamel of incisor teeth, and gastric ulceration were observed at 300 ppm (converted guidance value: 37.5 mg/kg/day). In the mice, increased osteoid at or above 50 ppm (converted guidance value: 10 mg/kg/day) that is within the guidance value range of Category 1, focal degeneration of the enamel of incisor teeth at 300 ppm (converted guidance value: 60 mg/kg/day) that is within the guidance value range of Category 2, and in the early death case of the same group, acute nephrosis, liver lesions (multinucleated giant cells), myocardial lesions (degeneration, accumulations of mineral), and testis lesions (necrosis, degeneration of the seminiferous tubules, multinucleated giant cells in the seminiferous tubules) were observed; In 103-week repeated oral dose toxicity tests with rats and mice given by drinking water, in the rats, dentine dysplasia of incisor teeth, degeneration of odontoblast, degeneration of ameloblasts at or above 25 ppm (converted guidance value: 3.1 mg/kg/day) that is within the guidance value range of Category 1, and osteosclerosis at 175 ppm (converted guidance value: 21.9 mg/kg/day), which is within a guidance value range of Category 2 were observed. In the mice, gross abnormalities (attrition, discoloration, mottling) and dentine dysplasia at 175 ppm (converted guidance value: 35 mg/kg/day), which is within the guidance value range of Category 2 were observed (NTP TR393 (1990)); In a 14-day inhalation toxicity test (4 hours/day) with mice, pulmonary edema is reported at 10 mg/m3 (converted guidance value: 0.001 mg/L), which corresponds to Category 1 (ATSDR (2003)). This inhalation data was not used for classification because the exposure period was short and the information is not sufficient. Of the above, gastric changes were not adopted as evidence of classification because of a finding based on irritation. Therefore, this substance was classified in Category 1 (teeth, bone) and Category 2 (heart, liver, kidneys, genetic organs (men)). Besides, for fluorides, bone lesions due to fluorosis were added. Since lethargy, which is evidence for the nervous system in the previous classification, was only symptomatic and only observed along with dehydration in a 14-day dose test, it was not adopted as evidence of the classification. Also, pulmonary edema was not adopted as evidence of classification for the above reasons. Other than these, the contents were reconfirmed. From the above, the classification result was changed.
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)	Category 3	- -	H402	P273 P501	From 96-hour EC50 (immobile) = 84.6 mg/L [converted value 38.28 mgF/L] for crustacea (Chaetogammarus marinus) (ECETOC TR91: 2003), it was classified in Category 3.
11	Hazardous to the aquatic environment (Long-term)	Not classified	- -	-	-	The target substance is an inorganic compound, and its behavior in water is unknown. However, due to water solubility of 43,000 mg/l, 21-day NOEC (reproduction) = 8.2 mg/L [converted value 3.7 mgF/L] for crustacea (Daphnia magna) (NICNAS PEC: 2001, EU RAR: 2001), 72-hour NOEC (rate method) => 464 mg/L [converted value 210 mgF/L] for algae (Pseudokirchneriella subcapitata) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2017)), and 28-day NOEC (early life stage test) => 9.9 mg/L [NaF] for fish (Oryzias latipes) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2017)), 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.
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* 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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