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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	7664-39-3
Chemical Name	Hydrofluoric acid
Substance ID	R03-B-008-MHLW
Classification year (FY)	FY2021
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)
New/Revised	Revised
Classification result in other fiscal year	FY2017 FY2017 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)	- -	-	-	Hydrogen fluoride which is the target of classification is an anhydride and it was classified assuming that it was a practically gas (almost gasified). Besides, please refer to the classification of "Hydrofluoric acid (liquid)" having the same CAS RN. The boiling point information for hydrogen fluoride is 19.5 - 20 deg C, and there is no information to guarantees that it is completely gas at 20 deg C, and there is no certainty that it is a gas by GHS definition, but it is a practically gas.
2	Flammable gases	Not classified	- -	-	-	It was classified as "Not classified" from information that it is not combustible (ICSC (2017)).
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Classification not possible	- -	-	-	No data available.
5	Gases under pressure	Liquefied gas	Warning	H280	P410+P403	It was classified as a liquefied gas (low pressure liquefied gas) since a critical temperature of 188 deg C (GESTIS (Accessed Oct. 2021)) exceeds 65 deg C.
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Gas (GHS definition)
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Gas (GHS definition)
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	Gas (GHS definition)
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Gas (GHS definition)
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Gas (GHS definition)
11	Self-heating substances and mixtures	Not classified (Not applicable)	- -	-	-	Gas (GHS definition)
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified (Not applicable)	- -	-	-	Gas (GHS definition)
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Gas (GHS definition)
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Gas (GHS definition)
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Gas (GHS definition)
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to gas substances are not available.
17	Desensitized explosives	Not classified (Not applicable)	- -	-	-	Gas (GHS definition)

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] Gas (GHS definition). It was classified as "Not classified." Besides, please refer to the classification of hydrofluoric acid having the same CAS RN.
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Gas (GHS definition). It was classified as "Not classified."
1	Acute toxicity (Inhalation: Gases)	Category 1	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 1. Besides, based on new knowledge, the classification result was changed. [Evidence Data] (1) It was reported that the lethal concentration of anhydrous hydrofluoric acid fume was 50-250 ppm or higher at 5 minutes (clinical toxicology (2009)). [Reference Data, etc.] (2) LC50 for rats (1-hour): 966 ppm (converted 4-hour equivalent value: 483 ppm) (OEL Documentations (Japan Society for Occupational Health (JSOH), 2020), US AEGL (2004), EU RAR (2001), AICIS PEC (2001)) (3) LC50 for rats (1-hour): 1,000-2,300 ppm (converted 4-hour equivalent value: 500-1150 ppm) (DFG MAK (2001)) (4) LC50 for rats (1-hour): 2,229-2,328 ppm (converted 4-hour equivalent value: 1114.5-1164 ppm) (GLP) (EU RAR (2001)) (5) LC50 for rats (1-hour): 1,276 ppm (converted 4-hour equivalent value: 638 ppm) (US AEGL (2004)) (6) LC50 for rats (1-hour): 1,304 ppm (converted 4-hour equivalent value: 652 ppm) (EU RAR (2001))
1	Acute toxicity (Inhalation: Vapours)	Not classified	- -	-	-	[Rationale for the Classification] Gas (GHS definition). It was classified as "Not classified."
1	Acute toxicity (Inhalation: Dusts and mists)	Category 1	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 1. Besides, as for the data in (1), the values converted to mist were used for classification. Based on the new findings, the classification result was changed. [Evidence Data] (1) It was reported that the lethal concentration of anhydrous hydrofluoric acid fume was 50 to 250 ppm (mist, converted 4-hour equivalent value: 0.0008 to 0.004 mg/L) or higher (Clinical Toxicology (2009)).
2	Skin corrosion/irritation	Category 1	Danger	H314	P301+P330+P331 P303+P361+P353 P305+P351+P338 P304+P340 P260 P264 P280 P310 P321 P363 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1. [Evidence Data] (1) Hydrogen fluoride and hydrofluoric acid (liquid) were corrosive or highly irritating to skin and mucosa membranes (DFG MAK (2001)). (2) Clinical symptoms (pain, swelling, blister, erythema and necrosis) caused by dermal exposure to hydrogen fluoride appeared after several hours in many cases (OEL Documentations (Japan Society For Occupational Health (JSOH), 2020)). (3) Skin contact with pure hydrogen fluoride caused second and third degree burns to 3.6% of the body surface and systemic effects (nausea, vomiting, bradycardia, polyuria) (OEL Documentations (Japan Society For Occupational Health (JSOH), 2020), AICIS (previous NICNAS) PEC (2001)). (4) In the Ministry of Labour Notification No. 33 issued in 1996 (revised by the Ministry of Health, Labour and Welfare Notification No. 316 in 2013), this substance is designated as "Hydrofluoric acid (including hydrogen fluoride)" in simple chemical substances or compounds (including alloys) designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act, and diseases (skin disorders, disorders in the anterior part of the eye, respiratory tract and lung disorders) with specific symptoms or disorders caused by occupations exposed to this substance as main symptoms or disorders are designated as occupational diseases.
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1. [Evidence Data] (1) It was classified in Category 1 for skin corrosion/irritation. (2) Two male volunteers were exposed to hydrogen fluoride at the concentrations of 0.026, 0.05, and 0.1 mg/l (32, 61, and 122 ppm) for a very short time. Inhalation at 122 ppm produced marked irritation to the conjunctiva and respiratory organs within one minute and caused dermatopathy. At 61 ppm, marked irritation to the eyes and nose was observed but no dermatopathy was observed. At 32 ppm, irritation to the eye and nose was mild and tolerable with discomfort. At all concentrations, irritation to the respiratory tract and sour taste in the mouth were observed (OEL Documentations (Japan Society For Occupational Health (JSOH), 2020)). (3) In the Ministry of Labour Notification No. 33 issued in 1996 (revised by the Ministry of Health, Labour and Welfare Notification No. 316 in 2013), this substance is designated as "Hydrofluoric acid (including hydrogen fluoride)" in simple chemical substances or compounds (including alloys) designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act, and diseases (skin disorders, disorders in the anterior part of the eye, respiratory tract and lung disorders) with specific symptoms or disorders caused by occupations exposed to this substance as main symptoms or disorders are designated as occupational diseases.
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Reference Data, etc.] (1) As for in vivo, it was reported that, in a chromosomal aberration test using the rat bone marrow cells (inhalation exposure, 1 mg/m3, one month (6 hours/day, 5 days/week)), positive results (hyperploidy) were obtained, and in a dominant lethal test with mice, negative results were obtained (ACGIH (2005), OEL Documentations (Japan Society For Occupational Health (JSOH), 2020), EU RAR (2001), REACH registration dossier (Accessed Oct. 2021)). (2) As for in vitro, it was reported that, in a bacterial reverse mutation assay, negative results were obtained (OEL Documentations (Japan Society For Occupational Health (JSOH), 2020), EU RAR (2001), REACH registration dossier (Accessed Oct. 2021)). (3) No conclusion could be drawn from the results of the in vivo tests in (1) (the chromosomal aberration test with the rat bone marrow cells, the dominant lethal test with mice). The positive results (hyperploidy) in the chromosomal aberration test were observed in abnormality in anaphase cells. However, since fluorine ion does not bind to DNA covalently and no DNA-adducts are formed, it was considered to be a secondary effect and the EU concluded that inorganic fluoride did not induce chromosomal damage in vivo (EU RAR (2001)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory organs, cardiovascular system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1) to (7), since there were respiratory organs and cardiovascular system effects in the findings in human and animals, it was classified in Category 1 (respiratory organs, cardiovascular system). [Evidence Data] (1) It was reported that splashes of this substance on the face resulted in fatal pulmonary edema and systemic effects including hypocalcemia and hypomagnesemia (OEL Documentations (Japan Society For Occupational Health (JSOH), 2020)). (2) It was reported that 23 male volunteers who were healthy and nonsmokers were exposed to this substance at low levels (0.2 to 0.6 mg/m3), intermediate levels (0.7 to 2.4 mg/m3), and high levels (2.5 to 5.2 mg/m3) for one hour (initially at rest for 45 minutes, 75W bicycle ergometer exercise for the remaining 15 minutes) and the upper respiratory tract and lower respiratory tract irritation symptoms were assessed in 6 stages from 0 (none) to 5 (very strong). The results were reported that the difference in the scores for upper respiratory tract symptoms between before and after the exposure in the high-level group was significantly higher than that in the low- and intermedium-level groups and almost all symptoms disappeared 4 hours after the exposure (OEL Documentations (Japan Society For Occupational Health (JSOH), 2020)). (3) It was reported that, in a study of intranasal reaction by nasal lavage (NAL) after a one-hour exposure at 3.3 to 3.9 mg/m3 in humans, subjective symptoms, which were exacerbated upper respiratory tract symptoms, were observed in 7 of 10 subjects and an increase in neutrophils, an increase in arachidonate metabolites (PGE2, LTB4), an increase in TNF- alpha, and an increase in protein were observed (OEL Documentations (Japan Society For Occupational Health (JSOH), 2020)). (4) It was reported that, in a study with volunteers exposed by inhalation at 2.5 mg/m3 for one hour or more, increased airway symptoms (itching and soreness) were observed, and in a separate study, irritation of the eyes, skin and nasal mucosa were found at average concentration as low as 1.16 mg/m3. In a study in human volunteers using bronchoalveolar lavage after one-hour hydrogen fluoride inhalation, there were indications of inflammation at the intermediate (0.7 to 2.4 mg/m3) and high (2.5 to 5.2 mg/m3) levels tested, but not the lowest level (<=0.6 mg/m3) (AICIS PEC (2001)). (5) It was reported that exposure to very high levels of hydrogen fluoride/hydrofluoric acid could result in severe cardiovascular effects, which were attributed to a combination of hypocalcemia and hyperkalemia, and there were cases of cardiac arrythmia in humans exposed to hydrofluoric acid splashes on the face (ATSDR (2003)). (6) It was reported that, in an acute inhalation exposure test with monkeys (for 1 hour), difficulty in breathing, paralysis, lacrimation, nasal discharge, nausea, sneezing, and vomiting were observed at 690 ppm (converted 4-hour equivalent value: 345 ppm, within the range for Category 1). Besides, it was reported that the LC50 was 1,774 ppm and prominent pulmonary hemorrhage and edema were observed at necropsy (OEL Documentations (Japan Society For Occupational Health (JSOH), 2020)). (7) It was reported that, in an acute inhalation exposure test with rabbits, myocardial necrosis and congestion were observed at 23 ppm (within the range for Category 1) (ACGIH (2005), ATSDR (2003)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (teeth, respiratory organs, bone, nervous system)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1), effects on bones and tooth were considered in the human findings, and based on (2) to (4), effects on teeth, respiratory organs, bones, and nervous system were considered in the findings in animals, and it was classified in Category 1 (teeth, respiratory organs, bone, nervous system). [Evidence Data] (1) It was reported that, in humans, fluorine accumulated in bones and tooth germs and chronic exposure to high levels of fluoride and hydrogen fluoride resulted in skeletal fluorosis (OEL Documentations (Japan Society For Occupational Health (JSOH), 2020)). (2) It was reported that, in one-month repeated inhalation exposure test with rats (6 hours/day), damage to the dental enamel, atrophy and local edema of the bronchial mucosa (young animals), peribronchial hyperplasia in the lungs (older animals), and formation of irregular shaped cavities in bones in animals aged 12 months were observed at 1.2 ppm (converted guidance value: 0.286 ppm, within the range for Category 1) (REACH registration dossier (Accessed Oct. 2021)). (3) It was reported that, in a 91-day repeated inhalation exposure test with rats (GLP, 6 hours/day, 5 days/week), clinical signs such as a marked decrease in body weight, red ocular discharge, and rough coats, and dental malocclusions were observed at 10 ppm (7.14 ppm, within the range for Category 1) (REACH registration dossier (Accessed Oct. 2021)). (4) It was reported that, in a 5-month repeated inhalation exposure test with rats, diminished conditioned responses and increased time before motor nerve response were observed at 0.03 ppm (within the range for Category 1), and histological changes in the nerve cell synapses were observed at 0.1 ppm (within the range for Category 1) (ATSDR (2003)). [Reference Data, etc.] (5) It was reported that some evidence of early skeletal fluorosis was observed in workers exposed to hydrogen fluoride and fluoride dusts. These studies did not adequately characterize the relationship with fluoride exposure levels and, in most of the studies, there was some uncertainty regarding the diagnosis of skeletal fibrosis (ATSDR (2003)).
10	Aspiration hazard	Not classified	- -	-	-	[Rationale for the Classification] Gas (GHS definition). It was classified as "Not classified."

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)	-	- -	-	-	-
11	Hazardous to the aquatic environment Long term (Chronic)	-	- -	-	-	-
12	Hazardous to the ozone layer	-	- -	-	-	-

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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