NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	108-24-7
Chemical Name	Acetic anhydride
Substance ID	R01-B-021
Classification year (FY)	FY2019
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	FY2018 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)
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	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2	Flammable gases	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	Category 3	Warning	H226	P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501	It was classified in Category 3 based on a flash point of 49 deg C (closed cup) (Hommel (1991)).
7	Flammable solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
8	Self-reactive substances and mixtures	*	- -	-	-	There are no chemical groups associated with explosive or self-reactive properties present in the molecule. It was classified as "Not classified (Not applicable)."
9	Pyrophoric liquids	*	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from an autoignition temperature of 330 deg C (Hommel (1991)).
10	Pyrophoric solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
11	Self-heating substances and mixtures	*	- -	-	-	Classification is not possible because test methods applicable to liquid substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). It was classified as "Not classified (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	Category 1	Warning	H290	P234 P390 P406	It was classified in Category 1 from the information that it attacks many metals (ICSC (2006)), and it binds to moisture to attack iron and steel heavily (Hommel (1991)). Besides, it is classified in Class 8, Subsidiary Risk 3, PG II in UNRTDG (UN 1715).
17	Desensitized explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

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	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 4. [Evidence Data] (1) LD50 for rats: 630 mg/kg (DFGOT vol.13 (1999)) (2) LD50 for rats: 1,780 mg/kg (ACGIH (7th, 2001), ACGIH (7th, 2011), DFGOT vol.13 (1999), SIDS (2002), BUA 70 (1991), HSDB (Access on June 2019)) (3) LD50 for rats: 1,800 mg/kg (SIDS (2002))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: 4,000-4,320 mg/kg (ACGIH (7th, 2011)) (2) LD50 for rabbits: 4,000 mg/kg (DFGOT vol.13 (1999), SIDS (2002), BUA 70 (1991), HSDB (Access on June 2019))
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	Category 3	Danger	H331	P304+P340 P403+P233 P261 P271 P311 P321 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 3. Besides, because the exposure concentration was lower than 90% of the saturated vapor concentration (6,711 ppm), the reference value in units of ppm was applied as a vapor with little mist. [Evidence Data] (1) LC50 (4 hours) for rats: 1,000 ppm (SIDS (2002), HSDB (Access on June 2019)) (2) LC50 (4 hours) for rats: 4.2 mg/L (about 1,005.9 ppm) (BUA 70 (1991)) [Reference Data, etc.] (3) 4-hour inhalation with rats: all animals survived at 1,000 ppm (ACGIH (7th, 2001), OEL Documentations (Japan Society For Occupational Health (JSOH), 1990), SIDS (2002), BUA 70 (1991)) (4) 4-hour inhalation with rats: all animals died at 2,000 ppm (ACGIH (7th, 2001), OEL Documentations (Japan Society For Occupational Health (JSOH), 1990), SIDS (2002), BUA 70 (1991)) (5) 4-hour inhalation with rats: all animals survived at 1,000 mL/m3 (1,000 ppm) (DFGOT vol.13 (1999)) (6) 4-hour inhalation with rats: all animals died at 2,000 mL/m3 (2,000 ppm) (DFGOT vol.13 (1999))
1	Acute toxicity (Inhalation: Dusts and mists)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
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)-(4), it was classified in Category 1. [Evidence Data] (1) This substance is a severe irritant to the eyes, mucous membranes and skin, and severe burns and vesiculation of the skin were reported from liquid splashes (ACGIH (7th, 2001)). (2) In a skin irritation test with rabbits, under occluded conditions for 24 hours, it caused severe burns and blisters (ACGIH (7th, 2011)). (3) This substance is corrosive to the skin, eyes and mucous membranes (SIDS (2002)). (4) This substance is severely irritating to the skin and eyes, and direct contact with the liquid may result in burns (OEL Documentations (Japan Society For Occupational Health (JSOH), 1990), HSDB (Access on June 2019)). [Reference Data, etc.] (5) It was reported that it was mildly irritative in a skin irritation test in which 0.5 mL of this substance was applied to rabbits for 24 hours (DFGOT vol.13 (1999), SIDS (2002)). (6) It was classified in Skin Irrit. 1B (H314) in the EU CLP Classification (EU CLP classification (Access on July 2019)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Based on (1)-(5), it was classified in Category 1. [Evidence Data] (1) In an eye irritation test in which 0.005 mL of a 5% solution was applied to rabbits, the substance was strongly irritative (DFGOT vol.13 (1999)). (2) This substance is a severe irritant to the eyes, mucous membranes and skin, and severe burns and vesiculation of the skin were reported from liquid splashes. In addition, the vapor at 5 ppm is irritating to the eyes and upper respiratory tract. Damage to the eye is characterized as immediate burning, followed by an increasing severity of reaction with corneal and conjunctival edema (ACGIH (7th, 2001)). (3) This substance is a strong irritant or corrosive substance. Depending on the exposure concentration, burning in the eye, lacrimation, edema of the cornea and of the conjunctiva and corneal clouding occur. Severe corrosion of the cornea can lead to blindness (DFGOT vol.13 (1999)). (4) This substance is severely irritating to the skin and eyes and causes burns on direct contact with the liquid (OEL Documentations (Japan Society For Occupational Health (JSOH), 1990), HSDB (Access on June 2019)). (5) It is classified in Category 1 in skin corrosion/irritation.
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	*	- -	-	-	[Rationale for the Classification] Although there are descriptions shown in (1) and (2), the details cannot be confirmed. Therefore, classification was not possible due to lack of data. [Reference Data, etc.] (1) It is described that a response was indicative of sensitization reaction in a skin sensitization test with guinea pigs (0.05 mL administered intradermally twice per week for 2-2.5 weeks, challenged by a 25% solution) (ACGIH (7th, 2011), SIDS (2002)). (2) There is a sensitizing effect on the skin (OEL Documentations (Japan Society For Occupational Health (JSOH), 1990)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), since results of all standard combination tests, including in vivo and in vitro tests, were negative, it was classified as "Not classified." [Evidence Data] (1) As for in vivo, a negative result was reported for a micronucleus test with rat bone marrow cells (SIDS (2002), ACGIH (7th, 2001)). (2) As for in vitro, negative results were reported for a bacterial reverse mutation test and a mouse lymphoma assay (DFGOT vol.13 (1999), SIDS (2002), ACGIH (7th, 2011), NTP DB (Access on June 2019)).
6	Carcinogenicity	*	- -	-	-	[Rationale for the Classification] Based on the classification results by other organizations shown in (1), it was classified as "Classification not possible" in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in A4 by ACGIH (ACGIH (7th, 2011)). [Reference Data, etc.] (2) As a result of a retrospective cohort study of workers in a chemical plant producing this substance and acetic acid (CAS RN 64-19-7), a hydrolysis product of this substance, the SMR (standardized mortality ratio) for death from prostate cancer was 330 (deaths from prostate cancer: 6 observed versus 1.8 expected), but the exposure level was below the limit of detection for this substance (0.1-1.2 ppm for acetic acid), and there was no association with the duration of exposure (ACGIH (7th, 2011)).
7	Reproductive toxicity	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Besides, based on (3), acetic acid (CAS RN 64-19-7), the hydrolysis product of this substance, is considered not to cause developmental toxicity. [Reference Data, etc.] (1) In a screening test of a developmental toxicity test with female rats exposed by inhalation on Days 6-15 of gestation, total resorption was observed in 2 out of 4 animals at a concentration where maternal toxicity (severe respiratory tract irritation and body weight reduction) was observed (SIDS (2002)). This data was insufficient because the number of pregnant animals was only 4. (2) It was described that abnormalities in the offspring were produced in a developmental toxicity test by intraperitoneal injection into mice on days 11 to 13 of pregnancy, but there is no information on maternal effects or specific effects in offspring (SIDS (2002)). (3) It was described that acetic acid, the hydrolysis product of acetic anhydride, was not teratogenic to rabbits in an oral study in which 5% acetic acid was administered orally to rabbits on Days 6-18 of gestation (SIDS (2002)).
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory organs)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on the human reports in (1)-(3), it was classified in Category 1 (respiratory organs). Based on the information in (4), in the previous classification, it was classified in Category 3 (narcotic effects), but this was not adopted because the details were unknown. Therefore, the classification result was changed. Besides, effects on the blood system were reported in humans following ingestion of a large amount of acetic acid (CAS RN 64-19-7) as shown in (5), but it is unlikely that similar effects will occur with this substance. [Evidence Data] (1) In humans, exposure to vapor concentrations at or above 5 ppm causes irritation of the eyes and upper respiratory tract. Exposure to high vapor concentrations may produce ulceration of the nasal mucosa and bronchospasms (DFGOT vol.13 (1999), ACGIH (7th, 2011)). (2) A 22-year-old male dye worker suffered severe burns on 35% of his body surface by exposure to this substance as a result of an explosion of a drum containing the substance. Although the burns healed within three weeks, the damage leading initially to pulmonary edema progressed to bilateral pneumothoraces and bronchopulmonary fistula. The patient died about two months after the incident and fibrous adhesions were observed in the pleural cavity at autopsy (ACGIH (7th, 2011), HSDB (Access on June 2019)). (3) Workers exposed to aerosols of this substance and acetic acid in an industrial accident showed severe irritation of the eyes and upper respiratory tract, harsh cough, and breathing difficulties. Of the 18 workers admitted to the hospital, 14 showed severe conjunctivitis and acute pharyngolaryngitis, 12 had corneal opacities, 11 had nasal burns, 12 exhibited reactive airways distress syndrome, but all of the workers recovered within 5-25 days (ACGIH (7th, 2011), HSDB (Access on June 2019)). [Reference Data, etc.] (4) Exposure to high concentrations of this substance in humans resulted in depression of the central nervous system with drowsiness, dizziness and narcosis (SIDS (2002)). (5) There are multiple case reports that acetic acid, the hydrolysis product of this substance, affected the blood system (disseminated intravascular coagulopathy, severe hemolysis) in humans following ingestion of large amount (ACGIH (7th, 2004), PATTY (6th, 2012)). However, there were no reports of similar effects after inhalation. As for this substance, there are no reports on oral exposure in humans, and it is described that oral intake of the aggressively odoriferous solution is improbable (GESTIS (Access on September 2019)). As for the other routes, there were no reports of effects on the blood system including the accidental exposure in (2) and (3).
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), it is classified in Category 1 (respiratory organs). [Evidence Data] (1) In a study in which rats were exposed by inhalation to the vapor at 1-20 ppm for 13 weeks (6 hours/day, 5 days/week), histopathological findings showing mild irritation of the respiratory tract (nasal cavity, larynx, trachea) were observed at 5 ppm (converted guidance value: 0.015 mg/L, within the range of Category 1), and symptoms indicating eye and respiratory tract irritation, body weight reduction and histopathological findings indicating mild to moderate irritation of the respiratory tract (nasal cavity, larynx, trachea, lung) were found at 20 ppm (converted guidance value: 0.06 mg/L, within the range of Category 1). The histopathological changes observed were mainly localized inflammatory lesions with epithelial hyperplasia and/or squamous metaplasia (SIDS (2002), ACGIH (7th, 2011)).
10	Aspiration hazard	*	- -	-	-	[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)	-	- -	-	-	-
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.

To GHS Information