NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	552-30-7
Chemical Name	1,2,4-Benzenetricarboxylic 1,2-anhydride
Substance ID	H26-B-090, R-038
Classification year (FY)	FY2014
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)
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	Classification not possible	- -	-	-	No data available. Besides, it is described that it is combustible (ICSC (2005)).
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 that it does not ignite at normal temperatures from an autoignition temperature of 740 deg C (GESTIS (Access on September 2014)).
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data available.
12	Substances and mixtures which, in contact with water, emit flammable gases	Not applicable	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At).
13	Oxidizing liquids	Not applicable	- -	-	-	Solid (GHS definition).
14	Oxidizing solids	Not applicable	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule
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)	Not classified	- -	-	-	Based on reports of LD50 values of 2,730 mg/kg (male, female) (2,030 mg/kg (female), 3,340 mg/kg (male)) (CICAD (2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2003)) and >2,730 mg/kg (OEL Documentations (Japan Society For Occupational Health (JSOH), 1998)) for rats, it was classified as "Not classified" (Category 5 in UN GHS classification).
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Based on reports of an LD50 value of 5,600 mg/kg for rats (CICAD (2009), SIDS (2003)) and of LD50 values of >2,000 mg/kg (CICAD (2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2003)) and >23,000 mg/kg (OEL Documentations (Japan Society For Occupational Health (JSOH), 1998)) for rabbits, it was classified as "Not classified."
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)	Not classified	- -	-	-	Based on reports of LC50 values (4 hours) of >2.33 mg/L (CICAD (2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2003), OEL Documentations (Japan Society For Occupational Health (JSOH), 1998)) and >7.4 mg/L (Environmental Risk Assessment for Chemical Substances Vol.7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009), ACGIH (7th, 2001)) for rats, it was classified as "Not classified." Besides, since LC50 values were higher than 90% of the saturated vapor concentration (<0.77 mg/L), the reference values in units of mg/L were applied as a vapour with a mist. New information sources (CICAD (2009), Environmental Risk Assessment for Chemical Substances Vol.7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2003), ACGIH (7th, 2001), OEL Documentations (Japan Society For Occupational Health (JSOH), 1998)) were added, and the category was revised.
2	Skin corrosion/irritation	Not classified	- -	-	-	There is a description that in a study in which 500 mg of this substance was applied to rabbits for 4 hours, slight irritation was observed but this irritation resolved after 14 days (SIDS (2003), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). From the above result, it was judged to be "Not classified" (Category 3 in UN GHS classification). The category was changed according to the revision of the GHS classification guidance for the Japanese Government.
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	It is described that in an eye irritation test (Draize method) with rabbits, the irritation score reached a maximum value (110/110) and it was considered severely irritating (SIDS (2004)). In addition, it is described that in another eye irritation test with rabbits, it was severely irritating (ACGIH (7th, 2001), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). From the above results, it was classified in Category 1.
4	Respiratory sensitization	Category 1A	Danger	H334	P304+P340 P342+P311 P261 P284 P501	Multiple allergic respiratory diseases such as asthma were reported among workers handling this substance (SIDS (2004), OEL Documentations (Japan Society For Occupational Health (JSOH)), 1998), and there is a description that allergic respiratory diseases were observed in 29% of workers handling this substance (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). In addition, this substance was classified as "RSEN" in ACGIH (7th, 2014), and as Occupational Sensitizers to the airway Group 1 by Japan Society For Occupational Health (JSOH). From the above results, it was judged to be Category 1A. Based on the description of occupational sensitizers to the airway Group 1 in OEL Documentations (Japan Society For Occupational Health (JSOH), 1998), it was subcategorized according to the description in the GHS classification guidance for the Japanese Government. Besides, this substance was classified as "R42" in the EU DSD classification, and as "Resp. Sens. 1 H334" in the EU CLP classification.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	There are reports that it was positive in a skin sensitization test with guinea pigs and a local lymph node assay (LLNA method) with mice (SIDS (2004), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ACGIH (7th, 2014)), and this substance was classified as "DSEN" by ACGIH. From the above, it was classified in Category 1. Besides, this substance was classified as "R43" in the EU DSD classification, and as "Skin Sens. 1 H317" in the EU CLP classification.
5	Germ cell mutagenicity	Classification not possible	- -	-	-	Classification not possible due to lack of data. There are no in vivo data. As for in vitro data, it was all negative in a bacterial reverse mutation test, a gene mutation test and a chromosome aberration test with cultured mammalian cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2004), HSDB (Access on August 2014), CICAD75 (2009), NTP DB (Access on September 2014), OEL Documentations (Japan Society For Occupational Health (JSOH), 1998)).
6	Carcinogenicity	Classification not possible	- -	-	-	Classification not possible due to lack of data.
7	Reproductive toxicity	Classification not possible	- -	-	-	Classification not possible due to lack of data. There are reports that no teratogenicity nor developmental toxicity was observed in teratogenicity tests with rats and guinea pigs by the inhalation route (ACGIH (7th, 2014), CICAD75 (2009), Environmental Risk Assessment for Chemical Substances Vol.7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2003)), and that no effects were observed in a teratogenicity test with mice by the oral route (CICAD75 (2009)). They were not adopted for classification because they were tests with only 1 dose. In addition, since information on fertility was not available, it was classified as "Classification not possible."
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory organs)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	This substance shows respiratory tract irritation (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009), OEL Documentations (Japan Society For Occupational Health (JSOH), 1998)). In humans, many cases were reported. Oral ingestion caused nausea, burning sensation, abdominal pain, vomiting and diarrhea, and inhalation exposure caused coughing, blood in the sputum, headache, nausea, breathlessness and wheezing (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.7, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009), OEL Documentations (Japan Society For Occupational Health (JSOH), 1998), SIDS (2004), ACGIH (7th, 2014), HSDB (Access on August 2014)). As for experimental animals, although labored breath was observed in an inhalation exposure (2.33 mg/L) with rats, and necropsy revealed red foci, mottled, and fluid filled in the lungs, and altered breathing patterns and temporary apneic event were observed by an inhalation exposure (0.002-0.15 mg/L) with mice, but it was reported that these symptoms may be attributable to direct stimulation of the vagal nerve endings in the deep lungs from this substance (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2004)). Based on pulmonary edema and severe effects such as stimulation of the vagal nerve endings in the deep lungs observed in experimental animals, this substance affected the respiratory organs, and it was classified in Category 1 (respiratory organs).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs, haemal system, immune system)	Danger	H372	P260 P264 P270 P314 P501	In humans, it was reported that respiratory diseases such as rhinitis, asthma, hypersensitivity pneumonitis, dyspnea and hemoptysis were caused by occupational inhalation exposure to fumes or the dust of this substance, and that the incidence could be significantly reduced by lowering the airborne concentration by improvement of the workplace environment. (ACGIH (7th, 2014), CICAD 75 (2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), OEL Documentations (Japan Society For Occupational Health (JSOH), 1999)). In addition, it is suggested that an immunological mechanism through the production of specific antibodies against this substance was involved in the occurrence of late respiratory systemic syndrome such as asthma and hypersensitivity pneumonia (ACGIH (7th, 2014), CICAD 75 (2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), OEL Documentations (Japan Society For Occupational Health (JSOH), 1999)). In experimental animals, in a study in which rats were exposed by inhalation to this substance (estimated as dusts) for up to 13 weeks, at concentrations within the range of Category 1 (0.002-0.05 mg/m3), a significant number of hemorrhagic lung foci and bronchopneumonia were observed, and increases in the lung weight and serum specific antibodies were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ACGIH (7th, 2014), SIDS (2004)). In experimental animals, the findings of lung damage via the humoral immunity mechanism were also obtained. On the other hand, by the oral route, in studies in which rats or dogs were dosed by feeding for 13 weeks, no clear hazardous findings on specific organs were observed even when doses exceeding Category 2 (equivalent to 500 mg/kg/day) were administered (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), CICAD 75 (2009), SIDS (2004)). From the above, based on the findings by the inhalation exposure in humans and experimental animals, it was classified in Category 1 (respiratory organs, blood system/immune system).
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	- -	-	-	It was classified as "Not classified" from 48-hour EC50 > 792 mg/L for crustacea (Daphnia magna), and 96-hour LC50 > 896 mg/L for fish (Leuciscus idus) (both SIDS, 2002, Initial Risk Assessment (NITE, CERI, NEDO, 2008)).
11	Hazardous to the aquatic environment (Long-term)	Not classified	- -	-	-	If chronic toxicity data are used, then it is classified as "Not classified" due to rapid degradability (a degradation rate by BOD: 96% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1988)), and 72-hour NOEC > 739 mg/L for algae (Pseudokirchneriella subcapitata) (SIDS, 2002, Initial Risk Assessment (NITE, CERI, NEDO, 2008)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified as "Not classified" because it was classified as "Not classified" in acute toxicity for both crustacea and fish and is not water-insoluble (water solubility = 1036 mg/L (PHYSPROP Database, 2009)). From the above results, it was classified as "Not classified."
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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