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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	5064-31-3
Chemical Name	Trisodium 2,2',2''-nitrilotriacetate
Substance ID	24A6141
Classification year (FY)	FY2012
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)	Physical Hazards and Health Hazards: GHS Classification Guidance by the Japanese Government (July, 2010) Environmental Hazards: UN GHS Document (4th 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.
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 > 200 deg C (IUCLID (2000)).
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 classified	- -	-	-	There is a metal (Na) present in the molecule, but from data: water solubility of 93 g/100 mL (20 deg C) (ICSC (J) 2003), it is estimated that it does not react vigorously with water.
13	Oxidizing liquids	Not applicable	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	Classification not possible	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded to the element other than carbon or hydrogen (Na). However, the classification is not possible due to no data.
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure.
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	It was classified in Category 4 based on a report on an LD50 value of 1,100 mg/kg bw for rats (Environmental Risk Assessment for Chemical Substances vol. 4 (Ministry of the Environment, 2005)). Besides, as for health hazards, also refer to nitrilotriacetic acid (CAS: 139-13-9), the free acid of this substance.
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	No data available.
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Solid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	No data available.
1	Acute toxicity (Inhalation: Dusts and mists)	Not classified	- -	-	-	It was classified as "Not classified" based on an LC50 value of > 5 mg/L/4 hours for rats (IUCLID (2000)). Besides, because the test concentration was higher than the saturated vapour pressure concentration (1.12E-08 mg/L), a reference value for dust was applied.
2	Skin corrosion/irritation	Not classified	- -	-	-	It was classified as "Not classified" because no skin reactions were observed after 24, 48, and 72 hours in a test by a 4-hour occlusive application to the rabbit skin, and it was not irritating (OECD TG 404, GLP) (IUCLID (2000)).
3	Serious eye damage/eye irritation	Category 2	Warning	H319	P305+P351+P338 P337+P313 P264 P280	In a test in which 50 mg of powders of this substance (purity 70%) was applied to the rabbit eye, erythema, edema, and corneal opacity were observed after 1 and 24 hours, erythema persisted after eight days, and it was irritating (IUCLID (2000)). Therefore, it was classified in Category 2. Besides, it is reported that it was not irritating in a test with rabbits on an aqueous solution (30%) of this substance (OECD TG 405, GLP) (IUCLID (2000)).
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.
4	Skin sensitization	Classification not possible	- -	-	-	No data available. Besides, it is reported that in a patch test on a 1% aqueous solution of a liquid detergent containing 20% of this substance in 66 human volunteers, irritation was very slight, and there was also no sensitization (Environmental Risk Assessment for Chemical Substances vol. 4 (Ministry of the Environment, 2005)).
5	Germ cell mutagenicity	Not classified	- -	-	-	As for tests on this substance, it is reported that it did not induce micronuclei or aneuploidy in cell genetic tests with bone marrow cells of mice (intraperitoneal administration) (in vivo somatic cell mutagenicity test) (IARC 73 (1999)). On the other hand, the expert's judgment on the free acid of this substance (nitrilotriacetic acid) was that there was no clear evidence of in vivo somatic cell mutagenicity. Therefore, it was regarded that there was also no clear evidence of mutagenicity of this substance, the trisodium salt, and it was classified as "Not classified" by the expert's judgment. Besides, as for in vitro tests on this substance, it is reported that it was negative in all of an Ames test (NTP DB (1987), IUCLID (2000)), a mouse lymphoma test (NTP DB (1987)), an HGPRT test with Chinese hamster V79 cells (IUCLID (2000)), and chromosomal aberration tests with CHO cells or human lymphocytes (IUCLID (2000)), and positive in a micronucleus test with Chinese hamster fetal lung cells (IUCLID (2000)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	It was classified in Category 2 because it was classified in Group 2B for carcinogenicity by IARC (IARC 73 (1999)), and Group 2B by the Japan Society For Occupational Health (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2012)). Besides, it is reported that in a test by 24-month or 18-month diet administration (followed by 6-month observation, only for 18-month administration) of the monohydrate of this substance to rats, and a test by 18-month diet administration (followed by 3-month observation) of the monohydrate to mice, tumors developed in the kidney, ureter, and urinary bladder in the high dose groups in both animal species, and carcinogenicity in the urinary tract was observed (NTP TR 6 (1977)).
7	Reproductive toxicity	Not classified	- -	-	-	In a reproductive test by two-generation diet administration to rats (doses: 0.1, 0.5%), slightly decreased food consumption and a trend toward a developmental delay were observed in parent animals in the 0.5% group, but there were neither fertility effects in both generations, nor increased malformations, nor effects on the development of offspring (Environmental Risk Assessment for Chemical Substances vol. 4 (Ministry of the Environment, 2005), ICCLID (2000)). On the other hand, in developmental toxicity tests by oral administration to pregnant rabbits, mice, or rats during the organogenesis period, no embryotoxicity or fetotoxicity was found, there was no increase in the incidence of malformations, and no adverse effects on the development of offspring were seen (Environmental Risk Assessment for Chemical Substances vol. 4 (Ministry of the Environment, 2005), ICCLID (2000)). From the above, because no adverse effects on sexual function and fertility or adverse effects on the development of offspring were observed in any test, it was classified as "Not classified."
8	Specific target organ toxicity - Single exposure	Category 2 (systemic toxicity)	Warning	H371	P308+P311 P260 P264 P270 P405 P501	In multiple acute oral toxicity tests with rats (LD50 value: 1,740-3,900 mg/kg), signs such as unbalanced body position, staggering, convulsions, and tonic seizure were observed in addition to dyspnea and apathia (IUCLID (2000)). And after oral administration to monkeys (0.5, 1, 2.0 g/kg), deaths occurred at or above 1 g/kg, and the animals died soon after showing paralysis following to decreased motor activity (IUCLID (2000)). No deaths were found at 5 mg/L (4 hours) in an inhalation exposure test with rats, but the animals showed salivation, hypoactivity, and labored breathing (IUCLID (2000)). From the above, deaths occurred after oral administration within the guidance value range for Category 2, but because it was hard to specify the target organ, it was classified in Category 2 (systemic toxicity).
9	Specific target organ toxicity - Repeated exposure	Category 2 (kidney)	Warning	H373	P260 P314 P501	It is reported that in a 2-year diet administration test with rats (doses: 0.03, 0.15, 0.5%), slight nephrosis consisting of edematous degeneration in the renal tubules was observed in the groups at or above 0.15% (75 mg/kg/day) corresponding to the guidance value range for Category 2 from the observation after six months, the incidence and severity increased with time, showing a significant difference, and it was severe at 0.5% (Environmental Risk Assessment for Chemical Substances vol. 4 (Ministry of the Environment, 2005)). Therefore, it was classified in Category 2 (kidney). Besides, it is described that lesions in the kidney in a 90-day diet administration test with rats were slight hydropic degeneration, atrophy, and dilatation in the renal tubules in the 750 mg/kg/day group, swelling and irregular surfaces of the kidney, hydronephrosis (by histopathological examination) in the 2,000 mg/kg/day group, and they became marked at the high dose (Environmental Risk Assessment for Chemical Substances vol. 4 (Ministry of the Environment, 2005)). On the other hand, it is reported that in a 28-day repeated inhalation exposure test with rats (0.01, 0.21, 0.34 mg/L/6 hours/day), there were no treatment-related toxicity findings other than dyspnea seen at the highest dose during the exposure period, and there were no treatment-related toxicity findings also in a 90-day repeated dermal administration test with rabbits (administration concentration: 2.5% (50 mg/kg bw/day)) (IUCLID (2000)).
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.

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	It was classified in Category 3 from 96-hour EC50 = 98 mg/L for crustacea (Gammarus pseudolimnaeus) and 96-hour LC50 = 98 mg/L for fish (Oncorhynchus mykiss) (EU, 2005).
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 being rapidly degradable (a degradation rate by DOC: 100% (EU, 2005)), and 147-day NOEC = 9.3 mg/L for crustacea (Gammarus pseudolimnaeus) (EU, 2005). 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" from 96-hour EC50 > 560 mg/L for algae (Chlorella vulgaris) (EU, 2005), and being not water-insoluble (water solubility = 1,000,000 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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