GHS Classification Result （Revision of the past classification result）

Chemical Name：Phthalonitrile
CAS：91-15-6

Result：
ID: 22B4504
Classifier: Ministry of Health, Labour and Welfare （MHLW）, Ministry of the Environment （MOE）
Year Classified: FY2010
Reference Manual: GHS Classification Guidance by the Japanese Government （July, 2010）

PHYSICAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement 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 - - - - There is a description that its autoignition temperature is > 580 degC (ICSC (Oct. 2004)) and it is considered that the substance does not ignite at room temperature.
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 - - - - Organic compounds containing no oxygen, fluorine or chlorine
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 Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
1 Acute toxicity （Oral） Category 3 Danger H301: Toxic if swallowed P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P321: Specific treatment （see ... on this label）.
P330: Rinse mouth.
P405: Store locked up.
P501: Dispose of contents/container to ... 		Three LD50 values for rats of 85 mg/kg ("Toxicity Testing Reports of Environmental Chemicals"(Chemicals Investigation Promoting Council) (Access on Jun. 2009)), 125 mg/kg and 30 mg/kg (both from SIDS (2001)) were reported. Based on the value of 85 mg/kg, which was obtained from the study complied with OECD Guideline (TG 401) and GLP with high reliability, the substance was classified as Category 3.
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 - - - - Although the test was carried out under the test condition of the saturated vapor atmosphere with low dust formation (SIDS (2001)), the LC50 value was not measured. Therefore, the substance was classified as "Classification not possible".
1 Acute toxicity （Inhalation: Dusts and mists） Classification not possible - - - - No data available.
2 Skin corrosion/irritation Not classified - - - - The substance was classified as "Not classified" based on the documented case of "not irritating" resulted from the rabbit test that application of 50% aqueous emulsion for 1 minute up to 20 hours (SIDS (2001)). As relevant information, 24-hour application of 1% or 10% solution to the inside of the forearm of humans did not induce skin irritation (IUCLID (2000)). On the other hand, there was the information that the substance caused irritation (SIDS (2001)). However, since it was finally concluded as "not irritating" (SIDS (2001)), and reference was old, the information was not adopted.
3 Serious eye damage/eye irritation Not classified - - - - The substance was classified as "Not classified" based on the documented case of "not irritating" resulted from the rabbit test in which 0.1 mL of undiluted substance was instilled to rabbit's eye (SIDS (2001)).
4 Respiratory sensitization Classification not possible - - - - No data available.
4 Skin sensitization Classification not possible - - - - No data available.
5 Germ cell mutagenicity Not classified - - - - The substance was classified as "Not classified" based on the negative results in the micronucleus test using bone marrow obtained from mice orally administered (in vivo mutagenicity test in somatic cells) (SIDS (2001)). As relevant information, as for in vitro studies, negative results in the Ames test ("Toxicity Testing Reports of Environmental Chemicals"(Chemicals Investigation Promoting Council) (Access on Jun. 2009)), negative results in the gene mutation test using Chinese hamster V79 cells (SIDS (2001)) and positive results in the chromosome aberration test using Chinese hamster CHL cells (SIDS (2001)), were reported.
6 Carcinogenicity Classification not possible - - - - Insufficient data were available. As relevant information, in the oral, dermal or subcutaneously administration tests using rats and mice, the tumors were observed. However, no evidence of the incidences of tumors in the concurrent control group or the background data of the control groups was described, so that the data were reported to be unreliable (SIDS (2001)).
7 Reproductive toxicity Classification not possible - - - - In the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test by oral administration in rats (0, 1, 6 and 30 mg/kg/day), all dams of the high dose group (30 mg/kg) died at the late stage of pregnancy. However, no adverse effects on sexual functions and fertility of parental animals were observed at any dose groups, and no treatment-related changes were observed with respect to the general condition, viability index, and external findings in neonate ("Toxicity Testing Reports of Environmental Chemicals"(Chemicals Investigation Promoting Council) (Access on Jun. 2009)). However, since data concerning the influence on the development of fetus containing the teratogenicity were insufficient, the substance was classified as "Classification not possible".
8 Specific target organ toxicity - Single exposure Category 1 (central nervous system) Danger H370: Causes damage to organs (central nervous system) P307+P311: IF exposed: Call a POISON CENTER or doctor/physician.
P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P321: Specific treatment （see ... on this label）.
P405: Store locked up.
P501: Dispose of contents/container to ... 		As the result of the acute oral study in rats, deaths occurred at dose levels more than 60 mg/kg corresponding to Category 1, the signs observed included convulsions, staining around the mouth, reduced locomotor activity, abnormal gait, prone position, vocalization, straub tail and cyanosis ("Toxicity Testing Reports of Environmental Chemicals" (Chemicals Investigation Promoting Council) (Access on Jun. 2009)). Moreover, it was also reported that the main effect of the substance was neurotoxicity (SIDS (2001)) and that the effects on central nervous system were remarkable (SIDS (2001)). Based on the information, the substance was classified as Category 1 (central nervous system).
9 Specific target organ toxicity - Repeated exposure Category 1 (nervous system), Category 2 (testis, eye) Danger
Warning 		H372: Cause damage to organs through prolonged or repeated exposure (nervous system)
H373: May cause damage to organs through prolonged or repeated exposure (testis, eye) 		P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P314: Get medical advice/attention if you feel unwell.
P501: Dispose of contents/container to ... 		Based on the reports describing that ten of 20 workers exposed occupationally in the manufacturing plant of phthalodinitrile during the several months to 2 years caused sudden consciousness disturbances and clonic convulsions, bradycardia and transient retrograde amnesia on the occasion of stroke (Sangyo Cyudoku Binran, 2nd ed. (1994), original report: Ueda, H. Yokohama Igaku, 11 (1961)), and that three of 32 workers engaged in the work handling phthaladonitrile revealed consciousness disturbances with sudden convulsions at 3 to 8 months after the initiation of work (Sangyo Cyudoku Binran, 2nd ed. (1994), original report: Ministry of Labor, Department of Safety and Hygiene, Section of Rodo Eisei, Rodo Eisei, 6 (1965)), the substance was classified as Category 1 (nervous system). In the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test by oral administration in rats (OECD TG 422, GLP-compliant), the effects on the nervous system was also suggested by the fact that convulsions occurred in all females in the high dose group (30 mg/kg/day) during the days from the gestation day (GD) 19 to GD23, then died. In the study, moreover, centrilobular hypertrophy of hepatocytes in the liver, hyaline droplet deposition and basophilic tubules in the proximal tubular epithelium of the kidneys, appearance of cell debris and loss of sperm in the ductus epididymis accompanied by atrophy of the seminiferous tubules of the testis were also observed in males of the same dose group ("Toxicity Testing Reports of Environmental Chemicals" (Chemicals Investigation Promoting Council) (Access on Jun. 2009)). In the 13-week feeding study in rats (OECD TG 408, US EPA guideline), furthermore, in addition to hyaline droplet formation in the renal tubules in males, clouding of the lens (cataract) were observed in both sexes at the dose levels equivalent to approx. 10 mg/kg/day on Week-13, which could not be detected on Week-4 (SIDS (2001)). As the results described above, the effects on the testis were observed at 30 mg/kg/day (converted value as that of 90-day study: 14.7 mg/kg/day) in the combined repeated oral dose and reproductive/developmental toxicity study (44-day treatment) and cataract was also observed at the dose levels over 10 mg/kg/day in the 13-week feeding study. Based on the information, the substance was classified as Category 2 (testis, eye). In addition, it was considered that hypertrophy of hepatocytes was possibly related to the change by induction of hepatic enzymes ("Toxicity Testing Reports of Environmental Chemicals" (Chemicals Investigation Promoting Council) (Access on Jun. 2009)), and that the renal changes were similar to nephropathy which was caused by male-rat specific alpha-2-micro globulin and were species-specific lesions ("Toxicity Testing Reports of Environmental Chemicals" (Chemicals Investigation Promoting Council) (Access on Jun. 2009)). Thus, neither of them was evidenced to classify.
10 Aspiration hazard Classification not possible - - - - No data available.

ENVIRONMENTAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
11 Hazardous to the aquatic environment （Acute） Category 3 - - H402: Harmful to aquatic life P273: Avoid release to the environment.
P501: Dispose of contents/container to ... 		Classified into Category 3 from its 96h-LC50 = 22.6 mg/L for fish (Oryzias latipes) (SIDS, 2003).
11 Hazardous to the aquatic environment （Long-term） Category 3 - - H412: Harmful to aquatic life with long lasting effects P273: Avoid release to the environment.
P501: Dispose of contents/container to ... 		Classified into Category 3 since its acute toxicity is Category 3 and it is not rapidly degradable (BOD degradation rate: 3.3% (Biodegradation and Bioconcentration of Existing Chemical Substances under the Chemical Substances Control Law, 1981)).
12 Hazardous to the ozone layer Classification not possible - - - - This substance is not listed in Annexes to the Montreal Protocol.


NOTE:
* 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.

Reference：
Reference Manual
Definitions / Abbreviations
Model Label by MHLW

 MHLW Website （in Japanese Only）
Model SDS by MHLW

 MHLW Website （in Japanese Only）

To GHS Information