GHS Classification Result

Chemical Name：4'-Hydroxyacetanilide
CAS：103-90-2

Result：
ID: 1-335
Classifier: Ministry of Economy, Trade and Industry （METI）, Ministry of the Environment （MOE）
Year Classified: FY2008
Reference Manual: GHS Classification Guidance by the Japanese Government （Sep, 2008）

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 molecules.
2 Flammable gases （including chemically unstable gases） Not applicable - - - - Solid
3 Aerosols Not applicable - - - - Not aerosol products
4 Oxidizing gases Not applicable - - - - Solid
5 Gases under pressure Not applicable - - - - Solid
6 Flammable liquids Not applicable - - - - Solid
7 Flammable solids Classification not possible - - - - Classification not possible due to lack of data
8 Self-reactive substances and mixtures Not applicable - - - - There are no chemical groups associated with explosive or self-reactive properties present in the molecule.
9 Pyrophoric liquids Not applicable - - - - Solid
10 Pyrophoric solids Not classified - - - - Even if it contacts the normal temperature air, it does not ignite spontaneously (ignition temperature 540degC (Merck KGaA data from March 2009)).
11 Self-heating substances and mixtures Classification not possible - - - - Classification not possible due to lack of data
12 Substances and mixtures which, in contact with water, emit flammable gases Not applicable - - - - Metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At) are not included.
13 Oxidizing liquids Not applicable - - - - Solid
14 Oxidizing solids Not applicable - - - - Although it is an organic compound including oxygen, not fluorine and chlorine, this oxygen has not chemically bound to any elements other than carbon and hydrogen.
15 Organic peroxides Not applicable - - - - The organic compound not including peroxy group in molecule.
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） Not classified - - - - LD50 value 3,700 mg/kg of the oral administration test employing a rat (IARC 73 (1999)), which corresponded to the U.N. GHS acute toxicity Category 5, fell under unadopted category in Japan and was classified into "Not classified".
1 Acute toxicity （Dermal） Classification not possible - - - - Classification not possible due to lack of data
1 Acute toxicity （Inhalation: Gases） Not applicable - - - - Since it was a solid by the definition of GHS and inhalation in gas was not assumed, it was classified into "Not applicable".
1 Acute toxicity （Inhalation: Vapours） Classification not possible - - - - Classification not possible due to lack of data
1 Acute toxicity （Inhalation: Dusts and mists） Classification not possible - - - - Classification not possible due to lack of data
2 Skin corrosion/irritation Classification not possible - - - - Although "not irritating" is described for the skin irritation/corrosion test using rabbits (OECD TG 404, GLP) in IUCLID that is the information source of List 2, classification is not possible due to insufficient data, because there is no information in List 1 nor other negative study results I available.
3 Serious eye damage/eye irritation Classification not possible - - - - Although, in IUCLID (2000) which is the resource of List 2, there is a description of "not irritating" in the eyes irritation/corrosion test employing the rabbit (OECD TG 405, GLP), since there is no information in List 1and no other negative test result is obtained, classification is not possible due to insufficient data.
4 Respiratory sensitization Classification not possible - - - - Classification is not possible since there is no data.
4 Skin sensitization Classification not possible - - - - Classification is not possible since there is no data.
5 Germ cell mutagenicity Category 2 Warning H341: Suspected of causing genetic defects P308+P313: IF exposed or concerned: Get medical advice/attention.
P201: Obtain special instructions before use.
P202: Do not handle until all safety precautions have been read and understood.
P281: Use personal protective equipment as required.
P405: Store locked up.
P501: Dispose of contents/container to ... 		There are descriptions of "negative" (IARC 73 (1999)) in the productive cell in vivo mutagenicity test (chromosome aberration test employing the spermatocyte of a mouse), "positive" (IARC 73 (1999))NTP TR394 (1993)) as body cell in vivo mutagenicity test in the chromosome aberration test employing human peripherals lymphocytes, " positive" (IARC 73 (1999), NTP TR394 (1993)) in the micronucleus test using human buccal mucosa cells, "positive" (IARC 73 (1999)) in the chromosome aberration test employing the bone marrow cell of a mouse, "negative" (IARC 73 (1999)) in the micronucleus test using the bone marrow cell of a mouse, and "positive" (IARC 73 (1999)) in the body cell in vivo genotoxicity test (SCE test employing human blood). As mentioned above, although there was data of two or more body cell in vivo mutagenicity tests, since there was no positive data of a productive cell in vivo genotoxicity test, it was classified into Category 2. In addition, there are descriptions of "negative" (IARC 73 (1999) (IUCLID (2000)) in the reverse mutation test employing Salmonella typhimurium as an in vitro mutagenicity test and "negative" (IUCLID (2000)) in the reverse mutation test employing coli bacteria.
6 Carcinogenicity Not classified - - - - Since it was estimated the group 3 (IARC 73 (1999)) by IARC, according to guidance, it was classified into "Not classified". In addition, the two-year oral administration test employing male and female rats and male and female mice shows a description that "No carcinogenicity findings was acknowledged in male and female mice and male rats, however, the increase in a development-of-symptoms rate of mononuclear cell leukemia was seen in the high-dose group of female rats" (IARC 73 (1999), NTP TR 394 (1993)).
7 Reproductive toxicity Classification not possible - - - - There is a description about humans based on a large scale cohort study and case study as follows, "There is no report on teratogenicity caused by this substance" (IARC 73 (1999)). Moreover, there is a description as follows, "Although low body weight and body weight decrease in the child animals in the administered group were observed at birth and increase in the development ratio of sperm abnormality in the group with high level administration was observed, there is no effect on reproductive functions" in the reproduction evaluation study based on a continuous reproduction study via oral administration using mice (NTP TR394 (1993)). On the other hand, since there is also a description as follows, "The number of cleft palates, skeletal deformation and development of hydronephrosis increased depending on dose levels" (IUCLID (2000)) in the oral administration study with female mice during 6-15 days of pregnancy, classification is not possible.
8 Specific target organ toxicity - Single exposure Category 1 (liver, kidney, central nervous system, heart, digestive system), Category 2 (respiratory system, testis) Danger
Warning 		H370: Causes damage to organs (liver, kidney, central nervous system, heart, digestive system)
H371: May cause damage to organs (respiratory system, testis) 		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 ...
P309+P311: IF exposed or if you feel unwell: Call a POISON CENTER or doctor/physician. 		IARC73 (1999) and NTP TR394 (1993) have a report that "hepatotoxicity and nephrotoxicity were foreseen" in the oral administration test which used multiple human cases and animals (rats, mice, dogs). Moreover, HSDB (2007) has descriptions that "confusion, a temperature fall, inactivity, shallow respiration, arrhythmia, a blood-pressure fall, and inadequate circulations may occur followed by excitement and mental confusions, " as a symptoms, that "symptom advances in four steps: The 1st step - loss of appetite, nausea, vomit, sense of discomfort, diaphoresis, the 2nd step - an abdominal pain, tenderness, enlarged liver, a bilirubin elevation, increasing liver enzymes concentrations, prolonged prothrombin time, oliguria depending on the case, the 3rd step - loss of appetite, nausea, vomit, the recurrence of sense of discomfort, liver failures, kidney failures, cardiomyopathy, and the 4th step - recovery or liver failures that results fatality", and that "excessive dosage may cause the increase of gastrointestinal ulcers and bleeding risk by epidemiological study". In animal studies, on the other hand, there is a description that "the necrosis was looked at by the bronchial epithelium and the testis in addition to the effect on liver and kidney" in the oral administration test employing a mouse (IARC 73 (1999)), and such symptoms were foreseen within the limits of the guidance value of Category 2. As mentioned above, it was classified into Category 1 (liver, the kidney, a central nervous system, the heart, digestive system) and Category 2 (the respiratory system, testis). In addition, HSDB (2007) has a warning reporting that "skin reactions including the spots-like papular eruption accompanied by pruritus and hives occurs" by dosing it, and a description that "the reaction pharynx part dropsy, blood vessel nature dropsy, and like an anaphylaxis may occur rarely." as a sensitivity reaction.
9 Specific target organ toxicity - Repeated exposure Category 1 (liver, kidney, blood system), Category 2 (thyroid) Danger
Warning 		H372: Cause damage to organs through prolonged or repeated exposure (liver, kidney, blood system)
H373: May cause damage to organs through prolonged or repeated exposure (thyroid) 		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 ... 		For humans, there is a report that "chronic active hepatitis accompanies chronic ingestion and chronic kidney disease accompanies prolonged use" (NTP TR394 (1993)). There are also reports from human epidemiological studies that "toxicity was shown" (IARC 73 (1999)), "an increase in kidney lipofuscinosis, chronic kidney disease and hemolytic anemia through excessive long-term ingestion were observed" (Patty (5th, 2001)) and "neutropenic and thrombocytopenic disorders were observed" (HSDB (2007)). Therefore the liver, kidney and blood system are considered to be target organs. Furthermore, in a 2-year oral administration study in rats and mice (21 CFR Part 58, GLP) there is a report that "increased severity of nephropathy in male and female rats, increased frequency of localized kidney tubule hyperplasia and kidney hyperparathyroidism in male rats, and increased thyroid follicular epithelial hyperplasia in male and female mice were observed" (NTP TR394 (1993)), and these effects are seen to be within the range of guidance values for Category 2. For the reasons stated above, we classified it as Category 1 (liver, kidney and blood system) and Category 2 (thyroid). As for observed effects which are outside the range of guidance values for Category 2, there is a report that "at 12,500 ppm (corresponding value: 625 mg/kg) testis atrophy and at 25,000 ppm (corresponding value: 1,250 mg/kg) ovarian and uterine atrophy were observed" in a 13-week oral administration study in rats (NTP TR 394 (1993)).
10 Aspiration hazard Classification not possible - - - - Classification not possible due to lack of data

ENVIRONMENTAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
11 Hazardous to the aquatic environment （Acute） Category 2 - - H401: Toxic to aquatic life P273: Avoid release to the environment.
P501: Dispose of contents/container to ... 		It was classified into Category 2 from 48 hours EC50=3.5mg/L of the crustacea (Daphnia magna) (Environmental Agency eco-toxicity tests of chemicals (1998)).
11 Hazardous to the aquatic environment （Long-term） Category 2 - H411: Toxic to aquatic life with long lasting effects P273: Avoid release to the environment.
P391: Collect spillage.
P501: Dispose of contents/container to ... 		Although acute toxicity was Category 2, since there were no data about rapid degradability, it was classified into Category 2.


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
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Model SDS by MHLW

 MHLW Website （in Japanese Only）

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