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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	62-44-2
Chemical Name	4'-Ethoxyacetanilide; Phenacetin
Substance ID	23B5505
Classification year (FY)	FY2011
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)	Physical Hazards & 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	Classification not possible	- -	-	-	No data available.
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to solid (melting point <= 140 deg C) substances are not 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.
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	There are two LD50 values for rats (1,650 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)) and about 4,000 mg/kg (IARC 24 (1980))), one corresponds to Category 4, and the other corresponds to "Not classified." By adopting the category with higher hazard, it was classified in Category 4.
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)	Classification not possible	- -	-	-	An LC50 value of 33.9 mg/L for mice (Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)) was obtained, but because the exposure time is unknown, the classification is not possible.
2	Skin corrosion/irritation	Classification not possible	- -	-	-	No data available.
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	No data available.
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.
4	Skin sensitization	Classification not possible	- -	-	-	No data available.
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	It was classified in Category 2 because it is reported to be positive in micronucleus tests with bone marrow or peripheral blood after oral or intraperitoneal administration to mice or oral administration to rats (in vivo somatic cell mutagenicity tests) (IARC 100A (2011)). Besides, it is also reported to be positive in DNA damage tests with mouse kidney or rat urinary bladder (in vivo somatic cell genotoxicity test) (IARC 100A (2011)). On the other hand, as for in vitro tests, it is reported that Ames tests gave both negative and positive results (NTP DB (Access on Aug. 2011), IARC 24 (1980)), a mouse lymphoma test was negative (NTP DB (Access on Aug. 2011)), and a chromosomal aberration test with cultured Chinese hamster cells was positive (IARC 100A (2011)).
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	It was classified in Category 1A because IARC classified it in Group 1 for carcinogenicity (IARC 100A (2011)). Besides, it was classified in R by NTP (NTP RoC (12th, 2011)) and B2 by EPA (HSDB (2011)). In humans, there are many reports of pelvic and urothelial tumors in patients who used large amounts of analgesics containing this substance (IARC 100A (2011)), and in epidemiological studies, it is reported that a highly increased relative risk of cancers of the renal pelvis and ureter associated with regular use of drugs containing this substance was observed, and a statistically significant dose-response relationship of increasing risk with increasing consumption of this substance was shown (IARC 100A (2011)). Also, in an animal test, increased incidences of cancers in the kidney and urinary bladder were reported after diet administration to rats (Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)).
7	Reproductive toxicity	Classification not possible, Additional category: Effects on or via lactation	- -	H362	-	An epidemiological survey in humans monitored 50,282 mother-child pairs, 5,546 of which had exposure to this substance during the first trimester, and anomalies and defects such as craniosynostosis (six cases), adrenal syndromes (five), anal atresia (seven), accessory spleen (five) were reported, but it is described that the statistical significance of these is unknown, and independent confirmation is required (HSDB (2009)). As for animal tests, it is mentioned that in a test by oral administration to females rats on gestational days 0-20, decreased gestation index was observed in the dosed groups (Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)), but the knowledge was old (1965), and the details are unknown. There is no other information, and from the above, it was classified as "Classification not possible" due to lack of data of effects on sexual function, fertility, and the development of offspring. On the other hand, this substance is known to be excreted into breast milk in humans (HSDB (2009)), and it is described that lactation should be stopped when nursing mothers are dosed because it is reported that a suckling infant developed methemoglobinemia (drug manufacturer's information). Therefore, it was classified in the Additional category: Effects on or via lactation.
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	It is mentioned that this substance has effects on the central nervous system, including relieving tension and removing anxiety, in addition to an analgesic action (Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)), and it is described convulsions, coma, circulatory collapse, respiratory failure, and death may result from overdoses of this substance or aspirin, and such central nervous system effects have been reported following ingestion of average to large doses (NTP TR 67 (1978)). Therefore, it was classified in Category 1 (central nervous system).
9	Specific target organ toxicity - Repeated exposure	Category 1 (kidney, blood)	Danger	H372	P260 P264 P270 P314 P501	This substance had been used as an antipyretic and analgesic drug, but its supply was voluntarily stopped upon a request to prevent abuses. Many reports show adverse renal effects of exposure to this substance in humans as follows. A high incidence of renal papillary necrosis (56.5%) was observed in an epidemiological survey in persons who abused this substance in Australia (Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)), a significant increase in death from diseases of the urinary system or kidney was found in women who had taken this substance for ten years or longer in Switzerland (Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)), and risk of kidney diseases was highest in regular users of this substance in a survey of analgesic use in the United States (Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)). Therefore, it was classified in Category 1 (kidney). Furthermore, as side effects of this substance, a decrease in platelets, hemolytic anemia, and gastric/duodenal hemorrhage are described (Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)), chronic abuse may cause poisoning, death, and a high incidence of anemia (HSDB (2009)), and there is a case report in which taking a preparation containing this substance for ten years induced sulfhemoglobinemia with cyanosis in a 40-year-old woman (HSDB (2009)). Therefore, it was classified in Category 1 (blood). Besides, as for animal tests, it is reported that in a test with male rats orally dosed at 2 g/kg/week for 220 days, 80% of the animals was azoospermic on Day 176 (Environmental Risk Assessment for Chemical Substances vol. 3 (Ministry of the Environment, 2004)), but it was not used for the rationale for classification because the dose exceeded the guidance values for Category 2.
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)	Classification not possible	- -	-	-	No data available.
11	Hazardous to the aquatic environment (Long-term)	Classification not possible	- -	-	-	No data available.
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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