NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	7311-27-5
Chemical Name	11-(4-Nonylphenoxy)-3,6,9-trioxaundecan-1-ol (Nonoxynol-4 (p-form))
Substance ID	H30-A-007-METI, MOE
Classification year (FY)	FY2018
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/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)	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
UN GHS document (External link)	UN GHS document
Definitions/Abbreviations (Excel file)	Definitions/Abbreviations
Model Label by MHLW (External link)
Model SDS by MHLW (External link)
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	- -	-	-	Liquid (GHS definition) (Nonoxynol-4 is known as a liquid (J. Am. Coll. Toxicol., 2, 35-60 (1983)), and this substance can be estimated to be a liquid from the case of a mixture of o-, m-, and p-forms of the substance with the number of moles of added ethylene oxide: 9.5.)
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Liquid (GHS definition) (Nonoxynol-4 is known as a liquid (J. Am. Coll. Toxicol., 2, 35-60 (1983)), and this substance can be estimated to be a liquid from the case of a mixture of o-, m-, and p-forms of the substance with the number of moles of added ethylene oxide: 9.5.)
5	Gases under pressure	Not applicable	- -	-	-	Liquid (GHS definition) (Nonoxynol-4 is known as a liquid (J. Am. Coll. Toxicol., 2, 35-60 (1983)), and this substance can be estimated to be a liquid from the case of a mixture of o-, m-, and p-forms of the substance with the number of moles of added ethylene oxide: 9.5.)
6	Flammable liquids	Classification not possible	- -	-	-	No data available. Besides, a flash point is 282 deg C for a mixture of o-, m-, and p-forms of the substance with the number of moles of added ethylene oxide: 9.5 (Hazard Assessment Report (CERI, NITE, 2007)).
7	Flammable solids	Not applicable	- -	-	-	Liquid (GHS definition) (Nonoxynol-4 is known as a liquid (J. Am. Coll. Toxicol., 2, 35-60 (1983)), and this substance can be estimated to be a liquid from the case of a mixture of o-, m-, and p-forms of the substance with the number of moles of added ethylene oxide: 9.5.)
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	Classification not possible	- -	-	-	No data available.
10	Pyrophoric solids	Not applicable	- -	-	-	Liquid (GHS definition) (Nonoxynol-4 is known as a liquid (J. Am. Coll. Toxicol., 2, 35-60 (1983)), and this substance can be estimated to be a liquid from the case of a mixture of o-, m-, and p-forms of the substance with the number of moles of added ethylene oxide: 9.5.)
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid 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	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
14	Oxidizing solids	Not applicable	- -	-	-	Liquid (GHS definition) (Nonoxynol-4 is known as a liquid (J. Am. Coll. Toxicol., 2, 35-60 (1983)), and this substance can be estimated to be a liquid from the case of a mixture of o-, m-, and p-forms of the substance with the number of moles of added ethylene oxide: 9.5.)
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
16	Corrosive to metals	Classification not possible	- -	-	-	No data 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	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Besides, as for (2) and (3), isomer ratio information is unknown. [Evidence Data] (1) LD50 for male rats (Nonoxynol-4 (p-isomer)): 7,400 mg/kg (CIR (Cosmetic Ingredient Review) Expert Panel (2016), J. Am. Coll. Toxicol., 2, 35-60 (1983)). [Reference Data, etc.] (2) LD50 for male rats: 4,300 mg/kg (J. Am. Coll. Toxicol., 2, 35-60 (1983)). (3) LD50 for rats: 4,290-7,400 mg/kg (Canada PS Assessment report (2001)).
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified" (Category 5 in UN GHS classification). Besides, as for (2), isomer ratio information is unknown. [Evidence Data] (1) LD50 for rabbits (Nonoxynol-4 (p-isomer)): 2,550-2,575 mg/kg (calculated value from LD50: 2.5 mL/kg (J. Am. Coll. Toxicol., 2, 35-60 (1983)) and specific gravity: 1.02-1.03 (CIR Expert Panel (2016))) [Reference Data, etc.] (2) LD50 for rabbits: > 2,000 mg/kg (Canada PS Assessment report (2001))
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	[Rationale for the Classification] Liquid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Besides, although the saturated vapor concentration of this substance is unknown, the reference value as mist was applied based on the description that the test was conducted with 1% aerosol (with aqueous dispersant). [Evidence Data] (1) LC50 for rats (8 hours): > 21.7 mg/L (calculated from 0.0213 mL/L and specific gravity: 1.02-1.03, converted 4-hour equivalent value: > 43.4 mg/L, there was no death at 21.7 mg/L) (J. Am. Coll. Toxicol., 2, 35-60 (1983), CIR Expert Panel (2016))
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. Besides, although there are data (3) and (4) which showed this substance is not irritating to the skin, the reliability of these data is compared with the reliability of data (1) and (2), resulting in the judgment above based on the weight of evidence. [Evidence Data] (1) There is a report that as a result of repeated occlusive applications (3 times/week for 3 weeks, induction phase) of a 10% solution of Nonoxynol-4 (p-isomer) (in mineral oil) for 48 hours to the dorsal skin of 111 humans (10 men and 101 women), very slight to moderate erythema was observed in 36/111 (32.4%) (CIR Expert Panel (2016), J. Am. Coll. Toxicol., 2, 35-60 (1983), Canada PS Assessment report (2001)). (2) There is a report that in a skin irritation test with rabbits, as a result of an occlusive application of nonoxynol-4 (p-isomer) for 24 hours, in the 0.5 mL application group (n = 6) well-defined to severe erythema and slight to severe edema were observed in all the animals, and the primary irritation index (PII) was 5.58 based on the average score of erythema and edema at 24, 72 hours after the start of exposure (CIR Expert Panel (2016), J. Am. Coll. Toxicol., 2, 35-60 (1983)). (3) There is a report that in an irritation test in which undiluted Nonoxynol-4 (p-isomer) was applied to the dorsal skin of humans (each 25 men and women) for 48 hours at the first time and then 14 times every 24 hours repeatedly, no irritation was observed (CIR Expert Panel (2016), J. Am. Coll. Toxicol., 2, 35-60 (1983)). (4) There is a report that in a skin irritation test with rabbits, as a result of an occlusive application of nonoxynol-4 (p-isomer) for 24 hours, in the 0.01 mL application group (n = 5), no irritation was observed (CIR Expert Panel (2016), J. Am. Coll. Toxicol., 2, 35-60 (1983)).
3	Serious eye damage/eye irritation	Category 2A	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] Based on (1), it was classified in Category 2A according to the GHS Classification Guidance for the Japanese Government. Besides, (2) and (3) were not used for the classification judgement since in (2), the observation period was 24 hours, and in (3), the test substance concentration was low. [Evidence Data] (1) There is a report that in an eye irritation test (n = 6) with rabbits, as a result of application of undiluted 4-nonoxynol (p-isomer) solution, moderate irritation was observed in the cornea, iris, and conjunctiva, and did not resolve completely even after 7 days (CIR Expert Panel (2016), J. Am. Coll. Toxicol., 2, 35-60 (1983)). [Reference Data, etc.] (2) There is a report that in an eye irritation test (n = 5) with rabbits, as a result of application of the undiluted liquid of this substance, moderate irritation was observed after 24 hours (CIR Expert Panel (2016), J. Am. Coll. Toxicol., 2, 35-60 (1983)). (3) There is a report that in an eye irritation test (n = 6) with rabbits, as a result of application of a 5% preparation of this substance (moisturizing lotion), little irritation was observed (CIR Expert Panel (2016), J. Am. Coll. Toxicol., 2, 35-60 (1983)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] In tests on humans, there are reports (1) of no sensitization and (2) that sensitization was observed in a small number of people. However, it was judged that there is no evidence sufficient to judge whether it will be classified or not, and it was classified as "Classification not possible." [Reference Data, etc.] (1) There is a report as follows: the undiluted solution of Nonoxynol-4 (p-isomer) was applied to the dorsal skin of humans (each 25 men and women) for 48 hours at first and then 14 times every 24 hours repeatedly; although a response was provoked by 24-hour re-application 2 weeks after discontinuation of the application, no sensitization was observed (CIR Expert Panel (2016), J. Am. Coll. Toxicol., 2, 35-60 (1983)). (2) There is a report as follows: a 10% solution of nonoxynol-4 (p-isomer) (in mineral oil) was occlusively applied to the dorsal skin of 111 humans (10 men and 101 women) for 48 hours repeatedly (3 times/week for 3 weeks; induction phase), and after 2 weeks an occlusive patch (challenge) was applied for 48 hours; very slight to moderate erythema was observed in 36/111 subjects, and 3/36 subjects were diagnosed of allergic contact dermatitis; when retested (applied for 30 minutes) to the three subjects, allergic reaction was reproduced in only 1/3 subjects, and reaction was slight (CIR Expert Panel (2016), J. Am. Coll. Toxicol., 2, 35-60 (1983)).
5	Germ cell mutagenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Classification not possible" in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) As for in vivo, Nonoxynol-4 (isomer ratio is unknown) is reported as negative in a micronucleus test (intraperitoneal administration) with mouse bone marrow cells (Canada PS Assessment report (2001)). (2) As for in vitro, as for Nonoxynol-4 (isomer ratio is unknown), there are negative reports in both a bacterial reverse mutation test and an unscheduled DNA synthesis (UDS) test with rat primary hepatocytes (Canada PS Assessment report (2001)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] There are no available reports on humans for carcinogenicity. As for experimental animals, carcinogenicity is not reported for Nonoxynol-4 in (1) although the isomer ratio is unknown. In addition, there are also no classification results by domestic and international organizations. Therefore, it was classified as "Classification not possible" for this hazard class. [Evidence Data] (1) When Nonoxynol-4 (isomer ratio is unknown) was administered by feeding to rats at 200 mg/kg/day and to dogs at 40 mg/kg/day for 2 years, no carcinogenicity was observed (J. Am. Col. Toxicol., 2, 35-60 (1983), Canada PS Assessment report (2001), CIR Expert Panel (2016)). (2) There are no classification results by domestic and international organizations.
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Besides, (1) couldn't be used for classification since the doses where symptoms were observed are unknown. [Reference Data, etc.] (1) There is a report that in a single dermal dose test (dose: 1,020 mg/kg-6,798 mg/kg) with rabbits, erythema and necrosis of the skin were observed at various doses, and in dead animals, congestion and bleeding of the lung were observed (J. Am. Coll. Toxicol., 2, 35-60 (1983)).
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) and (2), this substance corresponds to "Not classified" by the oral route, but toxicity information on other routes is insufficient. Therefore, it was classified as "Classification not possible." [Evidence Data] (1) In tests in which Nonoxynol-4 (p-isomer) was administered by feeding to rats or dogs for 90 days, no effects were observed at doses within the range of Category 2, and growth retardation and increased liver weights in rats at 1,000 mg/kg/day and increased liver weights in dogs at 200 mg/kg/day were only observed (J. Am. Col. Toxicol., 2, 35-60 (1983), CIR Expert Panel (2016)). (2) In tests in which Nonoxynol-4 (p-isomer) was administered by feeding to rats or dogs for 2 years, no effects were observed at doses within the range of Category 2, and reduced body weights and enlarged liver in rats at 1,000 mg/kg/day and reduced body weights, vomiting, and increased serum ALP activity in dogs at 1,000 mg/kg/day were only observed (J. Am. Col. Toxicol., 2, 35-60 (1983), CIR Expert Panel (2016)).
10	Aspiration hazard	Classification not possible	- -	-	-	[Rationale for the Classification] 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)	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	- -	-	-	No data available.

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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