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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	107-66-4
Chemical Name	Di-n-butyl phosphate
Substance ID	R01-B-019
Classification year (FY)	FY2019
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)	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)	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	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2	Flammable gases	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	*	- -	-	-	From data on a flash point of 187 deg C (open cup) (ICSC (1998)), it is estimated to be higher than 93 deg C also in the prescribed closed-cup method. Therefore, it was classified as "Not classified."
7	Flammable solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
8	Self-reactive substances and mixtures	*	- -	-	-	There are no chemical groups associated with explosive or self-reactive properties present in the molecule. It was classified as "Not classified (Not applicable)."
9	Pyrophoric liquids	*	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from an autoignition temperature of 420 deg C (ICSC (1998)).
10	Pyrophoric solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
11	Self-heating substances and mixtures	*	- -	-	-	Classification is not possible because test methods applicable to liquid substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	It contains a metalloid (P), but it was classified as "Not classified" because it is estimated that it does not react vigorously with water from water solubility data of 1.72*104 mg/L (25 deg C) (HSDB (Access on May 2019)).
13	Oxidizing liquids	*	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded to an element (P) other than carbon or hydrogen. However, the classification is not possible due to no data.
14	Oxidizing solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	No data available.
17	Desensitized explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: 3,200 mg/kg (SIDS (2004), HSDB (Access on August 2019)) (2) LD50 for rats: >2,000 mg/kg (REACH registration dossier (Access on August 2019)) [Reference Data, etc.] (3) Minimum lethal dose in rats (purity: 62.6% (impurities: monobutyl phosphate: 18.3%, tributyl phosphate, etc.: 19.1%)): >2,000 mg/kg (JECDB (Access on June 2019))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Category 1	Danger	H314	P301+P330+P331 P303+P361+P353 P305+P351+P338 P304+P340 P260 P264 P280 P310 P321 P363 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 1. Besides, the category was changed due to the new data obtained. [Evidence Data] (1) In an in vitro skin corrosion test using an artificial human epidermis model (EST-1000) in compliance with OECD TG 431, following 3 minutes and 60 minutes of exposure, cell viabilities were 64% and 2%, respectively (REACH registration dossier (Access on July 2019)). [Reference Data, etc.] (2) It was highly irritating in a skin irritation test in which 0.5 mL was administered semi-occlusively to the ears of rabbits for 8 hours (ACGIH (7th, 2009), SIDS (2004)). (3) This substance may cause irritation of the skin in humans (HSDB (Access on June 2019)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Based on the data in (1)-(3) and the fact that it was classified in "Skin Corrosion (Category 1)," it was classified in Category 1. Besides, the category was changed due to the new data obtained. [Evidence Data] (1) In an eye irritation test in which 0.1 mL was administered to rabbits, it produced corrosion of the cornea (ACGIH (7th, 2009)). (2) In an eye irritation test in which 0.1 mL was applied into the eyes of rabbits and observed for 7 days, the mean scores for corneal opacity, the iris, conjunctiva, and chemosis were 1,5, 1, 2 and 2.8, respectively. Besides, they did not resolve completely within 7 days (REACH registration dossier (Access on July 2019)). (3) In an in vitro skin corrosion test using an artificial human epidermis model (EST-1000) in compliance with OECD TG 431, it was judged to be a corrosive substance (Category 1) (REACH registration dossier (Access on July 2019)). [Reference Data, etc.] (4) This substance may irritate the eyes, nose, throat and lungs of humans (HSDB (Access on June 2019)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." Besides, the category was changed due to new data obtained. [Evidence Data] (1) No skin reaction was observed in a skin sensitization test (guinea pig maximization test) with guinea pigs according to OECD TG 406, and it was judged to be negative for sensitization (REACH registration dossier (Access on July 2019)). (2) No sensitization was shown in a test with guinea pigs (ACGIH (7th, 2009)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] There are no in vivo data. Therefore, classification was not possible due to lack of data. [Evidence Data] (1) As for in vitro, there are reports of negative results in a bacterial reverse mutation test and a mammalian cell chromosomal aberration test (JECDB (Access on June 2019), ACGIH (7th, 2009), SIDS (2004)).
6	Carcinogenicity	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
7	Reproductive toxicity	*	- -	-	-	[Rationale for the Classification] No teratogenicity was observed in (1). However, there is no information on fertility and sexual function. Therefore, classification was not possible due to lack of data. The classification result was changed due to reviewing the evidence data for the classification based on the purity of the test substance, etc. [Evidence Data] (1) There is a report that no maternal or fetal toxicity was observed in a developmental toxicity test with female rats administered orally on gestational days 7-17 (ACGIH (7th, 2009)). [Reference Data, etc.] (2) In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422) in which rats were administered with a mixture containing this substance (this substance: 62.6%, monobutyl phosphate: 18.3%, and tributyl phosphate and others: 19.1%) by gavage, in parental animals, death or sacrifice in extremis (male: 3/10 animals, female: 2/10 animals), emaciation, deep and slow respiration, erosion and ulceration of the urinary bladder and stomach mucosa, and hepatocellular hypertrophy, etc. were observed. As for reproductive effects, one female had dystocia with death of all pups, but no apparent reproductive effects were observed. As for developmental effects, a tendency of decreases in the number of live births, live birth index, the number of live pups and viability index on day four of lactation are reported (JECDB (Access on June 2019), SIDS (2004), ACGIH (7th, 2009)).
8	Specific target organ toxicity - Single exposure	Category 3 (Respiratory tract irritation)	Warning	H335	P304+P340 P403+P233 P261 P271 P312 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 3 (respiratory tract irritation). In the previous classification, it was classified in Category 3 (narcotic effects) based on the findings observed in the test with rats in (3). However, these findings are inadequate as a rationale for classification. In addition, the purity of this substance in the test substance is low, and the effects of impurities could not be assessed. Therefore, the classification was changed from the previous classification. [Evidence Data] (1) This substance is a moderately strong acid and is considered to be irritating to the skin, eyes, mucus membranes and the respiratory tract (ACGIH (7th, 2009)). [Reference Data, etc.] (2) There is information that workers exposed to this substance complained of respiratory tract irritation and headaches (ACGIH (7th, 2001)). However, the original source is a personal communication with no details, and this information is not listed in the ACGIH (7th, 2009). (3) In a test in which rats were dosed by single oral gavage at 2,000 mg with this substance (purity: 62.6% (impurities: monobutyl phosphate: 18.3%, tributyl phosphate and others: 19.1%)), a transient decrease in locomotor activity, deep and slow respiration, blepharoptosis, salivation, urine contamination on the lower abdomen and red urine were observed, but there were no deaths, and no abnormal findings were also observed at autopsy (JECDB (Access on June 2019)).
9	Specific target organ toxicity - Repeated exposure	*	- -	-	-	[Rationale for the Classification] Based on (1), there is a report that by oral administration to rats, effects on the liver, adrenal gland and urinary bladder were observed within the range of Category 2. However, the purity of this substance in the test substance is low, and the effects could be caused by other components. Therefore, it was classified as "Classification not possible." By reviewing based on the purity of the test substance, etc., the classification result was changed from the previous classification. [Reference Data, etc.] (1) In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in which rats were gavaged at 30-1,000 mg/kg/day (purity: 62.6% (impurities: monobutyl phosphate: 18.3%, tributyl phosphate and others: 19.1%)) for 44 days in males and 40-51 days in females, damage of the urinary bladder and stomach mucosa (erosion or ulceration in the glandular stomach mucosa and forestomach mucosa) was observed at or above 100 mg/kg/day (converted guidance value: 49/44 mg/kg/day for male/female, within the range of Category 2) or 300 mg/kg/day (converted guidance value: 147/133 mg/kg/day for male/female, exceeding Category 2), and hepatocyte fatty change and vacuolation of the adrenocortical cells were observed in females whose entire litter died at or above 100 mg/kg/day (JECDB (Access on June 2019), SIDS (2004), ACGIH (7th, 2009)).
10	Aspiration hazard	*	- -	-	-	[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 Short term (Acute)	Not classified	- -	-	-	It was classified as "Not classified" from 96-hour LC50 = 110 mg/L for fish (Oryzias latipes) (SIDS, 2004).
11	Hazardous to the aquatic environment Long term (Chronic)	Not classified	- -	-	-	Reliable chronic toxicity data were not obtained. Because it is not rapidly degradable (a degradation rate by BOD: average 2% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1994)), and due to 96-hour LC50 = 110 mg/L for fish (Oryzias latipes) (SIDS, 2004), then it is classified as "Not classified." From the above results, it was classified as "Not classified."
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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.
An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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