NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	126-73-8
Chemical Name	Tri-n-butyl phosphate
Substance ID	R01-B-083
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	FY2014 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	*	- -	-	-	It was classified as "Not classified" from a flash point of 145 deg C (closed cup) (HSDB (Access on August 2019)).
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 present in the molecule associated with explosive or self-reactive properties. 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 > 480 deg C (ICSC (2005)).
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 data: it is poorly soluble in water (ICSC (2005)).
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)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] Based on (1)-(11), it was classified in Category 4. [Evidence Data] (1) LD50 for rats: 1,400 mg/kg (ATSDR (2012), EHC 112 (1991)) (2) LD50 for rats: 1,390-1,530 mg/kg (EHC 112 (1991)) (3) LD50 for rats: 1,552 mg/kg (EHC 112 (1991)) (4) LD50 for rats: 1,390-3,000 mg/kg (ACGIH (7th, 2001)) (5) LD50 for rats: 1,600-3,200 mg/kg (ATSDR (2012)) (6) LD50 for rats: 1,164-3,350 mg/kg (DFGOT vol.17 (2002)) (7) LD50 for rats: 1,390-3,350 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2004)) (8) LD50 for rats: 1,600-3,200 mg/kg (EHC 112 (1991)) (9) LD50 for rats: 3,160 mg/kg (ATSDR (2012)) (10) LD50 for rats: 3,200 mg/kg (ATSDR (2012)) (11) LD50 for rats: 3,000 mg/kg (EHC 112 (1991), Environmental Risk Assessment for Chemical Substances Vol. 4 (Ministry of the Environment, 2005)) (12) LD50 for rats: 1,390-11,265 mg/kg (PATTY (6th, 2012))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1)-(4), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: >3,100 mg/kg (PATTY (6th, 2012), ACGIH (7th, 2001), ATSDR (2012), DFGOT vol.17 (2002), EHC 112 (1991), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2004), Environmental Risk Assessment for Chemical Substances Vol. 4 (Ministry of the Environment, 2005)) (2) LD50 for rabbits: >4,640 mg/kg (ATSDR (2012), DFGOT vol.17 (2002)) (3) LD50 for rabbits: >5,000 mg/kg (ATSDR (2012)) (4) LD50 for rabbits: >10,000 mg/kg (PATTY (6th, 2012), DFGOT vol.17 (2002), SIDS (2004))
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)	Category 4	Warning	H332	P304+P340 P261 P271 P312	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 4. Besides, since the exposure concentration was higher than 90% of the saturated vapour concentration (about 0.016 mg/L), the reference value in units of mg/L was applied as the mist. The category was changed from the previous classification by the use of the new information sources. [Evidence Data] (1) LC50 (4 hours) for rats: >4,200 mg/m3 (4.2 mg/L) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2004)) (2) LC50 (6 hours) for rats: 123 ppm (1.34 mg/L) (converted 4-hour equivalent value: 2.01 mg/L) (ACGIH (7th, 2001)) (3) LC50 (6 hours) for rats: 1,359 mg/m3 (1.359 mg/L) (converted 4-hour equivalent value: 2.04 mg/L) (EHC 112 (1991)) [Reference Data, etc.] (4) LC50 (1 hour) for rats: 28,000 mg/m3 (28 mg/L) (converted 4-hour equivalent value: 7 mg/L) (ATSDR (2012) Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)) (5) LC50 (1 hour) for rats: <200,000 mg/m3 (200 mg/L) (converted 4-hour equivalent value: 50 mg/L) (ATSDR (2012))
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	[Rationale for the Classification] Based on (1)-(5), it was classified in Category 2. [Evidence Data] (1) In a skin irritation test with rabbits according to OECD TG404, slight irritation was observed (DFGOT vol.17 (2002), Hazard Assessment Report (CERI, NITE, 2007)). (2) By application of this substance (0.5 mL) to the skin of rabbits for 4 and 24 hours, mild irritation was observed (ATSDR (2012)). (3) In skin irritation tests with rabbits by application of this substance for 4 hours, slight or marked effects were observed (DFGOT vol.17 (2002)). (4) Application of this substance (0,01 mL) to the skin of rabbits showed irritation, and application of this substance (500 mg) to the intact or abraded skin of rabbits produced severe irritation (ACGIH (7th, 2001), EHC 112 (1991), Hazard Assessment Report (CERI, NITE, 2007)). (5) This substance had irritative effects on the respiratory organs, skin and eyes (DFGOT vol.17 (2002), PATTY (6th, 2012), GESTIS (Access on September 2019)). [Reference Data, etc.] (6) No irritative effects were found in a skin irritation test by application of this substance to rabbits for 24 hours (DFGOT vol.17 (2002)). (7) The skin irritation caused by this substance might be as serious as that caused by morpholine (Category 1) (EHC 112 (1991)). (8) It was classified as "Skin Irrit. 2 (H315)" by the EU CLP classification (EU CLP classification (Access on September 2019)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Based on (1)-(4), it was classified in Category 1. The category was changed from the previous classification because new data were obtained. [Evidence Data] (1) Necrosis was observed by applying this substance (0.02 mL) to the eyes of rabbits (ATSDR (2012)). (2) This substance had irritative effects on the skin, eyes and respiratory tract (DFGOT vol.17 (2002), PATTY (6th, 2012), GESTIS (Access on September 2019)). (3) Mild irritation with edema in the eyes was observed following instillation of this substance into the eyes (EHC 112 (1991)). [Reference Data, etc.] (4) In an eye irritation test with rabbits according to OECD TG 405, slight irritation was observed and was completely reversible within 14 days (DFGOT vol.17 (2002), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). (5) This substance was irritating to the skin and eyes of humans and experimental animals but did not cause sensitization in humans (SIAP (2001)). (6) Ocular injury was observed after application of this substance (ACGIH (7th, 2001)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to luck of data.
4	Skin sensitization	*	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) No skin reactions were observed in a skin sensitization test with guinea pigs (Buehler method), and sensitization was judged to be negative (DFGOT vol.17 (2002)). (2) Sensitization was judged to be negative in a skin sensitization test (OECD TG 406) with guinea pigs (GESTIS (Access on September 2019)). (3) Sensitization was judged to be negative in a skin sensitization test (Open Epicutaneous test) with guinea pigs (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). [Reference Data, etc.] (4) No skin reactions were observed in a patch test in which 53 volunteers were given 15 applications of this substance (<25% or> 25%) (HSDB (Access on September 2019), GESTIS (Access on September 2019)). (5) In a skin sensitization test with guinea pigs (details unknown), sensitization was observed with a positive rate of 42% (DFGOT vol.17 (2002)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), negative results of in vivo tests and some positive results of in vitro tests were reported. However, based on expert judgment, it was classified as "Not classified." [Evidence Data] (1) As for in vivo, there was a negative result in a chromosomal aberration test with rats (SIDS (2004), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), HSDB (Access on September 2019)). (2) As for in vitro, there were negative results in bacterial reverse mutation tests, a chromosomal aberration test, a gene mutation test and micronucleus tests with cultured mammalian cells (SIDS (2004), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol. 4 (Ministry of the Environment, 2005), DFGOT vol.17 (2002)), and there were positive results in some bacterial reverse mutation tests (TA1535, TA1538) (SIDS (2004), DFGOT vol.17 (2002), EHC 112 (1991)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 2. The classification result was changed from the previous classification by adding classification results by other organizations. [Evidence Data] (1) As for the classification results by domestic and international organizations, it was classified in Carc.2 by the EU CLP classification (EU CLP classification (Access on August 2019)). (2) In a study in which this substance was administered by feeding to mice for 1.5 years, the incidence of hepatocellular adenoma was significantly increased in males in the 3,500 ppm group (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). (3) In a study in which this substance was administered by feeding to rats for 2 years, a significant increase in the incidence of urinary bladder papilloma in both sexes and a significant increase in the incidence of transitional cell carcinoma in males were found (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)).
7	Reproductive toxicity	*	- -	-	-	[Rationale for the Classification] Based on (1)-(4), it was classified as "Not classified." [Evidence Data] (1) In a two-generation reproductive toxicity study with rats administered by feeding, pups showed only reduced body weights at doses where a reduction in body weights at doses where a reduction in body weights was observed in parental animals, and no effects on fertility were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2004), DFGOT vol.17 (2002)). (2) In a developmental toxicity study with female rats dosed by gavage on Days 6 to 15 of gestation, decreased body weight and an increased incidence of delayed ossification of the skull were seen in fetuses at a dose where maternal toxicity (decreased body weight, deaths (7/24 animals)) was observed, but no teratogenicity was noted (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2004), DFGOT vol.17 (2002)). (3) In a developmental toxicity study with female rats dosed by gavage on Days 7 to 17 of gestation, an increased incidence of the rudimentary lumbar ribs was seen at a dose where maternal toxicity (depression of body weight gain, decreased food consumption) was noted, but no teratogenicity was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2004), DFGOT vol.17 (2002)). (4) In a developmental toxicity study with female rabbits dosed by gavage on Days 6 to18 of gestation, no effects on fetuses were observed at a dose where maternal toxicity (body weight loss) was seen (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2004), DFGOT vol.17 (2002)).
8	Specific target organ toxicity - Single exposure	Category 2 (respiratory organs)	Warning	H371	P308+P311 P260 P264 P270 P405 P501	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 2 (respiratory organs). Regarding the pathological changes in the liver and kidney observed in (2), they were not used as target organs because details of findings in the liver were unknown, and findings in the kidney were observed only in dead animals. The classification result was changed from the previous classification by the use of the new information sources. Besides, in humans, there was information of (4), but the source was a private communication and details were unknown. [Evidence Data] (1) Based on several reports of acute inhalation toxicity studies in experimental animals, this substance was considered to be a strong respiratory irritant (SIDS (2004)). (2) In a 4-hour single inhalation exposure test with rats, the aerosol of this substance caused reduced motility, red tears and labored breathing at or above 72.5 ppm (0.8 mg/L) and loss of myotactic reflexes at or above 194 ppm (2.14 mg/L, corresponding to Category 2). Pathological changes in the lungs, liver, spleen, kidneys and gastrointestinal tract were observed in males at 384 ppm (4.24 mg/L, corresponding to category 2) at the autopsy carried out after the 28-day follow-up period (DFGOT vol.17 (2002), REACH registration dossier (Access on December 2019)). (3) In a 6-hour single inhalation exposure test with rats, after exposure to 123 ppm (1.36 mg/L, converted 4-hour equivalent value: 2.04 mg/L, corresponding to category 2), no mortality but severe irritation was seen in the skin and the respiratory tract (DFGOT vol.17 (2002), SIDS (2004), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). [Reference Data, etc.] (4) There was a report that some workers exposed to 0.015 mg/L of this substance complained of nausea and headache (ACGIH (7th, 2001), DFGOT vol.17 (2002), SIDS (2004), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (nervous system, urinary bladder)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 2 (nervous system, urinary bladder). Besides, degeneration of the seminiferous tubules observed in the 14-day test with rats which was the evidence in the previous classification was judged as an incidental finding because it was not confirmed either in an 18-week follow-up study by the same author or in other long-term studies with mice and rats. The classification result was changed from the previous classification by adding the new information sources and reviewing. [Evidence Data] (1) There was a report that in a 2-week repeated dose toxicity test with rats by gavage, a decrease in the nerve conduction velocity of the caudal nerve was revealed in males at 400 mg/kg/day (converted guidance value: 62 mg/kg/day, within the range of Category 2), and that examination with an electron microscope revealed no axonal degeneration in the sciatic nerve in both sexes but a retraction of Schwann cell processes surrounding the unmyelinated nerve fibers, and that the authors interpreted this as an early response to nerve damage (DFGOT vol.17 (2002), EHC (1991), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). (2) In a 13-week repeated dose toxicity test with rats by feeding, increased gamma-GT, increased liver weights and hyperplasia of the urinary bladder epithelium were seen in males at or above 1000 ppm (75 mg/kg/day, within the range of Category 2), and at 5,000 ppm (375 mg/kg/day, exceeding Category 2) reduced body weight gain, increased kidney weights and increased ALT in males and females, prolonged prothrombin time in males, and increased gamma-GT, increased liver weights and hyperplasia of the urinary bladder epithelium in females, were observed (DFGOT vol.17 (2002)). (3) In a two-year repeated dose toxicity study with rats by feeding, hyperplasia of the transitional epithelium of the urinary bladder, etc. were seen in both sexes at or above 700 ppm (male/female: 33/42 mg/kg/day, within the range of Category 2) (DFGOT vol.17 (2002), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)).
10	Aspiration hazard	*	- -	-	-	[Rationale for the Classification] Classification not possible due to luck 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)	Category 2	- -	H401	P273 P501	It was classified in Category 2 from 96-hour LC50 = 1.7 mg/L for crustacea (Gammarus pseudolimnaeus) (Initial Risk Assessment (NITE, CERI, NEDO, 2008), SIDS, 2004).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	It was classified in Category 2 because it was not rapidly degradable (a degradation rate by BOD: 0% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1980)), and due to 95-day NOEC = 0.82 mg/L for fish (Oncorhynchus mykiss) (Initial Risk Assessment (NITE, CERI, NEDO, 2008), SIDS, 2004).
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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