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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	84-69-5
Chemical Name	Diisobutyl phthalate
Substance ID	H30-B-008-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	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)	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	- -	-	-	Liquid (GHS definition)
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Liquid (GHS definition)
5	Gases under pressure	Not applicable	- -	-	-	Liquid (GHS definition)
6	Flammable liquids	Not classified	- -	-	-	A flash point is 169 deg C [unknown test methods] (GESTIS (Accessed Nov. 2018)). Even if it is the result from open-cup methods, a flash point is expected to be above 93 deg C in prescribed closed-cup methods. Therefore, it was classified as "Not classified."
7	Flammable solids	Not applicable	- -	-	-	Liquid (GHS definition)
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 classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 423 deg C (GESTIS (Accessed Nov. 2018)).
10	Pyrophoric solids	Not applicable	- -	-	-	Liquid (GHS definition)
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)
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)-(3), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: about 60,000 mg/kg (US Consumer Product Safety Commission (CPSC) (2011), BUA 201 (1997)) (2) LD50 for rats: 16,000-28,000 mg/kg (US CPSC (2011), BUA 201 (1997)) (3) LD50 for rats: > 5,000 mg/kg (PATTY (6th, 2012)) [Reference Data, etc.] (4) LD50 for mice: about 39,500 mg/kg (in BUA described as 37,100 mg/kg (converted value from 1.04 of the density)) (US CPSC (2011), BUA 201 (1997)) (5) LD50 for mice: > 12,800 mg/kg (US CPSC (2011), BUA 201 (1997))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) LD50 for guinea pigs: 10,400 mg/kg (US CPSC (2011)) (2) LD50 for guinea pigs: > 10,000 mg/kg (PATTY (6th, 2012))
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)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1)-(4), it was classified as "Not classified." [Evidence Data] (1) There is a report that this substance is not irritating in an in vitro test (OECD TG431, GLP-compliant) (REACH registration dossier (Accessed Dec. 2018)). (2) There is a report that in a skin irritation test with rabbits, in which the undiluted liquid of this substance was applied occlusively for 20 hours, after 7 days, the erythema score was 0.5 and the edema score was 0 (REACH registration dossier (Accessed Dec. 2018)). (3) There is a report that in a skin irritation test (OECD TG 404, n=3) with rabbits, no irritation was observed when the undiluted liquid of this substance was applied for 4 hours (BUA 201 (1997)). (4) There is a report that this substance is not skin irritating (Patty (6th, 2012)). [Reference Data, etc.] (5) There are reports that this substance is not irritating to the skin in rabbits and slightly irritating to the skin in guinea pigs (CPSC (2011)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1)-(4), it was classified as "Not classified." [Evidence Data] (1) There is a report that in an eye irritation test (OECD TG 405, n=3) with rabbits, no irritation was observed when the undiluted liquid of this substance was applied (BUA 201 (1997)). (2) There is a report that in an eye irritation test (n=2) with rabbits, no irritation was observed when the undiluted liquid of this substance was applied (REACH registration dossier (Accessed Dec. 2018)). (3) There are reports that in two eye irritation tests with rabbits, no irritation was observed in any tests (CPSC (2011)). (4) There is a report that this substance is not irritating to the eyes (Patty (6th, 2012)).
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] Since adequate information was not obtained to determine the sensitization of this substance, it was classified as "Classification not possible." Besides, since the number of animals is unknown in (1) and the details of the tests are unknown in (2) and (3), these were not used to determine the classification. [Reference Data, etc.] (1) There is a report that in a skin sensitization test (Kodak Drop-on method) with guinea pigs, as a result of induction and a challenge with a 0.1M solution of this substance (1:1:2 acetone:dioxane:corn oil), no skin sensitization was observed (REACH registration dossier (Accessed Dec. 2018)). (2) There is a study report that no sensitization was observed in a skin sensitization test with guinea pigs. However, since it was in-house data and no further details could be confirmed, it was described that adequate information was not obtained to determine the sensitization of this substance (US CPSC (2011)). (3) There is a report that this substance is not a skin sensitizer (PATTY (6th, 2012)). (4) There is a report that phthalates including this substance did not show skin sensitization in humans (NICNAS IMAP (Accessed Dec. 2018)).
5	Germ cell mutagenicity	Classification not possible	- -	-	-	[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, it was negative in multiple bacterial reverse mutation tests (PATTY (6th, 2012), US CPSC (2011), NICNAS IMAP (Accessed Dec. 2018)), and there is a positive result in a comet assay with human cells (US CPSC (2011), NICNAS IMAP (Accessed Dec. 2018)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] From (1), at doses without definite maternal toxicity, an increased fetal resorption and increased incidences of external, internal organs and skeletal malformations were observed as developmental effects, and from (2), at doses without maternal toxicity, findings suggesting anti-androgenic effects and delayed sexual maturation were observed in male pups, and damage to the testis and sperm, developmental disorders of genetic organs and increased malformations were observed in post-maturity males. Therefore, it was classified in Category 1B for this hazard class. [Evidence Data] (1) As a result of a teratogenicity test in which 250-1,000 mg/kg/day of this substance was administered by gavage on gestational day 6-20 of pregnant rats, in maternal animals, decreased body weight gain at or above 500 mg/kg/day without a significant difference in net body weight gain corrected for gravid uterine weights, and no other clear general toxic effects at up to the highest dose (1,000 mg/kg/day) were observed. An increased resorption ratio, increased incidences of external malformations (neural tube closure defects, anophthalmia), visceral malformations (urinary tract and vascular defects), and skeletal malformations (fused sternebrae and malformations of the vertebrae) in fetuses were found at or above 750 mg/kg/day, and an increased incidence of testicular descent failure was observed in male fetuses at 1,000 mg/kg/day (Proposal for identification of SVHC (2009), US CPSC (2011)). (2) As a result of a developmental toxicity study in which 125-625 mg/kg/day of this substance was administered by gavage on gestational day 12-21 to pregnant rats and offspring was observed for up to 122 days after birth, in the maternal animals, no abnormalities were observed at up to the highest dose (625 mg/kg/day). On the other hand, the pups showed degeneration of the seminiferous tubules of the testes (moderate to severe) and oligospermia or azoospermia in the epididymis in mature males at or above 125 mg/kg/day, decreased AGD (anogenital distance) in the male pups on postnatal day 1, retained areolas and nipples in the male pups on postnatal day 12-14, undeveloped or absent testes and epididymis in the matured males at or above 250 mg/kg/day, delayed preputial separation (could not be observed due to hypospadias in the highest dose group) at 500 mg/kg/day, and increased malformations (hypospadias, exposed os penis, non-scrotal testis) in the males at or above 500 mg/kg/day (Proposal for identification of SVHC (2009), US CPSC (2011)).
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Reference Data, etc.] (3) In a study of 85 pairs of mothers and boys, the levels of monoisobutyl phthalate (MIBP: primary metabolite of this substance) in the urine of the pregnant women were inversely correlated with the values of AGI (anogenital index) in the boys, and the incidence of cryptorchidism was high in the subgroup of the boys with an AGI below 25 percentiles for age, a small AGI. There are limitations such as the number of subjects, 85 subjects, is small and that since the measurement of MIBP in the urine of the mother was conducted only once, it does not necessarily reflect the average exposure level during the pregnancy period. However, this result is regarded as a report supporting the hypothesis that prenatal environmental phthalate exposure affects the development of the genetic organs in boys (Proposal for identification of SVHC (2009), US CPSC (2011)). (4) It was classified as "Repr. 1B" in the EU CLP classification and considered as SVHC candidate (Proposal for identification of SVHC (2009)).
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Besides, since the RTECS used as the evidence information source in the previous classification is in List 3, and the original source could not be identified, it was not adopted as the information source, and the category was changed.
10	Aspiration hazard	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Besides, based on (1), within the range of Category 1, effects on the testis were indicated in males, but this was not used for classification because it was data from only one animal. [Reference Data, etc.] (1) In a study with dogs (one male and one female) dosed by feeding for 2 months, a remarkable decrease in matured sperms was observed at 2.6 mg/kg/day (converted guidance value: 1.7 mg/kg/day) in the male (Proposal for identification of SVHC (2009), US CPSC (2011)). (2) In a study with rats dosed by feeding for 4 months, effects on blood, decreased testis weight and increased liver weight were observed in the 5% (equivalent to 3,500 mg/kg/day) group of the very high dose (Proposal for identification of SVHC (2009), US CPSC (2011)). (3) There are several reports of repeated dose studies which evaluated mainly the effects on the testis and liver in rats or mice using this substance or monobutyl phthalate, the metabolite of this substance (Proposal for identification of SVHC (2009), US CPSC (2011)). However, none of these studies meet the classification criteria in this hazard class based on the GHS classification guidance for the Japanese Government because they are short-term studies with a dose duration shorter than 2 weeks.

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)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 96-hour LC50 = 0.9 mg/L for fish (Pimephales promelas) (ECETOC TR91: 2003).
11	Hazardous to the aquatic environment (Long-term)	Category 3	- -	H412	P273 P501	It was classified in Category 3 due to rapid degradability (readily biodegradable, an average degradation rate by BOD: 98% (J-CHECK, 2001)), and 21-day NOEC (reproduction inhibition) = 0.11 mg/L for crustacea (Daphnia magna) (ECETOC TR91: 2003).
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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