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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	80-54-6
Chemical Name	3-(4-tert-Butylphenyl)-2-methylpropanal
Substance ID	H30-B-012-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	FY2011
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	Category 4	- Warning	H227	P370+P378 P403+P235 P210 P280 P501	It was classified in Category 4 based on a flash point of 79 deg C (closed cup) (GESTIS (Access Dec. 2018)).
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 257 deg C (GESTIS (Access Dec. 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)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] Based on (1)-(3), two cases correspond to Category 4, and one corresponds to "Not classified" (Category 5 in UN GHS classification). By adopting a category with the largest number of cases, it was classified in Category 4. The category was changed by use of new information sources. [Evidence Data] (1) LD50 for rats: 1,390 mg/kg (male, female) (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018)) (2) LD50 for rats: 3,700 mg/kg (SCCS (2017)) (3) LD50 for rats: 1,000-2,000 mg/kg (male, female) (SCCS (2017))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: > 5,000 mg/kg (SCCS (2016)). (2) LD50 for rabbits: > 4,700 mg/kg (SCCS (2016)). (3) LD50 for rats: > 2,000 mg/kg (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018)).
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	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 according to the GHS Classification Guidance for the Japanese Government. As for (3), it is a result in support of judgment of Category 2 although the test method is not in accordance with OECD TG. [Evidence Data] (1) In a skin irritation test (OECD TG404, GLP-compliant, n = 3) with rabbits, as a result of the semi-occlusive application of the undiluted liquid of this substance for 4 hours, the mean scores at 24-72 hours for erythema and edema were 1.7/2.0/2.3 and 2.0/2.7/3.0, respectively, and the mean erythema and edema scores observed after 7 days were 1.7 and 1.3, respectively (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018), REACH registration dossier (Accessed Dec. 2018), ECETOC TR66 (1995)). In addition, PII (primary irritation index) was 4.56 (ECETOC TR66 (1995)). (2) There is a report that in a skin irritation test (equivalent to OECD TG404, GLP-compliant, n = 4) with rabbits, as a result of the semi-occlusive application of the undiluted liquid of this substance for 4 hours, the mean scores at 24-72 hours for erythema and edema were 1.7/2.0/2.0/2.0 and 1.0/1.7/1.7/2.3, respectively, and desquamation after 7 days was observed in all the animals (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018), ECETOC TR66 (1995)). In addition, PII (primary irritation index) was 3.58 (ECETOC TR66 (1995)). [Reference Data, etc.] (3) There is a report that in a skin irritation test (FDA Register 38. No. 187, Para. 1500.41, S27029, n = 2 (5 minutes, or 2-hour application), n = 3 (24-hour application), male (2) female (1)) with rabbits, as a result of the occlusive application of the undiluted liquid of this substance, the mean scores at 24-72 hours for erythema and edema of 2.0 and 1.0 at 5-minute application, 1.0, 2.0 and 1.0, 0.5 at 2-hour application were observed, the animals of the former (5 minutes application) recovered after 8 days, while in 1/2 the animals in the latter (2-hour application), erythema did not resolve, and desquamation of the skin was observed after 8 days in all the animals (REACH registration dossier (Accessed Dec. 2018)). (4) There is a report that in a patch test with 25 volunteers (men: 3, women: 22), as a result of 24-hour occlusive application of solutions of this substance (in 75% ethanol/25% diethyl phthalate) at concentrations of 0, 10, 15, 20, 25%, respectively, faint erythema was observed in a few subjects in the case of 10% and 20% solutions, but skin irritation was not observed at the highest concentration, and concentration dependence was not observed (SCCS (2016)).
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	[Rationale for the Classification] From (1)-(3), it was classified in Category 2B based on the information that it is reversible within 7 days. The category was changed from the previous classification by use of new information sources. [Evidence Data] (1) There is a report that in an eye irritation test (OECD TG405, GLP-compliant, n = 3) with rabbits, as a result of application of a 10 or 30% solution of this substance (solvent: diethyl phthalate), redness, edema, and discharge with score 1 were observed in the conjunctiva, but these disappeared within 7 days (SCCS (2016), NICNAS IMP (Accessed Dec. 2018)). (2) There is a report that in an eye irritation test (FDA Register 38. No. 187, Para. 1500.41, S27029, n = 3) with rabbits, as a result of application of the undiluted liquid of this substance, the average scores of conjunctival redness after 24, 48, and 72 hours were 0.5, 0.5, 1.0, respectively, and no corneal opacity, iritis, or conjunctival edema was observed (NICNAS IMP (Accessed Dec. 2018), REACH registration dossier (Accessed Dec. 2018)). (3) There is a report that in an eye irritation test (n = 6) with rabbits, as a result of application of an 8% solution of this substance (solvent: propylene glycol), very slight to severe edema in 4/6 animals and slight to moderate discharge in 3/6 animals were observed in the conjunctiva, but these resolved: within 4 days. Effects on the cornea were observed until 72 hours, but then these resolved. Effects on the iris were also observed, but these resolved: within 7 days (SCCS (2016)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] Based on (1)-(6), it was classified in Category 1.Besides, SCCS judged as shown in (7) because case reports of being positive were observed with low frequency although test conditions such as solvents may lead to positive reactions. [Evidence Data] (1) There are plural reports of repeated patch tests on volunteers (HRIPT method) including tests by applying up to a 25% concentration, most of which were reported to be negative. While most of these negative tests are tests using a mixed solvent of ethanol and diethyl phthalate, a HRIPT test using petrolatum as a solvent showed a positive reaction in 9/25 subjects at a 5% concentration (SCCS (2016)). (2) There is a report that in a patch test on patients of dermatology, a positive reaction against this substance was shown (11-100 cases/facility), and the positive rate of this substance at 5% concentration was 0-1.2% (in most, below 0.6%) (SCCS (2016)). (3) There is a report that positive results were obtained in four LLNA tests (OECD TG 443, GLP-compliant) with mice, but the EC3 value varied between 2.94% (ethanol) and 18.7% (acetone/olive oil (4: 1)) depending on the solvent, and in a test with ethanol as solvent (concentrations: 25, 10, 50, 100%), the SI value >=3 was obtained for all concentrations (3.3, 9.8, 24.3, 38.5), and concentration-dependence was found (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018)). (4) There is a report that in a Maximization test with guinea pigs (OECD TG 406, GLP-compliant, n = 5/sex), the animals showed a positive reaction against a solution (acetone/PEG 400) of this substance (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018)). (5) There is a report that in a Buehler test with guinea pigs (OECD TG 406, GLP-compliant, n = 10), a weakly positive reaction was shown against a solution (ethanol) of this substance (SCCS (2016)). (6) There is a report that in a Kao test with guinea pigs (n = 10/group), as a result of application of a 30% solution (ethanol) or undiluted solution of this substance, a positive reaction was shown in 5/10 animals in the former and in 6/10 animals in the latter (SCCS (2016)). [Reference Data, etc.] (7) In 2012, the SCCS expressed the opinion that this substance acts as a contact allergen in humans (established contact allergen in humans) (SCCS (2016), SCCS (2017)). (8) There is a report that in a Maximization test with guinea pigs (OECD TG 406, GLP-compliant, n=20), the animals did not show a positive reaction against a solution (ethanol) of this substance (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018)).
5	Germ cell mutagenicity	Classification not possible	- -	-	-	[Rationale for the Classification] The datum of the in vivo test is only (1). Therefore, classification was not possible due to lack of data. [Evidence Data] (1) As for in vivo, in a micronucleus test (OECD TG 474, GLP) with the bone marrow of mice, a significant increase in the ratio of polychromatic erythrocytes was observed after 48 hours in the highest dose group males, but the variation was within the range of the background data, so it was stated as no conclusion could be drawn (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018)). (2) As for in vitro, although a positive result was obtained in a mammalian chromosome aberration test, this substance was negative in bacterial reverse mutation tests and mammalian cell gene mutation tests (SCCS (2016, 2017), 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] In (1), adverse effects on the genetic organs in male animals and reproductive disorders (increased post-implantation resorption rate, no live pups obtained) were observed at doses where slight symptoms (increase in serum cholinesterase, increase in relative liver weight, and decreased body weight gain) occurred in the F0 parental animals. In the data of both (2) and (3), developmental effects were also observed in live pups and fetuses. Based on the above, it was classified in Category 1B based on reproductive effects and testicular toxicity manifested in one generation test. The category was changed by the use of new information sources. [Evidence Data] (1) In a one-generation study with rats dosed by feeding, decreased body weight gain and effects on the liver (increased relative weight, increased serum AST and ALP activity, etc.) were observed in the F0 parental animals treated with >= 1,700 ppm, and live pups were not obtained in these groups. In addition, as effects on the male reproductive organs, diffuse degeneration of the testes and azoospermia in the epididymis in the >= 1,700 ppm groups and hyperplasia of Leydig cells in the 3,400 ppm group were observed. As for the 2 lower dose groups (400, 800 ppm), increased serum cholinesterase, increased relative liver weight, decreased body weight gain, etc. were found in the F0 parent animals, and adverse effects on development and postnatal growth: increased post-implantation resorption rate, reduced body weight values at birth and weaning, decreased body weight gain were observed in the F1 pups (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018), CLP Report (2017)). (2) In an extended one-generation study (OECD TG 443, GLP-compliant) with rats dosed by feeding, no adverse effects on the parental fertility were observed even at 10 mg/kg/day where general toxic effects (decreased body weight gain, effects on the liver such as centrilobular hepatocytes hypertrophy, single cell necrosis, and periportal vacuolation) were observed in F0 and F1 parental animals. In addition, in F1 and F2 pups born in the 10 mg/kg/day group, lower body weight values and reduced peripheral acetylcholinesterase (AChE) activities in serum erythrocytes and diaphragm tissue (F1 male pups on postnatal day 4 and F1 female pups on postnatal day 76) were observed, then SCCS judged reduced AChE activities in peripheral tissues as adverse effects (SCCS (2017), CLH Report (2017)). (3) In a teratogenicity test (OECD TG 414, GLP-compliant) with rats dosed by gavage on gestational day 6-20 (organogenesis period), at up to 45 mg/kg/day where maternal toxicity was apparent, as developmental effects, reduced fetal body weight, delayed ossification, and soft tissue variations and skeletal variations were observed, but no increases in death or malformations were observed in the fetuses (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018), CLP Report (2017)).
8	Specific target organ toxicity - Single exposure	Category 3 (narcotic effects, respiratory tract irritation)	Warning	H336 H335	P304+P340 P403+P233 P261 P271 P312 P405 P501	[Rationale for the Classification] Since the respiratory tract irritation was adopted based on (1), and narcotic effects based on (2), it was classified in Category 3 (narcotic effects, respiratory tract irritation). The target organ was added by the use of new information sources. [Evidence Data] (1) As a result of measuring the respiratory rate for 30 seconds after an inhalation exposure in mice to this substance for 1-5 minutes, a concentration-dependent decrease in respiratory rate (up to 41.2%) was observed. This is considered to be the effect from irritation effects on the respiratory organs by this substance (SCCS (2016)). (2) In a single oral dose test with rats, somnolence (general depressed activity) and dyspnea were observed at or above the doses of 681 mg/kg. As for other symptoms, deterioration in general conditions, rough fur coat, abnormal gait, etc. are reported (NICNAS IMAP (Accessed Dec. 2018), SCCS (2016)). [Reference Data, etc.] (3) In the 2,000 mg/kg group of a single dermal application test with rats, dyspnoea, agitation, apathy, staggering gait, rough fur coat, lacrimation, and deterioration in general conditions in addition to local irritation were observed (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (genetic organs (men))	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on the data of (1)-(4), adverse effects on the male genetic organs and spermatogenesis of various species were observed. As the hazard category, based on the short-term (2 weeks) studies of (2) and (3), as a result of conversion by a number of days, these effects are within Category 1. However, the result of a 90-day oral administration study (OECD TG408, GLP) with rats, (1) was preferentially adopted according to the GHS Classification Guidance for the Japanese Government, and it was classified in Category 2 (genetic organs (men)). Other than this, as the target organ, "the adrenal gland" based on (1), and "the liver" based on (4) were assumed. However, findings in the adrenal glands in (1) were only observed in female rats, but not observed in dogs, and findings in the liver in (4) were considered to be adaptive changes rather than toxic ones. Moreover, there was no clear finding which suggested effects on the liver in the data of a 3-month oral administration study (OECD TG 409, GLP), (5). Therefore, these organs were excluded from the target organs. [Evidence Data] (1) In a 90-day oral (gavage) study (OECD TG 408, GLP) with male and female rats, effects on the adrenal glands (female: increased relative weight, hypertrophy of the zone fasciculata) at or above 25 mg/kg/day (within the range of Category 2) and effects on the testis and epididymis (testicular atrophy, spermatocele in the epididymis) at 50 mg/kg/day (within the range of Category 2) were observed (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018), CLP Report (2017)). [Reference Data, etc.] (2) In 14-day oral administration tests with both male rats and male mice, at 50 mg/kg/day (converted guidance value: 7.8 mg/kg/day, within the range of Category 1), testicular atrophy in rats and increased frequency in abnormal sperm in mice were observed (SCCS (2016)). (3) In a 15-day oral (gavage) test with male rabbits, at 30 mg/kg/day (converted guidance value: 5 mg/kg/day, within the range of Category 1), diffuse degeneration of the seminiferous tubules, epididymal atrophy and azoospermia (moderate in all animals) were observed in 1/5 animals, and at 100 mg/kg/day (converted guidance value: 16.7 mg/kg/day, within the range of Category 2), diffuse degeneration of the seminiferous tubules, epididymal atrophy and azoospermia (severe in all animals) were observed in 1/5 animals (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018), CLP Report (2017)). (4) In a 2-week oral (gavage) test with male dogs, at 200 mg/kg/day (converted guidance value: 30.8 mg/kg/day, within the range of Category 2), decreased body weight gain or reduced body weight with vomiting, loose stool and diarrhea, increased liver weight and centrilobular hepatocytes hypertrophy in all 4 animals, diffuse degeneration of the seminiferous tubules, hyperplasia of the Leydig cells, epithelial vacuolation and azoospermia in the epididymis in 1/4 animals were observed (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018), CLP Report (2017)). (5) In a 3-month oral dose test (OECD TG 409, GLP) with male and female dogs, no effect was observed in either the males or females at doses up to 44.6 mg/kg/day (within the range of Category 2), therefore, only for females, a 90-day administration group of 200 mg/kg/day was added, but no adverse effect was observed in females even at 200 mg/kg/day (exceeding Category 2) (SCCS (2016), NICNAS IMAP (Accessed Dec. 2018)).
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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