NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	94-13-3
Chemical Name	Propyl 4-hydroxybenzoate
Substance ID	R02-A-062-METI, MOE
Classification year (FY)	FY2020
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 (FY2019 revised edition (Ver. 2.0))
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 classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
7	Flammable solids	Classification not possible	- -	-	-	No data available. Besides, there is information that it is combustible (GESTIS (Accessed Sep. 2020)), and a flash point was 180 deg C (test method: unknown) (GESTIS (Accessed Sep. 2020)).
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
10	Pyrophoric solids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of > 600 deg C (ECHA (Accessed Sep. 2020)).
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to solid (melting point <= 140 deg C) substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified (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 classified (Not applicable)	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
16	Corrosive to metals	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.

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] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) LD50 for rats: > 5,000 mg/kg (REACH registration dossier (Accessed Sep. 2020), NICNAS IMAP (2015)) (2) LD50 for rats (females): > 15,000 mg/kg (REACH registration dossier (Accessed Sep. 2020), NICNAS IMAP (2015))
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified."
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] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in a skin irritation test with rabbits (n = 3) (equivalent to OECD TG 404, semi-occlusive, 4-hour application, 7-day observation), no erythema or edema was seen in any animal (erythema/eschar score: 0/0/0, edema score: 0/0/0) (REACH registration dossier (Accessed Oct. 2020)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in an eye irritation test with rabbits (n = 3) (OECD TG 405, GLP, 7-day observation), slight and transient eye irritation reactions were observed but completely disappeared within 7 days (corneal opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 1/2/1.7, chemosis score: 0/0/0) (AICIS (formerly, NICNAS IMAP) (2015), REACH registration dossier (Accessed Oct. 2020)). [Reference Data, etc.] (2) It is reported that in an in-vitro eye irritation test (OECD TG 437, GLP), in vitro irritation score (IVIS) = 13.03 (corresponding to "no prediction can be made") (AICIS (formerly, NICNAS IMAP) (2015), REACH registration dossier (Accessed Oct. 2020)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) It is reported that in a maximization test with guinea pigs (the number of animals: unknown) (OECD TG 406, intradermal administration: 0.5% solution), a positive rate was 0% at both 24, 48 hours after a challenge (REACH registration dossier (Accessed Oct. 2020)). (2) It is reported that in a local lymph node assay (LLNA) with mice (n = 4/group) (OECD TG 429), stimulation index (SI values) was 1.3 (5%), 1.6 (10%), 1.3 (25%) in the first laboratory, 1.9 (5%), 2.2 (10%), 1.3 (25%) in the second laboratory, 1.0 (5%), 1.2 (10%), 1.5 (25%) in the third laboratory, and 1.2 (5%), 0.5 (10%), 2.0 (25%) in the fourth laboratory (REACH registration dossier (Accessed Oct. 2020)). (3) It is reported that in a local lymph node assay (LLNA) with mice (n = 4/group) (OECD TG 429), stimulation index (SI values) was 1.4 (5%), 1 (10%), 1.3 (25%) (REACH registration dossier (Accessed Oct. 2020)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) In a bacterial reverse mutation test, negative results were reported (REACH registration dossier (Accessed Sep. 2020), NICNAS IMAP (2015)). (2) In a gene mutation test using Chinese hamster lung fibroblasts, negative results were reported (REACH registration dossier (Accessed Sep. 2020), NICNAS IMAP (2015)). (3) In a chromosomal aberration test using human lymphocytes, negative results were reported (REACH registration dossier (Accessed Sep. 2020)). [Reference Data, etc.] (4) In a chromosomal aberration test using the bone marrow cells from mice, negative results were reported (Int. J. Toxiciol. (2008)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification was not possible due to lack of data. [Reference Data] (1) Concerns have been raised that parabens may induce cancer growth in humans. These concerns may arise from the detection of parabens in breast cancer tissues and the finding that parabens exhibited weak estrogenic activities. However, no study had demonstrated a causal relationship between paraben exposure and carcinogenesis (NICNAS IMAP (2015)). (2) Female mice were orally dosed with this substance (unknown dosage) 3 times every other day for 5 days from days 15 to 19 of gestation. Naturally delivered neonate mice were sacrificed after one year, and no tumor formation was observed. On the other hand, neonates were given subcutaneous administration of this substance at a total amount equivalent to LD20 on postnatal days 1, 8, 15 and 22 and sacrificed one year after birth, and no tumor formation was observed (Int. J. Toxicol, 27 (Suppl. 4), 1-82 (2008), REACH registration dossier (Accessed Sep. 2020)). (3) This substance was not genotoxic in vitro and in vivo tests. There were studies available, investigating hyperplasia of the forestomach in rats and hamsters after the administration of this substance via diet for 8 and 20 weeks, respectively. The result with rats was negative and the result with hamsters was positive. However, in other toxicity studies with rats and dogs, no evidence for preneoplastic and neoplastic lesions was observed. Based on the above results, this substance was considered to have no carcinogenic potential (REACH registration dossier (Accessed Sep. 2020)). (4) Ethyl- and propylparaben (this substance) did not show any significant genotoxic effects in in vitro and in vivo genotoxicity tests. From the available in vivo carcinogenicity studies on methyl-, ethyl- and propylparaben, it was concluded that they were not considered to be carcinogenic (RIVM (2018)).
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) It was reported that in an extended one-generation reproductive toxicity study with rats dosed by gavage (OECD TG443, GLP, for 10 weeks or more, i.e. during 2 weeks before mating, the maximum weeks of mating period, and until necropsy (P males); from 2 weeks before mating until day 21 of lactation (P females); from the day of weaning until the day before necropsy (F1)), no effect on reproductive functions in parental animals and no effect on development and growth until weaning in pups (cohort 1A) was observed at doses of up to 1,000 mg/kg/day. The administration to the pups was started, in the same way as the parental animals, after weaning of the cohort 1A, but no effect on the reproductive functions of the grown pups was observed. It was also reported that the administration to cohort 1B was started at doses of up to 1,000 mg/kg/day in the same way after weaning, but neither effect on reproductive functions or fertility of the grown pups nor effect on development of F2 was observed (REACH registration dossier (Accessed Sep. 2020)). (2) It was reported that in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with rats by feeding (OECD TG422, GLP, 28 days (males), from 14 days before mating until day 4 post partum (females)), no reproductive toxicity was observed (NICNAS IMAP (2015), REACH registration dossier (Accessed Sep. 2020), RIVM (2018)). (3) It was reported that in a reproduction/developmental toxicity screening test with rats dosed by gavage (35 days or more including 21 days of pre-mating and maximum of 14 days of mating (males), from 21 days before mating until day 21 of lactation (females)), no reproductive toxicity was observed (REACH registration dossier (Accessed Sep. 2020)). (4) It was reported that in a developmental toxicity study with rats dosed by gavage (OECD TG414, GLP, days 5 to 19 of gestation), no developmental toxicity was observed (REACH registration dossier (Accessed Sep. 2020)).
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified" in the oral route. However, classification was not possible due to lack of data since there was not sufficient information available for classification in other routes. [Evidence Data] (1) It was reported that in an acute oral toxicity test with rats, neither death nor symptom was observed at 5,000 mg/kg (in the range corresponding to "Not classified") (REACH registration dossier (Accessed Sep. 2020), NICNAS IMAP (2015)). (2) It was reported that in an acute oral toxicity test with rats, neither death nor symptom was observed at 15,000 mg/kg (in the range corresponding to "Not classified") (REACH registration dossier (Accessed Sep. 2020), NICNAS IMAP (2015)).
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1), effects on the liver and testes were observed within the range for Category 2, but no effect was observed in the longer-term tests of (2) to (5). Therefore, they were not adopted as the target organs. In addition, it was classified as "Not classified" in the oral route. However, classification was not possible due to lack of data since there was not sufficient information available for classification in other routes. [Evidence Data] (1) It was reported that in a 4-week oral toxicity study with rats, at 100 mg/kg/day (converted guidance value: 31.1 mg/kg/day, within the range for Category 2), liver effects (an increase in relative weight, dilated congested central and portal veins, focal areas of dilated sinusoids, proliferated bile ducts with fibrosis, expanded portal areas with edema, multifocal areas of necrotic hepatocytes with inflammatory cells infiltration, severe cytoplasmic vacuolization of hepatocytes), increases in serum ALT, AST, ALP and LDH activities, testis effects (such as spermatogenic arrest, seminiferous tubules occupied with eosinophilic structure and giant cells in the lumen, detached spermatogenic lineage, edematous eosinophilic interstitial space with congested blood vessels, and a mild loss of Leydig cells population), increases in lipid peroxidation and NO generation, decreases in serum testosterone (T) and T/E2 ratios, and an increase in serum E2 were observed (CIR Expert Panel Report (2019)). (2) It was reported that in an oral toxicity study with rats dosed by feeding (OECD TG422, males: for 28 days, females: from 14 days before mating until day 4 post partum), no effect was observed at 15,000 ppm (minimum value: 605 to 1,074 mg/kg/day, converted guidance value (males): 188 to 334 mg/kg/day, in the range corresponding to "Not classified") (NICNAS IMAP (2015)). (3) It was reported that in a 90-day oral toxicity study with rats dosed by gavage (OECD TG408, GLP, 7 days/week), no effect was observed at the highest dose of 1,000 mg/kg/day (in the range corresponding to "Not classified") (REACH registration dossier (Accessed Sep. 2020)). (4) It was reported that in a 96-week oral toxicity study with rats dosed by feeding, reduced body weight gain was observed at the high dose of 80,000 ppm (5,500 to 5,900 mg/kg/day, in the range corresponding to "Not classified") and the NOAEL was 20,000 ppm (900 to 1,200 mg/kg/day) (NICNAS IMAP (2015)). (5) It was reported that in an oral toxicity study with dogs dosed by gavage (oral dose by capsules for the maximum of 394 days, 6 days/week), no effect was observed at 1,000 mg/kg/day (857 mg/kg/day, in the range corresponding to "Not classified") (REACH registration dossier (Accessed Sep. 2020)). [Reference Data, etc.] (6) It was found that urinary paraben concentrations were associated with urinary glucose levels in women in the high-risk population of gestational diabetes mellitus (GDM), but a causal relationship has not been established. In one study, a positive association between the concentrations of this substance in urine and urinary glucose levels was observed among overweight/obese pregnant women, but not in the overall population. It is also important to note that other studies reported no corellation, or suggested a negative corellation, between urinary propylparaben concentrations and GDM (CIR Expert Panel Report (2019)).
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 Short term (Acute)	Category 2	- -	H401	P273 P501	It was classified in Category 2 from 96-hour LC50 = 6.4 mg/L for fish (Danio rerio) (REACH registration dossier, 2021).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	Sufficient data on rapid degradability were not obtained. If chronic toxicity data are used, then it is classified in Category 2 from 21-day NOEC = 0.25 mg/L for crustacea (Daphnia magna) (REACH registration dossier, 2021). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 2 from 96-hour LC50 = 6.4 mg/L for fish (Danio rerio) (REACH registration dossier, 2021). From the above results, it was classified in Category 2.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.

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.

To GHS Information