GHS Classification Result

日本語で表示



GENERAL INFORMATION
Item Information
CAS RN 117-81-7
Chemical Name Bis(2-ethylhexyl) phthalate
Substance ID H26-B-081, R-062
Classification year (FY) FY2014
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 FY2007   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)
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
-
-
- - It was classified as "Not classified" based on a flash point of 195 deg C (closed cup) (GESTIS (Access on September 2014)).
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 350 deg C (ICSC (2001)).
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
-
-
- - Based on multiple reports of an LD50 value of > 20,000 mg/kg (NICNAS (2010), DFGOT vol. 25 (2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EU-RAR (2003), ATSDR (2002), Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002), IARC 77 (2000), ACGIH (7th, 2001), OEL Documentations (Japan Society For Occupational Health (JSOH), 1995), CEPA (1994), EHC 131 (1992), NTP TR217 (1982)) for rats, it was classified as "Not classified."
1 Acute toxicity (Dermal) Not classified
-
-
- - Based on a report of an LD50 value of 25,000 mg/kg (> 19,600 mg/kg (> 20 mL/kg)) (PATTY (6th, 2012), NICNAS (2010), DFGOT vol. 25 (2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EU-RAR (2003), ATSDR (2002), ACGIH (7th, 2001), OEL Documentations (Japan Society For Occupational Health (JSOH), 1995), EHC 131 (1992)) for rabbits, it was classified as "Not classified."
1 Acute toxicity (Inhalation: Gases) Not applicable
-
-
- - Liquid (GHS definition)
1 Acute toxicity (Inhalation: Vapours) Classification not possible
-
-
- - Classification not possible due to lack of data.
1 Acute toxicity (Inhalation: Dusts and mists) Not classified
-
-
- - Based on a report of an LC50 value (4 hours) of > 10.62 mg/L (NICNAS (2010), DFGOT vol. 25 (2009), EU-RAR (2003)) for rats, it was classified as "Not classified." Besides, since the LC50 value was higher than the saturated vapor concentration (0.16 mg/L), a reference value as a mist was applied.
2 Skin corrosion/irritation Not classified
-
-
- - There are 2 reports of skin irritation tests (OECD TG 404) with rabbits. In one study, neither erythema nor edema was observed, and the irritation score was 0 (EU-RAR (2003)). In the other study, although slight erythema (3/3 animals) at 1 hour after application, significant erythema (1/3 animals) at 24 hours after application, and slight erythema (3/3 of the animals) at 48 hours after application were observed, they resolved 8 days after application, therefore, it was judged to be slightly irritating (EU-RAR (2003)). In addition, in another skin irritation test with rabbits (FDA recommended method, GLP-compliant), after 24-hour application of this substance, slight to moderate skin reaction was observed but this disappeared after 48 hours, therefore, it was judged to be slightly irritating (EU-RAR (2003)). Moreover, there is a report that in humans, the undiluted liquid of this substance was applied occlusively to the backs of 23 subjects for 7 days and reapplied on the 10th day, and no skin reaction was observed (EU-RAR (2003)). From the above results, it was classified as "Not classified" (Category 3 in UN GHS classification). The category was changed according to the revised GHS classification guidance for the Japanese government.
3 Serious eye damage/eye irritation Category 2B
-
Warning
H320 P305+P351+P338
P337+P313
P264
There are 2 results of eye irritation tests (OECD TG 405) in which 0.1 mL of the undiluted liquid of this substance was applied to rabbits. In one test, the average scores for the conjunctival redness, and corneal opacity and conjunctiva swelling were 0.1, 0 and 0, respectively (EU-RAR (2003)). In the other test, although slight conjunctival redness (3/3 animals) and slight ocular discharge (1/3 animals) were observed 1 hour after application, they resolved 24 hours after application (EU-RAR (2003)). In addition, in another eye irritation test (FDA recommended method, GLP-compliant) with rabbits, after application of 0.1 mL of the undiluted liquid of this substance, although slight conjunctival redness was observed 1 and 24 hours after application, they resolved 72 hours after application (EU-RAR (2003)). From the above results, it was classified in Category 2B.
4 Respiratory sensitization Classification not possible
-
-
- - Classification not possible due to lack of data.
4 Skin sensitization Not classified
-
-
- - There are 2 reports of sensitization tests (Maximization method, Buehler method) with guinea pigs. In the Maximization test, no positive reaction of skin erythema was observed, and no skin sensitization was shown (EU-RAR (2003)). In the Buehler method, in all guinea pigs including the control group, no skin reaction was observed and no sensitization was shown (EU-RAR (2003)). Besides, there is a report that in humans, the undiluted liquid of this substance was applied occlusively to the backs of 23 subjects for 7 days and reapplied on the 10th day, and no skin reaction was observed (EU-RAR (2003)). From the above results, it was classified as "Not classified."
5 Germ cell mutagenicity Classification not possible
-
-
- - The substance was classified as "Classification not possible" because it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese government. As for in vivo, in gene mutation tests with rats and mice, a mouse dominant lethal test, micronucleus tests with bone marrow cells and peripheral blood of mice, a micronucleus test with rat bone marrow cells, chromosomal aberration tests with rats and hamsters, and DNA damage tests with liver of rats and mice, although many of them were negative, positive results were also observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EU-RAR (2008), IARC 101 (2013), NTP DB (Access on September 2014), ATSDR (2002), DFGOT vol. 25 (2009), PATTY (6th, 2012)). Also in vitro, in bacterial reverse mutation tests, mammalian cell gene mutation tests, chromosomal aberration tests, sister chromatid exchange tests, a DNA damage test, and an unscheduled DNA synthesis test, there were many negative results but also few positive results (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), NTP DB (Access on September 2014), ATSDR (2002), DFGOT vol. 25 (2009), EU-RAR (2008)). It is described in EU-RAR (2008) and NICNAS (2010) that although there were positive results both in vivo and in vitro, the majority of the test systems for detection of gene mutations, chromosomal aberrations and DNA damage were negative. Therefore, this substance was not mutagenic.
6 Carcinogenicity Category 2


Warning
H351 P308+P313
P201
P202
P280
P405
P501
It was classified in 2B by IARC (2013), in A3 by ACGIH (2001), in Group 2B by Japan Society For Occupational Health (JSOH, 1991), in B2 by EPA (1988), and as R by NTP (2001). From these classifications, the EPA's classification corresponds to Category 1B, and those by the other organizations correspond to Category 2. Since the classification by IARC, the evaluation year of which is new, was prioritized, it was classified in Category 2.
Besides, IARC continuously collected information on the mechanism of hepatocarcinogenicity as to this substance and PPAR agonists, and it is described in IARC that since the findings, which suggest that the mechanisms of tumorigenesis in the liver (hepatocellular adenomas/carcinomas) and testis (Leydig-cell tumours) may involve multiple mechanisms (mechanism in which the activation of liver Kupffer cells by oxidative stress causes DNA damage, mechanism through nuclear receptors (CAR, PXR, etc.) other than PPAR and so on) in addition to those mediated by PPAR alpha, were obtained, proliferative changes in the liver and testes cannot be explained solely by the hypothesis that they are rodent-specific mechanisms of toxicity by PPAR, therefore, in 2011, IARC changed the classification of the carcinogenicity of this substance again from Group 3 (IARC vol. 77 (2000)) to Group 2B (IARC (2011), IARC vol. 101 (2013)).
7 Reproductive toxicity Category 1B, Additional category: Effects on or via lactation


Danger
H360 P308+P313
P201
P202
P280
P405
P501
In a continuous breeding test with mice by the oral route (feeding), although the dose where parental toxicity was observed was not clear, decreased pregnancy rate, decreases in litter size and the number of live pups were observed, and effects on the fertility of both sexes were identified in crossbreeding. In a three-generation reproductive toxicity study with rats by the oral route (feeding), testicular toxicity was observed and effects on fertility were observed at higher doses than doses where testicular toxicity was observed (EU-RAR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)).
In a teratogenicity test with mice by the oral route (gavage), fetotoxicity (increased fetal resorptions, fetal death, increased external and visceral malformations) was observed at doses where no maternal toxicity was observed. In a study in which female rats were exposed by the oral route (drinking water) during the gestational period and lactation period, pups toxicity (degeneration of the seminiferous tubule epithelium of the testes, shrinkage of the renal glomeruli with signs of glomerulonephritis of the kidney) was observed at doses where no maternal toxicity was observed (EU-RAR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)).
From the above, it was classified in Category 1B. In addition, since pups toxicity was observed by administration to maternal animals during the gestational and lactation period, it was classified as "Additional category: Effects on or via lactation."
Besides, this substance was classified in reproductive toxicants Group 1 in Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2014), and it corresponds to Category 1A. However, the classification of Recommendation of Occupational Exposure Limits was not adopted because it is in the provisional period.
8 Specific target organ toxicity - Single exposure Category 3 (Respiratory tract irritation)


Warning
H335 P304+P340
P403+P233
P261
P271
P312
P405
P501
This substance was irritating to the respiratory tract (Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002), ACGIH (7th, 2001), HSDB (Access on August 2014)). Although many cases were reported in humans, few could be judged as acute toxic symptoms due to this substance alone. Abdominal pain and diarrhea were reported by the ingestion of large amounts (Environmental Risk Assessment for Chemical Substances Vol.1 (Ministry of the Environment, 2002), ACGIH (7th, 2001), HSDB (Access on August 2014), ATSDR (2002), DFGOT vol. 25 (2009), EHC 131 (1992), EU-RAR (2008), NICNAS (2010)). From the above, it was classified in Category 3 (respiratory tract irritation).
9 Specific target organ toxicity - Repeated exposure Category 2 (liver, testis)


Warning
H373 P260
P314
P501
Since in tests with rats dosed by feeding for 13 weeks or 2 years, both effects on the testes (vacuolation of the Sertoli cells, bilateral complete loss of spermatogenesis) and effects on the liver (increased weight, hepatocellular hypertrophy) were observed within the range of Category 2 (testis: 28.9-37.6 mg/kg/day, liver: 37-63 mg/kg/day) (ATSDR (2002), EU-RAR (2008)), it was classified in Category 2 (liver, testis). Although the liver and testis are carcinogenic target organs of this substance, and it was considered in the past that the mechanism of tumorigenesis was related to PPAR alpha and was different between species, recently, several other mechanisms were assumed, and the carcinogenicity mentioned above was no longer considered to be by the rodent-specific mechanism of toxicity (IARC vol. 101 (2013)). The previous GHS classification (GHS classification results (Ministry of Economy, Trade and Industry FY2007 project, revised GHS classification by MHLW, METI and MOE based on reviewing public comments), published in March 2008) supported the conventional hypothesis that the toxicity observed in the liver, testes, etc. after repeated administration to rats and mice does not occur in humans, and the classification was changed from "Classification not possible" to "Not classified" for this hazard class. However, at this time, it was further changed to Category 2 reflecting recent findings.
10 Aspiration hazard Classification not possible
-
-
- - 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) Category 1


Warning
H400 P273
P391
P501
It was classified in Category 1 from 48-hour EC50 = 0.133 mg/L for crustacea (Daphnia pulex) (Environmental Risk Assessment for Chemical Substances Vol. 1 (Ministry of the Environment, 2002), Initial Risk Assessment (NITE, CERI, NEDO, 2005)).
11 Hazardous to the aquatic environment (Long-term) Category 2


-
H411 P273
P391
P501
It was classified in Category 2 due to rapid degradability (a 28-day degradation rate by BOD = 69% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1975)), and 21-day NOEC = 0.077 mg/L for crustacea (Daphnia magna) (Environmental Risk Assessment for Chemical Substances Vol. 1 (Ministry of the Environment, 2002)).
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.

To GHS Information