GHS Classification Result

日本語で表示



GENERAL INFORMATION
Item Information
CAS RN 85-68-7
Chemical Name n-Butyl benzyl phthalate
Substance ID H27-B-12-METI/M-019B_P
Classification year (FY) FY2015
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
-
-
- - Based on a flash point of 199 deg C (closed cup) (HSDB (Access on Nov 2015)), 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 425 deg C (ICSC (2005)).
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 reports of LD50 values for rats of >2,000 mg/kg (NICNAS (2015)), 2,330 mg/kg (EU-RAR (2007), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol.3 (Ministry of the Environment, 2004), IARC 73 (1999), NTP TR458 (1997), IARC 29 (1982), NTP TR213 (1982)), > 4,000 mg/kg (EU-RAR (2007)), 20,400 mg/kg (EU-RAR (2007), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), IARC 73 (1999), NTP TR458 (1997)), and 2,000-20,000 mg/kg (CEPA (2000), CICAD 17 (1999), Hazard assessment document on endocrine-disrupting action (METI, 2004)), it was classified as "Not classified."
1 Acute toxicity (Dermal) Not classified
-
-
- - Based on reports of LD50 values for rats of >2,000 mg/kg (NICNAS (2015)), and 6,700 mg/kg (PATTY (6th, 2012), EU-RAR (2007), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol.3 (Ministry of the Environment, 2004), CEPA (2000), CICAD 17 (1999), Hazard assessment document on endocrine-disrupting action (METI, 2004)), and LD50 values for rabbits of >2,000 mg/kg (NICNAS (2015)), and > 10,000 mg/kg (PATTY (6th, 2012), EU-RAR (2007), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol.3 (Ministry of the Environment, 2004), IARC 73 (1999)), 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. Besides, there is a report that after four rats inhaled saturated vapour for 6 hours (converted 4-hour equivalent value: 0.01 ppm), death was not observed (NICNAS (2015)).
1 Acute toxicity (Inhalation: Dusts and mists) Classification not possible
-
-
- - Classification not possible due to lack of data.
2 Skin corrosion/irritation Not classified
-
-
- - There is a report that in a skin irritation test with rabbits, irritation was not observed as a result of an application of the undiluted solution of this substance for 24 hours (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2007), NICNAS (2015)). In addition, there are reports that as a result of a patch test with 200 volunteers, irritation was not observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), IARC 73 (1999), EU-RAR (2007)), and as a result of an application of a 10% solution (solvent unknown) of this substance to the skin of 15-30 volunteers, mild irritation was found in 12% of the volunteers (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2007)). From the above, it was classified as "Not classified" (Category 3 in UN GHS classification). Besides, regarding the information in the previous classification, it was judged to be insufficient data for use in the classification because the test conditions were not described, and it was unknown whether it was a single application or not.
3 Serious eye damage/eye irritation Category 2B
-
Warning
H320 P305+P351+P338
P337+P313
P264
There is a report that in an eye irritation test with rabbits, as a result of an application of 0.1 mL of the undiluted solution of this substance, mild irritation was observed but this resolved after 48 hours (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2007), PATTY (6th, 2012)). From the above, it was classified in Category 2B.
4 Respiratory sensitization Classification not possible
-
-
- - Classification not possible due to lack of data.
4 Skin sensitization Classification not possible
-
-
- - Classification not possible due to lack of data. Besides, there are reports that the substance showed skin sensitization to rabbits (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)), that it did not show sensitization in a sensitization test with mice (CICAD 17 (1999)), and that patch tests in humans showed no sensitization (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2007)). All of the above data were lacking in detail and were judged to be insufficient data to determine the classification.
5 Germ cell mutagenicity Classification not possible
-
-
- - As for in vivo, it was negative in micronucleus tests with bone marrow cells of rats and mice, and a statistically significant positive result in a chromosomal aberration test with mouse bone marrow cells was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CICAD 17 (1999), IARC 73 (1999), NTP DB (Access on November 2015), Environmental Risk Assessment for Chemical Substances Vol.3 (Ministry of the Environment, 2004), CEPA (2000), EU-RAR (2007), NICNAS (2015), PATTY (6th, 2012)), but it was evaluated that responses in the chromosomal aberrations were small and indicative of only weak chromosome aberrations (CICAD 17 (1999)). As for in vitro, it was negative in a bacterial reverse mutation test, a mouse lymphoma test, a chromosomal aberration test, and a sister chromatid exchange test with mammalian cultured cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), IARC 73 (1999), CICAD 17 (1999), NTP DB (Access on November 2015), Environmental Risk Assessment for Chemical Substances Vol.3 (Ministry of the Environment, 2004), CEPA (2000), EU-RAR (2007), NICNAS (2015), PATTY (6th, 2012)). From the above, it was classified as "Classification not possible" according to the GHS classification guidance for the Japanese government.
The category of the previous classification was revised.
6 Carcinogenicity Classification not possible
-
-
- - There is no information on human carcinogenicity available for the classification. As for experimental animals, in NTP initial tests in which rats or mice were dosed by feeding (6,000 ppm (low dose), 12,000 ppm (high dose)) for 2 years, no increase in tumor development was observed in mice, but in rats, increased incidence of myelomonocytic leukemia was observed at the high dose in females (IARC 29 (1982), IARC 73 (1999), EU-RAR (2007), NICNAS (2015)). In the carcinogenicity study conducted as an additional test by NTP in which male rats and female rats were dosed at 3,000-12,000 ppm and 6,000-24,000 ppm, respectively for 2 years, pancreatic acinar-cell adenomas were observed in 10/50 cases in the high dose group of males, one of which also showed an acinar-cell carcinoma. However, in females, no significant increases in myelomonocytic leukemia and other tumors were shown, and only urinary bladder transitional-cell hyperplasia as the precancerous lesion was seen in 10/50 cases at the high dose (IARC 73 (1999), EU-RAR (2007), NICNAS (2015)). Furthermore, in an additional test with dietary restriction by NTP, the administration period was prolonged up to the maximum of 32 months, male rats and female rats were dosed by feeding at 12,000 ppm for 24 months and 24,000 ppm for 30-32 months, respectively. As a result, no increased incidence of pancreatic tumors was observed after 24 months or 30-32 months. However, in females, papillomas or carcinomas in the bladder were observed in 6/50 cases (4 of which had bladder carcinomas) after 32 months, and a significant increase in the incidence of bladder tumors (papillomas and carcinomas combined) was shown (IARC 73 (1999), EU - RAR (2007), NICNAS (2015)).
Based on the above test results in experimental animals, IARC classified this substance as "Group 3" for the carcinogenicity in 1999 stating that there was inadequate evidence in humans and limited evidence in experimental animals (IARC 73 (1999)). Before this (1993), EPA had classified it as "Group C (Possible human carcinogen)" (quoted from the carcinogen classification table in Environmental Risk Assessment for Chemical Substances Vol.3 (Ministry of the Environment, 2004)). On the other hand, the EU summarized the above animal test results and concluded that the carcinogenicity of this substance was located at the boundary between "Category 3" and "Classification not possible" as a DSD classification at the time, but by considering it was non-genotoxic, it was concluded that no need of classification was proposed (EU-RAR (2007)). Furthermore, NICNAS in Australia also supported the views of IARC and the EU and concluded that there was inadequate evidence of carcinogenicity for this substance in humans (NICNAS (2015)). Therefore, it was classified as "Classification not possible" for this hazard class.
7 Reproductive toxicity Category 1B


Danger
H360 P308+P313
P201
P202
P280
P405
P501
As for humans, it was revealed and reported that as a result of an analysis of 85 mother-son pairs, an inverse correlation was shown between the concentration of monobutyl phthalate (MBP) or monobenzyl phthalate (MBzP), which is a urinary metabolite of this substance, in the urine of mothers and the ratio of anogenital distance (AGD) to body weight (AGI: AGD/BW) (odds ratio: OR (MBP) = 10.2, OR (MBzP) = 3.8) (EU-RAR (2007), NICNAS (2015)), however, later, a follow-up study of 106 mother-son pairs revealed that MBzP in maternal urine was not associated with either AGD or AGI (NICNAS (2015)). In addition, it is reported that data related to the developmental effects of this substance in humans was restricted for use in risk assessment (NICNAS (2015)).
On the other hand, as for experimental animals, there are many reports on the reproductive and developmental toxicity of this substance, and in multiple two-generation reproduction toxicity studies with rats dosed by feeding or by gavage, roughly at doses of 400-750 mg/kg/day, a decrease in the fertility index in F0 and F1 parent animals was observed, and toxicity effects on the reproductive organs of males (decreased weight of the testis/epididymis/prostate, degeneration and atrophy of the testicular seminiferous tubules, reduction of the number of spermatozoa in the epididymis, etc.) were remarkably found (EU-RAR (2007), NICNAS (2015)). On the other hand, it was reported that in F1 and F2 pups, roughly at doses of 250-500 mg/kg/day in parent animals, in the male pups, reduction of AGD, delayed preputial separation, macroscopic and histopathological findings in the reproductive organs (decreased weight of the testes/epididymis/prostate, atrophy of the seminiferous tubules, hyperplasia of Leydig cells, a decrease in the number of epididymal sperms, etc.), also in female pups, delayed vaginal opening age in days and decreases in ovarian/uterine weight etc. were observed (EU-RAR (2007), NICNAS (2015)). In addition, there is also a report that by oral administration to pregnant rats during the organogenesis and perinatal period (gestational day 14 - lactation day 3), occurrence of malformations (such as hypospadias, undescended testes, agenesis or hypoplasia of the testis/epididymis/accessory reproductive organs, etc.) was observed in the reproductive organs of male pups (NICNAS (2015), EU-RAR (2007)). Besides, a decrease in fertility through the toxicity of this substance to male reproductive organs was also observed in the NTP test in which male rats were dosed by feeding for 10 weeks or 26 weeks and then mated with untreated females (EU-RAR (2007), NICNAS (2015)). From the above, it is clear that in experimental animals, this substance shows decreased fertility and developmental toxicity mainly in male pups. Therefore, it was classified in Category 1B for this hazard class.
Besides, the EU classified this substance as "Repr 1B" (ECHA CL Inventory (Access on November 2015)), and designated it as SVHC (Support Document for Identification of Benzyl butyl phthalate (BBP) as a Substance of Very High Concern (Adopted on 1 October 2008)).
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 is irritating to the respiratory tract in humans (Environmental Risk Assessment for Chemical Substances Vol.3 (Ministry of the Environment, 2004)). There is no data on experimental animals. From the above, it was classified in Category 3 (respiratory tract irritation).
9 Specific target organ toxicity - Repeated exposure Category 2 (testis)


Warning
H373 P260
P314
P501
There is no information on repeated exposure to this substance in humans. As for experimental animals, there are many reports of repeated administration tests with rats for 2 weeks-2 years by the oral route (mostly by feeding, partly by gavage), but in most of these, it is reported that increases in the liver and kidney weight, testicular toxicity (low values of testicular weight, testicular atrophy, a decrease in epididymal sperm count, etc.) were observed at doses exceeding Category 2 (EU-RAR (2007), NICNAS (2015)). Of these, tests with the smallest LOAEL value are a 14-day dose test with rats dosed by feeding, with a finding of an increase in the relative weight of the liver and kidney at 312 mg/kg/day (converted guidance value: 48.5 mg/kg/day (corresponding to Category 2)) (NICNAS (2015)), and a 2-year dose test with rats dosed by feeding, with a finding of an increase in the relative weight of the kidney in males at 120 mg/kg/day (EU-RAR (2007), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol 3 (Ministry of the Environment, 2004)). Although the effect in the former was observed within the range for Category 2, findings in the liver/kidneys were only increases in weights and were not accompanied by tissue changes, therefore, they were judged to be insufficient evidence for the target organ. Other than this, for the oral route, there is a 90-day feeding test report with mice or dogs (EU-RAR (2007), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)), but the findings for LOAEL were only low values of body weight, from which the target organs could not be specified. On the other hand, for the inhalation route, in the tests in which rats were exposed to this substance (estimated as vapour) by inhalation (6 hours/day, 5 days/week) for 4 weeks or 13 weeks, at 2,100 mg/m3 (converted guidance value: 0.46 mg/L/6 hr/day (equivalent to Category 2)), low values of body weight, atrophy of the spleen and testes were observed in the 4-week test, and at 789 mg/m3 (converted guidance value: 0.56 mg/L/6 hr/day (equivalent to Category 2)), an increase in the liver and kidney weight and a decrease in blood glucose level were observed in the 13-week study (EU-RAR (2007), NICNAS (2015), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)).
From the test results of the inhalation route above, the spleen and testes are considered to be the target organs, and for the oral route tests, effects on the male reproductive organs such as the testis, epididymis, and prostate at the high dose exceeding Category 2 are reported in many including reproductive toxicity tests (EU-RAR (2007), NICNAS (2015)), but there was no report on the effect on the spleen. In several test reports, changes in blood parameter values indicating anemia at high doses were reported (EU-RAR (2007), NICNAS (2015)), and it was considered that the findings in the spleen may be secondary effects from these, thus, the spleen was excluded from the target organ. Therefore, it was classified in Category 2 (testis) for this hazard class.
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
From 96-hour EC50 = 0.11 mg/L for algae (Pseudokirchneriella subcapitata) (CEPA, 2000), it was classified in Category 1.
11 Hazardous to the aquatic environment (Long-term) Category 2


-
H411 P273
P391
P501
Due to being rapidly degradable (a degradation rate by 14-day BOD = 80.9%, a degradation rate by GC = 97.9% (Official Bulletin of Ministry of International Trade and Industry, 1975)), and 28-day NOEC (lethal, reproduction, growth) = 0.075 mg/L for crustacea (Mysidopsis bahia) (CICAD 17, 1999, EU-RAR, 2007, Initial Risk Assessment (NITE, CERI, NEDO, 2007)), it was classified in Category 2.
12 Hazardous to the ozone layer Classification not possible
-
-
- - No data available.


NOTE:
* A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted.
* Hazard_statement_and/or_Precautionary_statement will show when hovering the mouse over a code of Hazard_statement_and/or_Precautionary_statement.
Hazard_statement_and/or_Precautionary_statement are also provided in the Excel file.
* Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government,
and is intended to provide a reference for preparing GHS labelling and SDS for users.
* This is a provisional English translation of classification results and is subject to revision without notice.
* The responsibility for any resulting GHS labelling and SDS referenced from this site is with users.
* Codes assigned to each of the hazard statements and codes for each of the precautionary statement are
based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations.

To GHS Information