Latest GHS Classification Results by the Japanese Government (edited by NITE)
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 85-68-7 |
| Chemical Name | Butyl benzyl phthalate [BBP] |
| Substance ID | m-nite-85-68-7_v1 |
| Download of Excel format | Excel file |
REFERENCE INFORMATION
| Item | Information |
|---|---|
| Guidance used for the classification (External link) | To Guidance List |
| UN GHS document (External link) | To UN GHS document |
| FAQ（GHS classification results by the Japanese Government） | To FAQ |
| List of Information Sources (Excel file) | List of Information Sources |
| List of Definitions/Abbreviations | Definitions/Abbreviations |
| Sample Label by MHLW (External link) | To Workplace Safety Site (MHLW) |
| Sample SDS by MHLW (External link) | To Workplace Safety Site (MHLW) |
| OECD/eChemPortal (External link) | To OECD/eChemPortal (External link) |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
|---|---|---|---|---|---|---|---|---|
| 1 | Explosives | Not classified (Not applicable) |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 2 | Flammable gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 6 | Flammable liquids | Not classified |
- |
- | - | From a flash point of 198 deg C (ICSC (2004)), it corresponds to "Not classified." | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 7 | Flammable solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 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. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 9 | Pyrophoric liquids | Not classified |
- |
- | - | It is estimated that it does not ignite in contact with air at normal temperatures (autoignition temperature 425 deg C (ICSC (2004)). | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 10 | Pyrophoric solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Test methods applicable to liquid substances are not available. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 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). | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 13 | Oxidizing liquids | 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. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 14 | Oxidizing solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 15 | Organic peroxides | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | No data available. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 17 | Desensitized explosives | - |
- |
- | - | - | - | - |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
|---|---|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Not classified |
- |
- | - | There are 4 reported LD50 values for rats of 2,300 mg/kg (IARC 73 (1999)), 2,330 mg/kg (EU-RAR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), NTP TR 213 (1982)), 20,000 mg/kg (IARC 73 (1999)), and 20,400 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2008)). Since all of them correspond to "Not classified," it was classified as "Not classified." | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 1 | Acute toxicity (Dermal) | Not classified |
- |
- | - | There is a reported LD50 value of 6,700 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CICAD 17 (1999), EU-RAR (2008), CEPA (2000), PATTY (6th, 2012)) for rats, corresponding to "Not classified." There is a reported LD50 value of > 10,000 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), IARC 73 (1999), EU-RAR (2008), PATTY (6th, 2012)) for rabbits, corresponding to "Not classified." Based on these, it was classified as "Not classified." |
FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 1 | Acute toxicity (Inhalation: Gases) | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 1 | Acute toxicity (Inhalation: Vapours) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 2 | Skin corrosion/irritation | Not classified |
- |
- | - | Moderate irritation was observed in a skin irritation test (24-hour application) using rabbits (EU-RAR (2008)), however, in a skin irritation test using rabbits conducted later, no irritation was observed by 24-hour occlusive application to abraded and intact part (Hazard Assessment Report (CERI, NITE, 2006), EU-RAR (2008), NICNAS (2015), PATTY (6th, 2012)). In addition, as for humans, it is reported that slight irritation was observed as a result of application of a 10% solution on the skin of 15 to 30 volunteers (Hazard Assessment Report (CERI, NITE, 2006), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CEPA (2000), EU-RAR (2008), Environmental Risk Assessment for Chemical Substances vol. 2 (Ministry of the Environment, 2003)), and on the other hand, it is reported that no irritation was observed when undiluted solution of this substance was applied to the skin of 200 volunteers at a frequency of 24 hours/time, 3 times/week, for 5 weeks (Hazard Assessment Report (CERI, NITE, 2006), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CEPA (2000), EU-RAR (2008), IARC (1999), NICNAS (2015), Environmental Risk Assessment for Chemical Substances vol. 2 (Ministry of the Environment, 2003)). Furthermore, it is described in EU-RAR that from the above information, according to EU classification criteria, this substance does not need to be classified as a skin irritant (EU-RAR (2008)). Based on the above information, it was classified as "Not classified." Since new information was added to the information used for the previous classification and it was reexamined, classification was changed. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 3 | Serious eye damage/eye irritation | Not classified |
- |
- | - | It is reported that in an eye irritation test using rabbits, slight irritation was observed after 24 hours but subsided within 48 hours (Hazard Assessment Report (CERI, NITE, 2006), EU-RAR (2008), NICNAS (2015), PATTY (6th, 2012)). Furthermore, it is described in EU-RAR that from the above information, according to EU classification criteria, this substance does not need to be classified as an eye irritant (EU-RAR (2008)). Based on the above information, it was classified as "Not classified." Since new information was added to the information used for the previous classification and it was reexamined, classification was changed. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 4 | Skin sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. Besides, it is a reported that in a test where 200 volunteers were induced by 5-week repeated application of undiluted solution, and challenged by application of undiluted solution again after two weeks, it was negative (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CEPA (2000), EU-RAR (2008)). Besides, with regard to the information of a skin sensitization test using rabbits and a human patch test in volunteers which was described in the previous classification, details are unknown on confirmation of original sources, which were old papers in 1952. Therefore, they were not adopted as the evidence of the classification. |
FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 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, a mouse dominant lethal test was negative, a micronucleus assay using mouse bone marrow cell was negative, a chromosomal aberration test and a sister chromatid exchange test using mouse bone marrow cells were weakly positive (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), NICNAS (2015), IARC 73 (1999), EU-RAR (2008), CICAD 17 (1999), CEPA (2000), Environmental Risk Assessment for Chemical Substances Vol. 3 (Ministry of the Environment, 2004), PATTY (6th, 2012), NTP DB (Access on June 2016)). As for in vitro, bacterial reverse mutation tests, and mouse lymphoma assays, a chromosomal aberration test and a sister chromatid exchange test using mammalian cultured cells were all negative (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), NICNAS (2015), IARC 73 (1999), EU-RAR (2008), CICAD 17 (1999), CEPA (2000), Environmental Risk Assessment for Chemical Substances Vol. 3 (Ministry of the Environment, 2004), PATTY (6th, 2012), NTP DB (Access on June 2016)). From the above, positive was observed in in vivo chromosomal aberration test and sister chromatid exchange test, however, since the micronucleus test was negative and the dominant lethal test was also negative, and additionally, also in vitro tests were all negative, it was judged that this substance has no genotoxicity. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 6 | Carcinogenicity | Classification not possible |
- |
- | - | In carcinogenicity studies using rats or mice orally dosed (by feeding) for two years, no evidence of carcinogenicity was observed in mice, however, an increased incidence of mononuclear cell leukemia (MNCL) in females was observed for rats (NTP TR 213 (1982)). Additionally, in another test using rats orally dosed by feeding for two years, increases in incidences of pancreatic acinar cell adenoma and the same adenoma or carcinoma (combined) in males, and a slight increase in an incidence of transitional epithelial papilloma in the urinary bladder in females were observed (NTP TR 458 (1997)). However, IARC evaluated that there are inadequate evidence in humans and limited evidence in experimental animals for the carcinogenicity, and classified it in Group 3 (IARC 73 (1999)). The EU concluded as follows: the substance is a borderline case between No classification (classification not possible) and Category 3 (former DSD classification: equivalent to Category 2), however, due to the lack of genotoxic effects, no classification is proposed (EU-RAR (2008)). Additionally, NICNAS supported the views of IARC and EU and concluded that there is no sufficient evidence of human carcinogenicity of this substance from available data (NICNAS (2015)). From the above, it was classified as "Classification not possible" for this hazard class. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 7 | Reproductive toxicity | Category 1B |
 Danger |
H360 | P308+P313 P201 P202 P280 P405 P501 |
As for humans, some positive results were reported in studies on relationship between concentrations of urinary metabolites (monobutyl phthalate (MBP), monobutyl benzyl phthalate (MBzP)) of this substance (BBP) and semen parameters (semen volume, sperm count, sperm concentration, sperm motility, sperm morphology, etc.) (NICNAS (2015), Evaluation of effect for the food safety (Food Safety Commission, 2015)), however, it was described that it was doubtful due to small sample sizes, not time changes but effects at single spot, detection of other substances at the same time, etc. (NICNAS (2015)). In an earlier study by Swan et al., which examined the mother's urinary MBP, MBzP concentrations and AGI (body weight ratio of the AGD (anogenital distance)) of the sons from mother-son pairs, significant inverse correlation was found between them, however, in a study in which number of target cases of mother-son pairs was increased in the same cohort, this correlation was not observed, and this was also confirmed by other researchers (NICNAS (2015), Evaluation of effect for the food safety (Food Safety Commission, 2015)). In addition, it was pointed out that maternal urinary MBP and MBzP were associated with preterm birth, but there are reports that MBP and MBzP were not associated with preterm birth or concentrations of the maternal sex hormones (NICNAS (2015), Evaluation of effect for the food safety (Food Safety Commission, 2015)). Other than these, it is reported that there was no association between phthalate monoester levels in the breast milk and cryptorchidism, however, as a result of measurement of reproductive hormones in the serum of 96 boys with or without cryptorchidism, MBP showed positive correlations with sex hormone-binding globulin (SHBG) and LH/free testosterone ratio (a measure of Leydig cell function), and negative correlation with free testosterone, and there is a report and so on that although not significant difference, a tendency toward an increase in inhibin B (a measure of Sertoli cell function) with increasing concentration of MBzP were observed (NICNAS (2015), Evaluation of effect for the food safety (Food Safety Commission, 2015)). As above, developmental effects of this substance in humans are limited and uncertain. On the other hand, as for experimental animals, there is sufficient evidence that this substance causes testicular toxicity and reproductive impairment, and especially, the effects are significantly marked by exposure at developmental/growth period of F1. Testicular toxicity induced by BBP is characterized by decrease in testes weight, atrophy of testicular and accessory reproductive organ, and dose-dependent decreases in spermatozoal concentration. Effects of this substance on the testes and fertility were observed at the higher or the same doses as other general toxicity depending on tests, however, they are not considered secondary non-specific effects of the systemic toxicity (NICNAS (2015)). Additionally, there are sufficient reports of developmental toxicity induced by BBP, including prenatal, neonatal and postnatal endpoints. They commonly included resorptions, post-implantation loss of embryo or embryo-fetal death, fetal malformation, decreased fetal weight and birth weight. With regard to reproductive and development effects of BBP, females were less susceptible than males, in males, there were reports of reduced fetal testosterone levels, decreased male neonatal AGDs and nipple retention, delayed puberty (preputial separation), and after puberty there were decreases in testosterone, impaired sexual differentiation, and reproductive organ abnormality. These effects were observed at doses at which no significant maternal toxicity (mainly reduced body weight gain, decreased food consumption, increased liver/kidney weight) occurred (NICNAS (2015)). As above, reproductive effects in humans are uncertain, however, since reproductive and developmental effects in experimental animals are certain and noticeable in male offspring at doses at which no maternal toxicity was observed, it was classified in Category 1B. |
FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 8 | Specific target organ toxicity - Single exposure | Classification not possible |
- |
- | - | It is reported that in single dose studies using mice and rats given this substance by oral administration, at 6,000 to 9,000 mg/kg, which is above Category 2, alternating excitation and depression states occurred and paresis of the extremities, muscle tension, and loss of body weight were observed (EU-RAR (2008)). Additionally, it is reported that in rats, by a single oral administration at or near lethal dose (although not explicitly stated, because the LD50 is described as 2,000 to 20,000 mg, the dose is considered to be within the range), weight loss, apathy, and leukocytosis were observed, and at histological examination, splenitis and degeneration of the central nervous system with congestive encephalopathy, myelin degeneration, and glial proliferation were observed (CICAD 17 (1999)). From the results of these animal experiments, the effects of this substance were observed only by exposure to a large amount of this substance. Therefore, it was classified as "Classification not possible." Besides, in the previous classification, it was classified in Category 3 (respiratory tract irritation) based on description in ICSC that this substance is irritating to the eye, skin, and respiratory tract, however, ICSC is currently listed in List 3, and it was not possible to refer to the original source, therefore, the category was changed. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 9 | Specific target organ toxicity - Repeated exposure | Category 2 (reproductive organs (male)) |
Warning |
H373 | P260 P314 P501 |
For humans, there is no information with clear relevance to this substance. As for experimental animals, it is reported that in a two generation reproductive toxicity test using rats dosed by gavage, softening of the testes and a decrease in sperm in the epididymal lumina, and spermatid debris in the epididymal lumina were observed in males of F1 generation at 100 mg/kg/day, which is within the range of Category 2 (Evaluation of effect for the food safety (Food Safety Commission, 2015)). Besides, multiple repeated dose toxicity studies using rats dosed by feeding for 14 days to 106 weeks, a 3-month repeated dose toxicity study using dogs dosed by feeding, and inhalation toxicity studies using rats for 4 weeks or 13 weeks were performed, and lesions in the liver, pancreas, testes, etc. were reported at doses, which are outside the range of Category 2 (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Evaluation of effect for the food safety (Food Safety Commission, 2015)). Therefore, it was classified in Category 2 (genetic organs (men)). |
FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Classification not possible due to lack of data. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | Classification year (FY) | GHS Classification Guidance for the Japanese Government | |
|---|---|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment Short term (Acute) | Category 1 |
 Warning |
H400 | P273 P391 P501 |
From 96-hour EC50 = 0.11 mg/L for algae (Pseudokirchneriella subcapitata) (CICADs 17, 1999; Initial Risk Assessment (NITE, CERI, NEDO, 2007)), it was classified in Category 1. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 11 | Hazardous to the aquatic environment Long term (Chronic) | Category 2 |
- |
H411 | P273 P391 P501 |
Due to being rapidly degradable (a degradation rate by 2-week BOD = 80.9% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1975)), 35-day NOEC = 0.095 mg/L for fish (Oncorhynchus mykiss) (Initial Risk Assessment (NITE, CERI, NEDO, 2007)), it was classified in Category 2. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data available. | FY2016 | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
NOTE:
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