GHS Classification Result
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 | H28-B-049, C-086B |
| Classification year (FY) | FY2016 |
| 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 | FY2015 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 |
| 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 |
- |
- | - | From a flash point of 198 deg C (ICSC (2004)), it corresponds to "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 in contact with air at normal temperatures (autoignition temperature 425 deg C (ICSC (2004)). |
| 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. |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 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." |
| 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." |
| 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) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 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. |
| 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. |
| 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, 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 9 | Specific target organ toxicity - Repeated exposure | Category 2 (genetic organs (men)) |
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)). |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 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) (CICADs 17, 1999; Initial Risk Assessment (NITE, CERI, NEDO, 2007)), 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 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. |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data available. |
NOTE:
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* 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. |