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EC number: 201-622-7 | CAS number: 85-68-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.36 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 25
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 12.6 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
DNEL related information
Workers - Hazard for the eyes
Additional information - workers
Long-term toxicity
There is no established IOELV for BBP. The current DNEL is based on a consideration of the potential of BBP to cause long-term systemic effects, both repeated dose toxicity and reproductive (fertility, developmental) toxicity.
DNELs have been calculated both from inhalation and oral dosing.
Inhalation DNEL
Dose descriptor
A 90-day inhalation study in rats (Roloff, 1982) provides an NOAEC of 218 mg/m3(6 hours/day, 5 days/week); relative liver and kidney weights were increased at the higher test concentration of 789 mg/m3(but with no accompanying histopathological findings). The NOAEC from this study will be used to derive the DNELl-t inhalation.
Modification of dose descriptor
In line with ECHA TGD (2008) guidance, this NOAEC is corrected by adjusting for activity driven and absorption percentage differences between humans and rats.
Correct the NOAEC to adjust for differences in duration in the animal study (6 h) and the worker (8 h) and light work following the TGD Figure R.8-2:
correctedNOAEC = 218 mg/m3x [6 h / 8 h] x [6.7 m3/ 10 m3] = 109 mg/m3
It is assumed that BBP is similarly and efficiently (100%) absorbed after inhalation by rats and humans (RAR, 2007).
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
1
2.5 |
Default to account for differences in metabolic rate when doses in an inhalation study are expressed as a concentration
To account for other possible inter-species differences (mainly in pharmacodynamics) |
Intraspecies differences |
5 |
default AF for workers |
Differences in duration of exposure |
2 |
default factor for sub-chronic to chronic extrapolation |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEC, with only minor effects at the test concentration above this |
Quality of database |
1 |
default; reliable data available for all REACH required endpoints |
Overall AF |
25 |
|
DNELl-t inhal = 109 mg/m3/ 25 = 4.36 mg/m3
Oral DNELs
For comparative purposes, oral DNELs have been calculated for both repeated dose toxicity and reproductive toxicity.
Repeated dose toxicity
Dose descriptor
The NOAEL from the 14-week rat study (Ford, 1981) of 151 mg/kg bw/day will be used to derive the DNELl-t oral (repeated dose). Pancreatic lesions were evident at the next highest dose (381 mg/kg bw/day).
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
4
2.5 |
Allometric scaling factor for rat
To account for other possible interspecies differences (mainly in pharmacodynamics) |
Intraspecies differences |
5 |
default AF for workers |
Differences in duration of exposure |
2 |
default factor for subchronic to chronic extrapolation |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEL, with only mild or moderate pancreatic lesions at the LOAEL |
Quality of database |
1 |
default; reliable data available for all REACH required endpoints |
Overall AF |
100 |
|
DNELl-t oral (repeated dose) = 151 / 100 = 1.5 mg/kg bw/day
Reproductive toxicity (fertility)
Dose descriptor
The NOAEL from the 2-generation rat study (Tyl et al., 2002) of 250 mg/kg bw/day will be used to derive the DNELl-t oral (fertility). In this study, reduced mating and fertility indices were observed in the F1 generation at the next highest dose (750 mg/kg bw/day).
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
4
2.5 |
Allometric scaling factor for rat
To account for other possible interspecies differences (mainly in pharmacodynamics) |
Intraspecies differences |
5 |
default AF for workers |
Differences in duration of exposure |
1 |
duration adjustment for developmental endpoint is not appropriate; NOAEL from a 2-gen study |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEL, not an exceptional case of serious effects, good GLP study |
Quality of database |
1 |
default; reliable data available for all REACH required endpoints |
Overall AF |
50 |
|
DNELl-t oral (fertility) = 250 / 50 = 5 mg/kg bw/day
Reproductive toxicity (developmental)
Dose descriptor
The NOAEL from the 2-generation rat study (Tyl et al., 2002) of 50 mg/kg bw/day will be used to derive the DNELl-t oral (developmental). The main effect at the next highest dose of 250 mg/kg bw/day was decreased anogenital distance in male pups, an observational change occurring during their development.
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
4
2.5 |
Allometric scaling factor for rat
To account for other possible interspecies differences (mainly in pharmacodynamics) |
Intraspecies differences |
5 |
default AF for workers |
Differences in duration of exposure |
1 |
duration adjustment for developmental endpoint is not appropriate; NOAEL from a 2-gen study |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEL for an observational change with no effect on reproductive function, good GLP study |
Quality of database |
1 |
default; reliable data available for all REACH required endpoints |
Overall AF |
50 |
|
DNELl-t oral (developmental) = 50 / 50 = 1 mg/kg bw/day
Comparison of oral DNELs with inhalation DNEL
The systemic doses produced by the inhalation DNEL and by each of the oral DNELs have been calculated.
Systemic dose in humans arising from the inhalation DNEL
In an 8-hour work shift, a 70-kg man will inhale 10 m3of air. If there is 100% pulmonary absorption, the DNELl-t inhalationof 4.36 mg/m3would deliver a systemic dose of 43.6 mg of BBP (10 x 4.36 mg) or 0.62 mg/kg bw/day.
Systemic doses in humans arising from the oral DNELs
The long-term oral DNELs based on avoidance of BBP’s repeated dose toxicity and ability to interfere with fertility and development were 1.5, 5 and 1 mg/kg bw/day respectively. Assuming 70% absorption through the gastrointestinal tract, these would be associated with systemic doses of 0.7-3.5 mg/kg bw/day.
The systemic dose of 0.7 mg/kg bw/day arising from the lowest oral DNEL from the 2-generation oral rat study (Tyl et al., 2002) is higher than that of 0.62 mg/kg bw/day arising from the inhalation DNEL from the 90-day rat inhalation study (Roloff, 1982). This provides reassurance that the inhalation DNEL will be protective against the systemic reproductive toxic potential of BBP.
Dermal DNEL
In the absence of dermal toxicity studies on BBP, there are two possible studies that might be used to derive a dermal DNEL, the 90-day inhalation study of Roloff (1982) and the 2-generation oral study of Tyl et al. (2002).
1. Roloff (1982)
Dose descriptor
This rat inhalation study provides an NOAEC of 218 mg/m3(6 hours/day, 5 days/week), which needs to be modified to take account of differences in uptake between the inhalation and dermal routes of exposure (TGD, Appendix R.8-2, adaptation of Example B.4).
Modification of dose descriptor
The inhalation NOAEC in the rat (in mg/m3) is converted into a dermal NOAEL in the rat (in mg/kg bw/day) by using a default respiratory volume in the rat (sRVrat) and correcting for differences in absorption between the routes (assuming a default inhalation absorption of 100%, and 5% dermal absorption; RAR, 2007).
correctedDermal NOAEL = NOAECinhalationx sRVrat (6-h)x [ABSinhal-rat/ABSdermal-human]
= 218 x 0.288 x [100/5] = 1256 mg/kg bw/day
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
4
2.5 |
Allometric scaling factor for rat
To account for other possible interspecies differences (mainly in pharmacodynamics) |
Intraspecies differences |
5 |
default AF for workers |
Differences in duration of exposure |
2 |
default sub-chronic (90-day) to chronic |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEC with only minor effects at the test concentration above this |
Quality of database |
1 |
default; reliable data available for all REACH required endpoints |
Overall AF |
100 |
|
DNELl-t dermal = 1256 mg/kg bw/day / 100 = 12.6 mg/kg bw/day
2. Tyl et al. (2002)
Dose descriptor
This 2-generation oral rat study provides an NOAEL for developmental toxicity of 50 mg/kg bw/day, which needs to be modified to take account of differences in uptake between the oral and dermal routes of exposure (TGD, Appendix R.8-2, Example B.5).
Modification of dose descriptor
The oral NOAEL is converted into acorrecteddermal NOAEL in the rat by incorporating differences in absorption between the routes (assuming 70% absorption from the gastrointestinal tract and 5% dermal absorption; RAR, 2007).
correctedDermal NOAEL = NOAELoralx [ABSoral-rat/ABSdermal-human]
correctedDermal NOAEL = 50 x [70/5] = 700 mg/kg bw/day
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
4
2.5 |
Allometric scaling factor for rat
To account for other possible interspecies differences (mainly in pharmacodynamics) |
Intraspecies differences |
5 |
default AF for workers |
Differences in duration of exposure |
1 |
duration adjustment for developmental endpoint is not appropriate; NOAEL from a 2-gen study |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEL for an observational change with no effect on reproductive function, good GLP study |
Quality of database |
1 |
default; reliable data available for all REACH required endpoints |
Overall AF |
50 |
|
DNELl-t dermal = 700 / 50 = 14 mg/kg bw/day
Thus the Roloff 90-day inhalation study provides the lowest dermal DNEL of 12.6 mg/kg bw/day
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.78 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 50
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
DNEL related information
Local effects
Acute/short term exposure
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 200
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
DNEL related information
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.5 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
DNEL related information
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
DNEL related information
General Population - Hazard for the eyes
Additional information - General Population
Long-term toxicity
There is no established IOELV for BBP. The current DNEL is based on a consideration of the potential of BBP to cause long-term systemic effects, both repeated dose toxicity and reproductive (fertility, developmental) toxicity.
DNELs have been calculated both from inhalation and oral dosing.
Inhalation DNEL
Dose descriptor
A 90-day inhalation study in rats (Roloff, 1982) provides an NOAEC of 218 mg/m3(6 hours/day, 5 days/week); relative liver and kidney weights were increased at the higher test concentration of 789 mg/m3(but with no accompanying histopathological findings). The NOAEC from this study will be used to derive the DNELl-t inhalation.
Modification of dose descriptor
In line with ECHA TGD (2008) guidance, this NOAEC is corrected by adjusting fordifferences in duration in the animal study (6 hours/day, 5 days/week) and the general population (24 hours/day, 7 days/week) following the TGD Figure R.8-2:
correctedNOAEC = 218 mg/m3x [6 h / 24 h] x [5 day / 7 day] = 38.9 mg/m3
It is assumed that BBP is similarly and efficiently (100%) absorbed after inhalation by rats and humans (RAR, 2007).
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
1
2.5 |
Default to account for differences in metabolic rate when doses in an inhalation study are expressed as a concentration
To account for other possible interspecies differences (mainly in pharmacodynamics) |
Intraspecies differences |
10 |
default AF for general population |
Differences in duration of exposure |
2 |
default factor for subchronic to chronic extrapolation |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEC, with only minor effects at the test concentration above this |
Quality of database |
1 |
default; reliable data available for all REACH required endpoints |
Overall AF |
50 |
|
DNELl-t inhalation = 38.9 mg/m3/ 50 = 0.78 mg/m3
Oral DNELs
Oral DNELs have been calculated for both repeated dose toxicity and reproductive toxicity.
Repeated dose toxicity
Dose descriptor
The NOAEL from the 14-week rat study (Ford, 1981) of 151 mg/kg bw/day will be used to derive the DNELl-t oral (repeated dose). Pancreatic lesions were evident at the next highest dose (381 mg/kg bw/day).
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
4
2.5 |
Allometric scaling factor for rat
To account for other possible interspecies differences (mainly in pharmacodynamics) |
Intraspecies differences |
10 |
default AF for general population |
Differences in duration of exposure |
2 |
default factor for subchronic to chronic extrapolation |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEL, with only mild or moderate pancreatic lesions at the LOAEL |
Quality of database |
1 |
default; reliable data available for all REACH required endpoints |
Overall AF |
200 |
|
DNELl-t oral (repeated dose)= 151 / 200 = 0.76 mg/kg bw/day
Reproductive toxicity (fertility)
Dose descriptor
The NOAEL from the 2-generation rat study (Tyl et al., 2002) of 250 mg/kg bw/day will be used to derive the DNELl-t oral (fertility). In this study, reduced mating and fertility indices were observed in the F1 generation at the next highest dose (750 mg/kg bw/day).
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
4
2.5 |
Allometric scaling factor for rat
To account for other possible interspecies differences (mainly in pharmacodynamics) |
Intraspecies differences |
10 |
default AF for general population |
Differences in duration of exposure |
1 |
duration adjustment for developmental endpoint is not appropriate; NOAEL from a 2-gen study |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEL, not an exceptional case of serious effects, good GLP study |
Quality of database |
1 |
default; reliable data available for all REACH required endpoints |
Overall AF |
100 |
|
DNELl-t oral (fertility) = 250 / 100 = 2.5 mg/kg bw/day
Reproductive toxicity (developmental)
Dose descriptor
The NOAEL from the 2-generation rat study (Tyl et al., 2002) of 50 mg/kg bw/day will be used to derive the DNELl-t oral (developmental). The main effect at the next highest dose of 250 mg/kg bw/day was decreased anogenital distance in male pups, an observational change occurring during their development.
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
4
2.5 |
Allometric scaling factor for rat
To account for other possible interspecies differences (mainly in pharmacodynamics) |
Intraspecies differences |
10 |
default AF for general population |
Differences in duration of exposure |
1 |
duration adjustment for developmental endpoint is not appropriate; NOAEL from a 2-gen study |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEL for an observational change with no effect on reproductive function, good GLP study |
Quality of database |
1 |
default; reliable data available for all REACH required endpoints |
Overall AF |
100 |
|
DNELl-t oral (developmental) = 50 / 100 = 0.5 mg/kg bw/day
The developmental effects observed in the Tyl study provide the lowest oral DNEL of 0.5 mg/kg bw/day.
Comparison of oral DNELs with inhalation DNEL
The systemic doses produced by the inhalation DNEL and by each of the oral DNELs have been calculated.
Systemic dose in humans arising from the inhalation DNEL
In a 24-hour day, a 70-kg man will inhale 20 m3of air. If there is 100% pulmonary absorption, the DNELl-t inhalationof 0.78 mg/m3would deliver a systemic dose of 15.6 mg of BBP (20 x 0.78 mg) or 0.22 mg/kg bw/day.
Systemic doses in humans arising from the oral DNELs
The long-term oral DNELs based on avoidance of BBP’s repeated dose toxicity and ability to interfere with fertility and development were 0.76, 2.5 and 0.5 mg/kg bw/day respectively. Assuming 70% absorption through the gastrointestinal tract, these would be associated with systemic doses of 0.35-1.8 mg/kg bw/day.
The systemic dose of 0.35 mg/kg bw/day arising from the lowest oral DNEL from the 2-generation oral rat study (Tyl et al., 2002) is
higher than that of 0.22 mg/kg bw/day arising from the inhalation DNEL from the 90-day rat inhalation study (Roloff, 1982). This provides reassurance that the inhalation DNEL will be protective against the reproductive toxic potential of BBP.
Dermal DNEL
In the absence of dermal toxicity studies on BBP, there are two possible studies that might be used to derive a dermal DNEL, the 90-day inhalation study of Roloff (1982) and the 2-generation oral study of Tyl et al. (2002).
1. Roloff (1982)
Dose descriptor
This rat inhalation study provides an NOAEC of 218 mg/m3(6 hours/day, 5 days/week), which needs to be modified to take account of differences in uptake between the inhalation and dermal routes of exposure (TGD, Appendix R.8-2, adaptation of Example B.4).
Modification of dose descriptor
The inhalation NOAEC in the rat (in mg/m3) is corrected to adjust for differences in duration of exposure, then converted into a dermal NOAEL in the rat (in mg/kg bw/day) by using a default respiratory volume in the rat (sRVrat) and correcting for differences in absorption between the routes (assuming a default inhalation absorption of 100%, and 5% dermal absorption; RAR, 2007).
correctedDermal NOAEL =
NOAECinhalationx sRVrat (6 h)x [5 / 7 days] x [ABSinhal-rat/ABSdermal-human]
= 218 x 0.288 x (5/7) x (100/5) = 897 mg/kg bw/day
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
4
2.5 |
Allometric scaling factor for rat
To account for other possible interspecies differences (mainly in pharmacodynamics) |
Intraspecies differences |
10 |
default AF for general population |
Differences in duration of exposure |
2 |
default sub-chronic (90-day) to chronic |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEC with only minor effects at the test concentration above this |
Quality of database |
1 |
default; reliable data available for all REACH required endpoints |
Overall AF |
200 |
|
DNELl-t dermal = 897 mg/kg bw/day / 200 = 4.5 mg/kg bw/day
2. Tyl et al. (2002)
Dose descriptor
This 2-generation oral rat study provides an NOAEL for developmental toxicity of 50 mg/kg bw/day, which needs to be modified to take account of differences in uptake between the oral and dermal routes of exposure (TGD, Appendix R.8-2, Example B.5).
Modification of dose descriptor
The oral NOAEL is converted into acorrecteddermal NOAEL in the rat by incorporating differences in absorption between the routes (assuming 70% absorption from the gastrointestinal tract and 5% dermal absorption; RAR, 2007).
correctedDermal NOAEL = NOAELoralx [ABSoral-rat/ABSdermal-human]
correctedDermal NOAEL = 50 x [70/5] = 700 mg/kg bw/day
Assessment factors
Uncertainty |
AF |
Justificatio |
Interspecies differences |
4
2.5 |
Allometric scaling factor for rat
To account for other possible interspecies differences (mainly in pharmacodynamics) |
Intraspecies differences |
10 |
default AF for general population |
Differences in duration of exposure |
1 |
duration adjustment for developmental endpoint is not appropriate; NOAEL from a 2-gen study |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEL for an observational change with no effect on reproductive function, good GLP study |
Quality of database |
1 |
default; reliable data available for all REACH required endpoints |
Overall AF |
100 |
|
DNELl-t dermal = 700 / 100 = 7 mg/kg bw/day
Thus the 90-day rat inhalation study of Roloff, 1982 provides the lowest dermal DNEL.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.