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EC number: 915-589-8 | CAS number: -
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.192 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 225
- Dose descriptor starting point:
- LOAEL
- Value:
- 35 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 43.2 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The calculation of the DNEL is based on an oral LOAEL observed in a sub-acute repeated dose oral toxicity study (OECD 422; 2014).
To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:
Corrected starting point for the inhalative route for workers:
= LOAEL(oral) * (1/0.38 m³/kg bw/day) * (ABSoral-rat/ABSinh-human) * 6.7 m³ (8h) /10 m³ (8h)* (7 days exposure rat/5 days exposure worker)
= 35 mg/kg bw/day * (1/0.38 m³/kg bw/day) * (1/2) * 0.67 m³ * 1.4 = 43.2 mg/m³
The LOAEL was corrected for interspecies difference between rat and human as well as for the differences in the experimental and human exposure conditions. The animals (rats) were exposed to the test substance 7 days/week; whereas workers are in general exposed 5 days/week (factor 7 days/5 days).
As worst case as recommended in the ECHA Guidance R.8 (2012), it is assumed that oral absorption rate is 50% of that of inhalation absorption. Thus, the corrected starting point for workers is 43.2 mg/m³ for inhalation.
- AF for dose response relationship:
- 3
- Justification:
- LOAEL/NOAEL extrapolation
- AF for differences in duration of exposure:
- 6
- Justification:
- subacute (28 d) to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- included in route to route extrapolation
- AF for other interspecies differences:
- 2.5
- Justification:
- default AF
- AF for intraspecies differences:
- 5
- Justification:
- default AF for workers
- AF for the quality of the whole database:
- 1
- Justification:
- The DNEL is based on a high-quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.54 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 900
- Dose descriptor starting point:
- LOAEL
- Value:
- 35 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEL
- Value:
- 490 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The calculation of the DNEL is based on an oral LOAEL observed in a sub-acute repeated dose oral toxicity study (OECD 422; 2014).
Route-to-Route extrapolation
For biphenyl, the parent compound of di-/tri-isopropylbiphenyl, dermal absorption was determined in an in vitro skin absorption study according to OECD test guideline 428 (Skin Absorption: In Vitro Method). In this study with human skin samples, 3.28% absorption was observed within 48 hours, corresponding to about 1 % within 8 hours (ECHA web site - Information on chemicals. - Registered substances, URL of web site: http: //echa.europa.eu/web/guest/information-on-chemicals/registered-substances).
Additional evidence on dermal absorption arises from characteristics of polyaromatic hydrocarbons: It was estimated from results of experimental in vivo and in vitro studies that less than 5 % was absorbable through human skin in vivo during 8 hours from a mixture containing among others naphthalene, methylnaphthalene as well as three- and four-ring aromatics (Creosote Council III Inc. /USA, not published). Di-/triisopropylbiphenyl is assumed to behave in a similar way as biphenyl or small polynuclear aromatics. A conservative skin absorption factor of 0.1 (10%) will be used in oral to dermal route-to-route extrapolation.
Corrected dermal LOAEL = oral LOAEL x (ABSoral rat/ABSdermal human)
= 35 mg/kg bw/day x (1/0.1)
=350 mg/kg bw/day
Corrected starting point for the dermal route for workers:
Dermal NOAEL = oral LOAEL*ABS(oral)/ABS(dermal) = 350 mg/kg bw/day *(1/1)* (7 days exposure rat/5 days exposure worker)= 490 mg/kg bw/day. It is assumed that oral and dermal absorption rates are equal.
- AF for dose response relationship:
- 3
- Justification:
- LOAEL/NOAEL extrapolation
- AF for differences in duration of exposure:
- 6
- Justification:
- subacute (28d) to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat to human allometric scaling
- AF for other interspecies differences:
- 2.5
- Justification:
- default AF
- AF for intraspecies differences:
- 5
- Justification:
- default AF for workers
- AF for the quality of the whole database:
- 1
- Justification:
- The DNEL is based on a high-quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.034 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 450
- Dose descriptor starting point:
- LOAEC
- Value:
- 35 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 15.2 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The calculation of the DNEL is based on an oral LOAEL observed in a sub-acute repeated dose oral toxicity study (OECD 422; 2014).
To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:
Corrected starting point for the inhalative route for workers:
= LOAEL(oral) * (1/1.15 m³/kg bw/day) * (ABSoral-rat/ABSinh-human)
= 35 mg/kg bw/day * (1/1.15 m³/kg bw/day) * (1/2) = 15.2 mg/m³
The LOAEL was corrected for interspecies difference between rat and human. As worst case as recommended in the ECHA Guidance R.8 (2012), it is assumed that oral absorption rate is 50% of that of inhalation absorption.
Thus, the corrected starting point for the general population is 15.2 mg/m³ for inhalation.
- AF for dose response relationship:
- 3
- Justification:
- LOAEL/NOAEL extrapolation
- AF for differences in duration of exposure:
- 6
- Justification:
- subacute (28d) to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- included in route to route extrapolation
- AF for other interspecies differences:
- 2.5
- Justification:
- default AF
- AF for intraspecies differences:
- 10
- Justification:
- default AF for the general population
- AF for the quality of the whole database:
- 1
- Justification:
- The DNEL is based on a high-quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.19 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 1 800
- Dose descriptor starting point:
- LOAEL
- Value:
- 35 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEL
- Value:
- 350 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The calculation of the DNEL is based on an oral LOAEL observed in a sub-acute repeated dose oral toxicity study (OECD 422; 2014).
Route-to-Route extrapolation
For biphenyl, the parent compound of di-/tri-isopropylbiphenyl, dermal absorption was determined in an in vitro skin absorption study according to OECD test guideline 428 (Skin Absorption: In Vitro Method). In this study with human skin samples, 3.28% absorption was observed within 48 hours, corresponding to about 1 % within 8 hours (ECHA web site - Information on chemicals. - Registered substances, URL of web site: http: //echa.europa.eu/web/guest/information-on-chemicals/registered-substances).
Additional evidence on dermal absorption arises from characteristics of polyaromatic hydrocarbons: It was estimated from results of experimental in vivo and in vitro studies that less than 5 % was absorbable through human skin in vivo during 8 hours from a mixture containing among others naphthalene, methylnaphthalene as well as three- and four-ring aromatics (Creosote Council III Inc. /USA, not published). Di-/triisopropylbiphenyl is assumed to behave in a similar way as biphenyl or small polynuclear aromatics. A conservative skin absorption factor of 0.1 (10%) will be used in oral to dermal route-to-route extrapolation.
Corrected dermal LOAEL = oral LOAEL x (ABSoral rat/ABSdermal human)
= 35 mg/kg bw/day x (1/0.1)
=350 mg/kg bw/day
Corrected starting point for the dermal route for workers:
Dermal NOAEL = oral LOAEL*ABS(oral)/ABS(dermal) = 350 mg/kg bw/day *(1/1) = 350 mg/kg bw/day. It is assumed that oral and dermal absorption rates are equal.
- AF for dose response relationship:
- 3
- Justification:
- LOAEL/NOAEL extrapolation
- AF for differences in duration of exposure:
- 6
- Justification:
- subacute (28d) to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- default
- AF for other interspecies differences:
- 2.5
- Justification:
- Default
- AF for intraspecies differences:
- 10
- Justification:
- Default
- AF for the quality of the whole database:
- 1
- Justification:
- The DNEL is based on a high-quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.02 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 1 800
- Dose descriptor starting point:
- LOAEL
- Value:
- 35 mg/kg bw/day
- Modified dose descriptor starting point:
- LOAEL
- Value:
- 35 mg/kg bw/day
- AF for dose response relationship:
- 3
- Justification:
- LOAEL/NOAEL extrapolation
- AF for differences in duration of exposure:
- 6
- Justification:
- subacute (28d) to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat to human allometric scaling
- AF for other interspecies differences:
- 2.5
- Justification:
- default AF
- AF for intraspecies differences:
- 10
- Justification:
- default AF for general population
- AF for the quality of the whole database:
- 1
- Justification:
- The DNEL is based on a high-quality study
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
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.
