Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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