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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.075 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
DNEL value:
1.5 mg/m³
AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC. Thus, the default assessment factor for dose response relationship is 1 according to Guidance Document R.8.4.3.1 (ECHA, Nov. 2012).
AF for differences in duration of exposure:
2
Justification:
An assessment factor 2 is suggested by Guidance Document R.8 (Table R.8-5, ECHA, Nov. 2012) for exposure duration from sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
According to the Guidance Document R.8 (ECHA, Nov. 2012) allometric scaling should not be applied if the effects are not dependent on metabolic rate or systemic absorption, e.g. in the case of local effects. In case of this substance none of the available studies (acute and short term repeated dose toxicity, Irritation/Corrosion, Sensitisation) give indications of systemic bioavailability, since no systemic toxicity (or sensitisation potential) was observed. Instead, a particle-related portal of entry toxicity as toxicological mode of action is assumed. Therefore AF 1 is chosen.
AF for other interspecies differences:
1
Justification:
A factor of 2.5 is suggested by Guidance Document R.8 (ECHA, Nov. 2012) for remaining interspecies differences, but justified deviations are possible. The available sub-chronic inhalation study with the substance supports local particle-related portal of entry toxicity as toxicological mode of action. For local effects on the respiratory tract it should be taken into account that rodents like the rat are in general more sensitive compared to humans as the rat’s ventilation frequency is higher. In fact, the relevance of local portal-of-entry related effects seen in the lungs of animals for humans is currently not clear and is subject to continued scientific debate (cp. Guidance on the application of the CLP criteria, ECHA, Nov. 2012). However, it is not indicated that humans are more susceptible against these kinds of effects, therefore a factor of 1 is applied.
AF for intraspecies differences:
5
Justification:
For intraspecies variability in workers the default assessment factor is 5 according to Guidance Document R.8 (ECHA, Nov. 2012)
AF for the quality of the whole database:
1
Justification:
Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.375 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

(1) Conversion of an rat NOAECinhalatory; rep.dose from 90d rat repeated dose toxicity study into an corrected NOAECinhalatory; rep. dose (derived from figure R.8-2; Chapter R.8.4.2 of TGD "Chapter R.8: Characterisation of dose [concentration]-response for human health"):

For workers:

assumptions:

- 8 h exposure/day (long term exposure)

- Inhalation absorption rat = inhalation absorption human

corrected NOAECinhalatory; rep. dose       = rat NOAECinhalatory; rep. dose * ((6 h/d) / (8 h/d)) * (6.7 m3 (8 h) / 10 m3 (8h))

= 1.5 mg/m3 * 0.75 * 0.67

= 0.75 mg/m3

DNEL long-term for workers for inhalatory route - local effects         =    NOAEC corr. / Overall AF

                                                                                                                  =     0.75 mg/m3 / 10

=     0.075 mg/m3

(2) Derivation of a DNELshort-term extrapolated from the DNEL long-term (according to ECHA Guidance, Chapter R.8., Appendix R. 8 -8, Box 6)

For workers:

According to the German rule for OELs (Technical Rule for Hazardous Substances 900, German Federal Ministry of Labour and Social Affairs, 2006/2009) for short-term ceiling concentrations an exposure limit could be established by multiplication of an occupational exposure limit (Arbeitsplatzgrenzwert) to an exceeding factor (Überschreitungsfaktor), which is set per default 1 and could be adjusted to max 8. For the group of blocked diisocyanates an exceeding factor of 5 is applied, since no specific inhalation effects were observed in the acute inhalation studies, leading to a short term ceiling limit or a

DNELshort-term for workers for inhalatory route - local effects of 0.375 mg/m3.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.013 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Dose descriptor:
NOAEC
DNEL value:
0.15 mg/m³
AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEC. Thus, the default assessment factor is 1 according to Guidance Document R.8 (ECHA, Nov. 2012).
AF for differences in duration of exposure:
2
Justification:
An assessment factor 2 is suggested by Guidance Document R.8. (Table R.8-5, ECHA, Nov. 2012) for exposure extrapolation from subchonic to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
According to the Guidance Document R.8 (ECHA, Nov. 2012) allometric scaling should not be applied if the effects are not dependent on metabolic rate or systemic absorption, e.g. in the case of local effects. In case of this substance none of the available studies (acute and short term repeated dose toxicity, Irritation/Corrosion, Sensitisation) give indications of systemic bioavailability, since no systemic toxicity (or sensitisation potential) was observed. Instead, a particle-related portal of entry toxicity as toxicological mode of action is assumed. Therefore AF 1 is chosen.
AF for other interspecies differences:
1
Justification:
A factor of 2.5 is suggested by Guidance Document R.8 (ECHA, Nov. 2012) for remaining interspecies differences, but justified deviations are possible. The available sub-chronic inhalation study with the substance supports local particle-related portal of entry toxicity as toxicological mode of action. For local effects on the respiratory tract it should be taken into account that rodents like the rat are in general more sensitive compared to humans as the rat’s ventilation frequency is higher. In fact, the relevance of local portal-of-entry related effects seen in the lungs of animals for humans is currently not clear and is subject to continued scientific debate (cp. Guidance on the application of the CLP criteria, ECHA, Nov. 2012). However, it is not indicated that humans are more susceptible against these kinds of effects, therefore a factor of 1 is applied.
AF for intraspecies differences:
10
Justification:
For intraspecies variability in the general population the default assessment factor is 10 according to Guidance Document R.8 (ECHA, Nov. 2012).
AF for the quality of the whole database:
1
Justification:
Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov. 2012).
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.065 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The use of the test substance is restricted only to industrial applications. A direct use of this substance is not known. The exposure of consumers to this substance is unlikely to occur via consumer products, because no consumer product is known to contain this substance. Furthermore, because there is no release into the environemnt, an indirect exposure of the general population via the environment does not occur.

(1) Conversion of an rat NOAECinhalatory; rep.dosefrom 90d rat repeated dose toxicity study into an corrected NOAECinhalatory; rep. dose(derived from figure R.8-2; Chapter R.8.4.2 of TGD "Chapter R.8: Characterisation of dose [concentration]-response for human health"):

For general population:

assumptions:

- 24 h exposure/day (long term exposure)

- Inhalation absorption rat = inhalation absorption human

corrected NOAECinhalatory; rep. dose      = rat NOAECinhalatory; rep. dose* ((6 h/d) / (24 h/d)) * (5 days/week /7 days/week for the general population)

= 0.15 mg/m3* 0.25* 0.7

= 0.26 mg/m3

DNEL long-term for general population for inhalatory route - local effects        =    NOAEC corr. / Overall AF

                                                                                                                                  =     0.26 mg/m3/ 20

=    0.013 mg/m3

(2) Derivation of a DNELshort-term extrapolated from the DNEL long-term (according to ECHA Guidance, Chapter R.8., Appendix R. 8 -8, Box 6)

For general population:

According to the German rule for OELs (Technical Rule for Hazardous Substances 900, German Federal Ministry of Labour and Social Affairs, 2006/2009) for short-term ceiling concentrations an exposure limit could be established by multiplication of an occupational exposure limit (Arbeitsplatzgrenzwert) to an exceeding factor (Überschreitungsfaktor), which is set per default 1 and could be adjusted to max 5. For the group of blocked diisocyanates an exceeding factor of 5 is applied, since no specific inhalation effects or mortality were observed in the acute inhalation studies, leading to a short term ceiling limit or a

DNELshort-term for general population for inhalatory route - local effects of 0.065 mg/m3.