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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.65 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
82.4 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
41.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

Based on repeated dose inhalation studies (28 -d, 90 -days, and 2 -years) in rats a lowest NOAEC of 82.4 mg/m³  for 6h per day on 5 days per week was determined in a subchronic study.

Conversion of the inhalatory rat NOAEC (starting point) into in a corrected inhalatory NOAEC (modified starting point):

- assumptions (for workers): 8h exposure/day; inhalation absorption rat = inhalation absorption human

corrected NOAEC = NOAEC, inhal * (6 h/d) / (8 h/d) * (6.7 m3 (8h) / 10 m3 (8h)) = 41.2 mg/m3 * 0.75 * 0.67 =41.4 mg/m3

AF for dose response relationship:
1
Justification:
Starting point is a NOAEC. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov 2012).
AF for differences in duration of exposure:
2
Justification:
According to ECHA Guidance on information requirements and chemical safety assessment Chapter R.8 an assessment factor of 2 for duration extrapolation sub-chronic to chronic is taken into consideration
AF for interspecies differences (allometric scaling):
1
Justification:
According to ECHA Guidance an allometric scaling factor is not applicable when setting an inhalation DNEL based on an inhalation animal study (see Appendix R.8-2 of TGD (ECHA, Nov. 2012)), therefore AF 1 is chosen.
AF for other interspecies differences:
2.5
Justification:
Default value by ECHA for all remaining systemic interspecies differences (see Table R.8-6 Default Assessment Factors of TGD (ECHA, Nov. 2012)
AF for intraspecies differences:
5
Justification:
According to ECHA Guidance an default factor for Intraspecies differences (factor 5) is chosen (see Table R.8-6 Default Assessment Factors of TGD (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).
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.25 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.65 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor:
NOAEC
Value:
41.4 mg/m³
AF for dose response relationship:
1
Justification:
Starting point is a NOAEC. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov 2012).
AF for differences in duration of exposure:
2
Justification:
According to ECHA Guidance on information requirements and chemical safety assessment Chapter R.8 an assessment factor of 2 for duration extrapolation sub-chronic to chronic is taken into consideration
AF for interspecies differences (allometric scaling):
1
Justification:
According to ECHA Guidance an allometric scaling factor is not applicable when setting an inhalation DNEL based on an inhalation animal study (see Appendix R.8-2 of TGD (ECHA, Nov. 2012)), therefore AF 1 is chosen.
AF for other interspecies differences:
2.5
Justification:
Default value by ECHA for all remaining systemic interspecies differences (see Table R.8-6 Default Assessment Factors of TGD (ECHA, Nov. 2012)
AF for intraspecies differences:
5
Justification:
According to ECHA Guidance a default factor for Intraspecies differences (factor 5, workers) is chosen.
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).
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.25 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:
DNEL (Derived No Effect Level)
Value:
0.167 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):
300
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on a repeated dose oral study in rats (NOAEL = 50 mg/kg bw/day) assuming a worst case 100% dermal absorption.

AF for dose response relationship:
1
Justification:
A standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov. 2012).
AF for differences in duration of exposure:
6
Justification:
Based on a subacute oral toxicity study a NOAEL of 50 mg/kg bw/day with the default exposure duration assessment factor of 6 (subacute-chronic) is considered.
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA TGD (see section 8.4.3.1 of TGD; ECHA, Nov. 2012) for interspecies extrapolation the default factor of 4 for metabolic differences between rat and humans is considered for both the oral and the dermal exposure route.
AF for other interspecies differences:
2.5
Justification:
A further assessment factor of 2.5 is used by default for dermal/oral exposure according to ECHA TGD (ECHA, Nov. 2012).
AF for intraspecies differences:
5
Justification:
Default safety factor accounting for intraspecies differences in susceptibility (factor 5 for workers) is assumed as described in chapter R 8.4.3.3 of TGD (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).
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.835 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.25 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):
200
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Derivation of DNEL for repeated oral exposure for general population (consumers) from NOAEL of the oral rat EOGRTS study (OECD 443) . Toxicokinetic studies with experimental animals (rats) indicated that oral absorption was complete (100%). The frequency for exposure for rats and humans via the environment is estimated to be daily. No correction for NOAEL necessary (see R 8.4.2 of TGD).

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov 2012).
AF for differences in duration of exposure:
2
Justification:
According to ECHA Guidance on information requirements and chemical safety assessment Chapter R.8 an assessment factor of 2 for duration extrapolation sub-chronic to chronic is taken into consideration.
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA TGD (see section 8.4.3.1 of TGD; ECHA, Nov. 2012) for interspecies extrapolation the default factor of 4 for metabolic differences between rat and humans is considered for both the oral and the dermal exposure route.
AF for other interspecies differences:
2.5
Justification:
A further assessment factor of 2.5 is used by default for dermal/oral exposure according to ECHA TGD (ECHA, Nov. 2012).
AF for intraspecies differences:
10
Justification:
According to ECHA Guidance a default factor for Intraspecies differences (factor 10 for general population) is chosen.
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).
AF for remaining uncertainties:
1
Justification:
No further assessment factors are considered necessary.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL extrapolated from long term DNEL

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 and professional applications. Hence there is no need to derive DNEL´s for general population (consumers).

An indirect exposure of man via the environment might occur through ingestion of foodstuff or drinking water. Therefore, a systemic oral long-term DNEL for general population is derived and will be used to assess any possible risk that could result from indirect exposure of man via the environment .