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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
42 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance & ECETOC TR No. 110
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
DNEL value:
251 mg/m³
Explanation for the modification of the dose descriptor starting point:
No route to route is necessary since a repeated dose inhalation study is available.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for the conversion of rat NOEAC into worker NOAEC.
AF for other interspecies differences:
1
Justification:
There is no evidence for species differences in the general mode of action or kinetics.
AF for intraspecies differences:
3
Justification:
Intraspecies differences of worker are considered to be fully covered by the selected factor.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
DNEL (Derived No Effect Level)
Value:
11 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance & ECETOC TR No. 110
Overall assessment factor (AF):
9
Dose descriptor:
LOAEC
AF for dose response relationship:
3
Justification:
The assessment factor was used for extrapolation from LOAEC to NOAEC.
AF for differences in duration of exposure:
1
Justification:
Since the respiratory irritation is dependent on concentration no assessment factor for time extrapolation is used.
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
1
Justification:
There is no evidence for species differences in the general mode of action or kinetics.
AF for intraspecies differences:
3
Justification:
Intraspecies differences of worker are considered to be fully covered by the selected factor.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance & ECETOC TR No. 110
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
DNEL value:
145 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated dermal exposure.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies differences factor.
AF for other interspecies differences:
1
Justification:
There is no evidence for species differences in the general mode of action or kinetics.
AF for intraspecies differences:
3
Justification:
Intraspecies differences of worker are considered to be fully covered by the selected factor.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General

 

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA (2010) and ECETOC (2003). In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

Acute/ short-term- systemic effects

 

Short-term DNELs are not required as the acute toxicity of the test item is low. It is not classified and labelled for acute systemic toxicity, according to Directive 67/548/EEC (DSD) and Regulation EC 1272/2008 (CLP), based on the test data for acute oral, dermal and inhalation toxicity.

 

Acute/short-term and long-term exposure - local effects

 

Skin irritation/corrosion: The test item has skin irritation potential. However, no threshold data can be derived from the respective studies. A qualitative assessment is therefore used.

 

Skin sensitisation: Since the test item exhibits a skin sensitizing potential a qualitative approach is used for risk assessment.

 

Eye irritation: The test item is not classified for eye irritation based on the results of the eye irritation studies available. Therefore, no worker DNEL is derived.

 

Respiratory irritation: The acute inhalation toxicity study is not suitable to derive a dose-response relationship. Local effects on respiratory system were observed in the long-term inhalation study with the test item (BASF, 2012). Therefore, only a long term worker DNEL for local effects is derived. The LOAEL assessed in this study is identified as the relevant dose descriptor and starting point. Since the respiratory irritation is dependent on concentration no assessment factor for time extrapolation is used.

 

- Modification of the starting point

Relevant dose descriptor (LOAEL): 100 mg/m3

Assessment factor for extrapolation to NOAEC: 3

 

Corrected inhalatory NOAEC

= 100 mg/m³ / 3

= 33.3 mg/m³

 

- Calculation of the worker DNEL

Corrected inhalatory NOAEC: 33.3 mg/m³

Assessment factor for intraspecies differences (worker): 3

 

Worker DNEL (long-term inhalation exposure)

= 33.3 mg/m³ / 3

= 11 mg/m³

 

Long-term exposure – systemic effects

 

Inhalation exposure:

A worker DNEL (long-term inhalation exposure) is derived. This worker DNEL is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected). The NOAEL assessed in the key subchronic repeated dose inhalation toxicity study (BASF, 2012) is identified as the relevant dose descriptor and starting point.

 

 

- Modification of the starting point

Relevant dose descriptor (NOAEL): 500 mg/m3

Exposure duration: 6 hours/day

Exposure calculation for worker: 8 hours/day

Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³ (8h)

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³ (8h)

 

Corrected inhalatory NOAEC for workers

= 500 × (6h/d / 8h/d) × (6.7 m³ / 10 m³)

= 251 mg/m³

 

- Calculation of the worker DNEL

Corrected inhalatory NOAEC for workers: 251 mg/m³

Assessment factor for intraspecies differences (worker): 3

Exposure duration factor (subchronic-to-chronic): 2

 

Worker DNEL (long-term inhalation exposure)

= 251 mg/m³ / (3 × 2)

= 42 mg/m³

 

Dermal exposure:

In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in the key repeated dose inhalation toxicity study is identified as the relevant dose descriptor. Considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated as follows:

 

-Modification of the starting point

Relevant dose descriptor (NOAEL): 500 mg/m3

Standard respiratory volume of rats (6h): 0.29 m³/kg bw

Allometric scaling factor (rat-to-human): 4

 

Corrected dermal NOAEL for workers

= 500 mg/m3× 0.29 m3/ kg bw / 4

= 36.25 mg/kg bw/day

 

Exposure duration factor (subchronic-to-chronic): 2

Assessment factor for intraspecies differences (worker): 3

 

Worker DNEL (long-term dermal exposure)

= 36.25 mg/kg bw/day / (2 × 3)

= 6 mg/kg bw/day

 

References

(not included as endpoint study record)

 

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2. ECHA-2010 -G-19 –EN.

 

- ECETOC Technical Report No. 110 (2010). Guidance on assessment factors to derive a DNEL.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance & ECETOC TR No. 110
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
DNEL value:
125 mg/m³
Explanation for the modification of the dose descriptor starting point:
No route to route is necessary since a repeated dose inhalation study is available.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for the conversion of rat NOEAC into general population NOAEC.
AF for other interspecies differences:
1
Justification:
There is no evidence for species differences in the general mode of action or kinetics.
AF for intraspecies differences:
5
Justification:
Intraspecies differences of general population are considered to be fully covered by the selected factor.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
DNEL (Derived No Effect Level)
Value:
6.7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance & ECETOC TR No. 110
Overall assessment factor (AF):
15
Dose descriptor:
LOAEC
AF for dose response relationship:
3
Justification:
The assessment factor was used for extrapolation from LOAEC to NOAEC.
AF for differences in duration of exposure:
1
Justification:
Since the respiratory irritation is dependent on concentration no assessment factor for time extrapolation is used.
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
1
Justification:
There is no evidence for species differences in the general mode of action or kinetics.
AF for intraspecies differences:
5
Justification:
Intraspecies differences of general population are considered to be fully covered by the selected factor.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
3.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance & ECETOC TR No. 110
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
145 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated dermal exposure. The recommended approach using inhalation data assuming a two times lower absorption via the dermal route (end route) as compared to the inhalation route (starting route) is used. For details, please refer to the discussion.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies differences factor for route to route extrapolation.
AF for other interspecies differences:
1
Justification:
There is no evidence for species differences in the general mode of action or kinetics.
AF for intraspecies differences:
5
Justification:
Intraspecies differences of general population are considered to be fully covered by the selected factor.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance & ECETOC TR No. 110
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
145 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated oral exposure. The recommended approach using inhalation data assuming a two times lower absorption via the oral route (end route) as compared to the inhalation route (starting route) is used. For details, please refer to the discussion.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies differences factor for route to route extrapolation.
AF for other interspecies differences:
1
Justification:
There is no evidence for species differences in the general mode of action or kinetics.
AF for intraspecies differences:
5
Justification:
Intraspecies differences of general population are considered to be fully covered by the selected factor.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General

 

DNEL derivation for the test item is performed under consideration of the recommendations of ECETOC (2003). In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

 

Acute/ short-term- systemic effects

 

Short-term DNELs are not required as the acute toxicity of the test item is low. It is not classified and labelled for acute systemic toxicity, according to Directive 67/548/EEC (DSD) and Regulation EC 1272/2008 (CLP), based on the test data for acute oral, dermal and inhalation toxicity.

 

 

Acute/short-term and long-term exposure - local effects

 

Skin irritation/corrosion: The test item has skin irritation potential. However, no threshold data can be derived from the respective studies. A qualitative assessment is therefore used.

 

Skin sensitisation: Since the test item exhibits a skin sensitizing potential a qualitative approach is used for risk assessment.

 

Eye irritation: The test item is not classified for eye irritation based on the results of the eye irritation studies available. Therefore, no worker DNEL is derived.

 

Respiratory irritation: The acute inhalation toxicity study is not suitable to derive a dose-response relationship. Local effects on respiratory system were observed in the long-term inhalation study with the test item (BASF, 2012). Therefore, only a long term general population DNEL for local effects is derived. The LOAEL assessed in this study is identified as the relevant dose descriptor and starting point. Since the respiratory irritation is dependent on concentration no assessment factor for time extrapolation is used.

 

- Modification of the starting point

Relevant dose descriptor (LOAEL): 100 mg/m3

Assessment factor for extrapolation to NOAEC: 3

 

Corrected inhalatory NOAEC

= 100 mg/m³ / 3

= 33.3 mg/m³

 

- Calculation of the general population DNEL

Corrected inhalatory NOAEC: 33.3 mg/m³

Assessment factor for intraspecies differences (general population): 5

 

General population DNEL (long-term inhalation exposure)

= 33.3 mg/m³ / 5

= 6.7 mg/m³

 

 

Long-term exposure – systemic effects

 

Inhalation exposure:

A general population DNEL (long-term inhalation exposure) is derived and is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected). The NOAEL assessed in the key subchronic repeated dose inhalation toxicity study (BASF, 2012) is identified as the relevant dose descriptor and starting point.

 

- Modification of the starting point

Relevant dose descriptor (NOAEL): 500 mg/m3

Exposure duration: 6 hours/day

Exposure calculation for general population: 24 hours/day

 

Corrected inhalatory NOAEC for general population

= 500 × (6h/d /24h/d)

= 125 mg/m³

 

- Calculation of the worker DNEL

Corrected inhalatory NOAEC for general population: 125 mg/m³

Assessment factor for intraspecies differences (general population): 5

Exposure duration factor (subchronic-to-chronic): 2

 

General population DNEL (long-term inhalation exposure)

= 125 mg/m³ / (5 × 2)

= 12.5 mg/m³

 

Dermal exposure:

In order to derive a general population DNEL (long-term dermal exposure), the NOAEL assessed in the key repeated dose inhalation toxicity study is identified as the relevant dose descriptor. Considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated as follows:

 

-Modification of the starting point

Relevant dose descriptor (NOAEL): 500 mg/m3

Standard respiratory volume of rats (6h): 0.29 m³/kg bw

Allometric scaling factor (rat-to-human): 4

 

Corrected dermal NOAEL for general population

= 500 mg/m3× 0.29 m3/kg bw / 4

= 36.25 mg/kg bw/day

 

Exposure duration factor (subchronic-to-chronic): 2

Assessment factor for intraspecies differences (general population): 5

 

General population DNEL (long-term dermal exposure)

= 36.25 mg/kg bw/day / (2 × 5)

= 3.6 mg/kg bw/day

 

Oral exposure:

 

In order to derive a general population DNEL (long-term oral exposure), the NOAEL assessed in the key repeated dose inhalation toxicity study is identified as the relevant dose descriptor. Considering the appropriate modification and assessment factors, the worker DNEL (long-term oral exposure) is calculated as follows:

 

-Modification of the starting point

Relevant dose descriptor (NOAEL): 500 mg/m3

Standard respiratory volume of rats (6 h): 0.29 m³/kg bw

Allometric scaling factor (rat-to-human): 4

 

Corrected dermal NOAEL for workers

= 500 mg/m3× 0.29 m3/kg bw / 4

= 36.25 mg/kg bw/day

 

Exposure duration factor (subchronic-to-chronic): 2

Assessment factor for intraspecies differences (general population): 5

 

General population DNEL (long-term oral exposure)

= 36.25 mg/kg bw/day / (2 × 5)

= 3.6 mg/kg bw/day

 

 

References

(not included as endpoint study record)

 

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2. ECHA-2010 -G-19 –EN.

 

- ECETOC Technical Report 110 (2010). Guidance on assessment factors to derive a DNEL.