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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:
58.96 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):
12.5
Dose descriptor starting point:
NOAEL
Value:
286 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
737 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. A conservative approach is used assuming a two times higher absorption via the inhalation route (end route) as compared to the oral route (starting route). For details, please refer to the "additional information-worker".

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:
1
Justification:
No time extrapolation factor is needed since a chronic toxicity study is available.
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
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
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.3 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):
17.5
Dose descriptor starting point:
NOAEL
Value:
286 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
286 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. A conservative approach is used assuming identical dermal and oral absorption values. For details, please refer to the "additional information-worker".

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:
1
Justification:
No time extrapolation factor is needed since a chronic toxicity study is available.
AF for interspecies differences (allometric scaling):
1.4
Justification:
The default allometric scaling factor for the differences between dogs and humans is used.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
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
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Acute, systemic DNEL

Short term DNELs are not required as the acute toxicity of the test substance is low. The test substance is not classified and labelled for acute systemic toxicity, according to Regulation 1272/2008/EC (CLP), based on the test data for acute oral, dermal and inhalative toxicity.

 

Acute/longterm, local

The test substance is not classified and labelled as irritating to skin. Furthermore it is not considered as sensitising based on several Buehler assays in guinea pigs. The test substance is considered as eye damaging. Therefore respective qualitative risk minimisation measures need to be taken into account for the risk assessment.

 

Long term, systemic DNEL

Occupational exposure to the test substance occurs mainly by dermal route, and may also occur by inhalation exposure. Therefore two long-term DNELs are calculated for workers. In view of the data used for evaluation, the "quality of whole database factor" and "dose-response factor" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

Exposure by inhalation

 

Step 1: Selection of the relevant dose descriptor (starting point):

In order to derive a long-term inhalation DNEL, an inhalation NO(A)EC was derived from NO(A)EL oral value (determined in a 1-year repeated dose toxicity study with dogs), as no repeated dose inhalation study was available. Oral NO(A)EL of 286 mg/kg bw/day was converted to an inhalation NO(A)EC, assuming 100 % absorption via the lung and 50 % absorption via the oral route.

 

Step 2: Modification into a correct starting point:

The oral NO(A)EL was converted into an inhalation NO(A)EC according to the following formula assuming a daily exposure period of 8 hours during light activity:

 

Relevant dose descriptor (NO(A)EL): 286 mg/kg bw/day

Standard respiratory volume of the dog (sRVdog) for 8 hours: 0.13 m³/kg bw/day

Oral absorption of the dog / inhalation absorption of humans (ABSoral-dog / ABSinh-human): 0.5

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

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

 

Corrected inhalatory NOAEC for workers

= 286 mg/kg bw/day × (1 / 0.13 m³/kg bw/day) × 0.5 × (6.7 m³/10 m³)

= 737 mg/m³

 

Step 3: Use of assessment factors: 12.5

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 1

 

In conclusion, long term systemic inhalation DNEL, workers = 59 mg/m³

 

Dermal exposure

 

Step 1: Selection of the relevant dose descriptor (starting point):

In order to derive a long-term dermal DNEL, a dermal NO(A)EL was derived from NO(A)EL oral value (determined in a 1-year repeated dose toxicity study with dogs), as no repeated dose dermal study was available. The oral NO(A)EL of 286 mg/kg bw/day was used as starting point.

 

Step 2: Modification into a correct starting point:

Correction for dermal absorption rates of the test substance (based on Guidance on information requirements and chemical safety assessment, R. 7C, 2014, Chapter R 7.12):

Dermal absorption is supposed to be favourable regarding the molecular weight of 261.3 g/mol. Therefore, oral NO(A)EL of 286 mg/kg bw/day was converted to a dermal NO(A)EL, considering a comparable absorption via dermal and oral route.

 In conclusion, dermal NO(A)EL = 286 mg/kg bw/d.

 

Step 3: Use of assessment factors: 17.5

Interspecies AF, allometric scaling (dog to human): 1.4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 1

 

In conclusion, long term systemic dermal DNEL, workers = 16.3 mg/kg bw/day.

 

References

(not included as endpoint study record)

 

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health.

 

- ECHA (2014). Guidance on information requirements and chemical safety assessment. Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.4 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):
25
Dose descriptor starting point:
NOAEL
Value:
286 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
298 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. A conservative approach is used assuming a two times higher absorption via the inhalation route (end route) as compared to the oral route (starting route).

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:
1
Justification:
No time extrapolation factor is needed since a chronic toxicity study is available.
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
10
Justification:
The default value for the more heterogenous group "general population" is used.
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
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:
8.2 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):
35
Dose descriptor starting point:
NOAEL
Value:
286 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
286 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. A conservative approach is used assuming identical dermal and oral absorption values. For details, please refer to the "additional information-general population".

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:
1
Justification:
No time extrapolation factor is needed since a chronic toxicity study is available.
AF for interspecies differences (allometric scaling):
1.4
Justification:
The default allometric scaling factor for the differences between dogs and humans is used.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
10
Justification:
The default value for the more heterogenous group "general population" is used.
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
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:
8.2 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):
35
Dose descriptor starting point:
NOAEL
Value:
286 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation is necessary since a repeated dose oral toxicity 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:
1
Justification:
No time extrapolation factor is needed since a chronic toxicity study is available.
AF for interspecies differences (allometric scaling):
1.4
Justification:
The default allometric scaling factor for the differences between dogs and humans is used.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
10
Justification:
The default value for the more heterogenous group "general population" is used.
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
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Acute, systemic DNEL

Short term DNELs are not required as the acute toxicity of the test substance is low. The test substance is not classified and labelled for acute systemic toxicity, according Regulation 1272/2008/EC (CLP), based on the test data for acute oral, dermal and inhalative toxicity.

 

Acute/longterm, local

The test substance is not classified and labelled as irritating to skin. Furthermore it is not considered as sensitising based on several Buehler assays in guinea pigs. The test substance is considered as eye damaging. Therefore respective qualitative risk minimisation measures need to be taken into account for the risk assessment.

 

Long term, systemic DNEL

Three long-term DNELs are calculated for consumers. In view of the data used for evaluation, the "quality of whole database factor" and "dose-response factor" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

Exposure by inhalation

 

Step 1: Selection of the relevant dose descriptor (starting point):

In order to derive a long-term inhalation DNEL, an inhalation NO(A)EC was derived from NO(A)EL oral value (determined in 1-year repeated dose toxicity study with dogs), as no repeated dose inhalation study was available. Oral NO(A)EL of 286 mg/kg bw/day was converted to an inhalation NO(A)EC, assuming 100 % absorption via the lung and 50 % absorption via the oral route.

 

Step 2: Modification into a correct starting point:

Relevant dose descriptor (NO(A)EL): 286 mg/kg bw/day

Standard respiratory volume of the dog (sRVdog) for 24 hours: 0.48 m³/kg bw/day

Oral absorption of the dog / inhalation absorption of humans (ABSoral-dog / ABSinh-human): 0.5

 

Corrected inhalatory NOAEC for general population

= 286 mg/kg bw/day × (1 / 0.48 m³/kg bw/day) × 0.5

= 298 mg/m³

 

Step 3: Use of assessment factors: 25

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 1

 

In conclusion, long term systemic inhalation DNEL, general population = 11.9 mg/m³

 

Dermal exposure

 

Step 1: Selection of the relevant dose descriptor (starting point):

In order to derive a long-term dermal DNEL, a dermal NO(A)EL was derived from NO(A)EL oral value (determined in a 1 -year repeated dose toxicity study with dogs), as no repeated dose dermal study was available. The oral NOAEL of 286 mg/kg bw/day was used as starting point.

 

Step 2: Modification into a correct starting point:

Correction for dermal absorption rates of the test substance (based on Guidance on information requirements and chemical safety assessment, R. 7C, 2014, Chapter R 7.12):

Dermal absorption is supposed to be favourable regarding the molecular weight of 261.3 g/mol. Therefore, oral NO(A)EL of 286 mg/kg bw/day was converted to a dermal NO(A)EL, considering a comparable absorption via dermal and oral route.

In conclusion, dermal NO(A)EL = 286 mg/kg bw/d.

 

Step 3: Use of assessment factors: 35

Interspecies AF, allometric scaling (dog to human): 1.4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 1

 

In conclusion, long term systemic dermal DNEL, general population = 8.2 mg/kg bw/day.

 

Oral exposure

 

Step 1: Selection of the relevant dose descriptor (starting point):

In order to derive a long-term oral DNEL, the NOAEL determined in the 1-year repeated dose toxicity study with dogs was identified as the relevant dose descriptor (286.5 mg/kg bw/day).

 

Step 2: Use of assessment factors: 35

Interspecies AF, allometric scaling (dog to human): 1.4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 1

 

In conclusion, long term systemic oral DNEL, general population = 8.2 mg/kg bw/day.

 

 

References

(not included as endpoint study record)

 

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health.

 

- ECHA (2014). Guidance on information requirements and chemical safety assessment. Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics.