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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:
17.632 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

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:
10 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

In general, the calculation of a DNEL is based on the observed effect level which has to be modified as described in “Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health” (ECHA, May 2008).

Long-term dermal and inhalative intakes are the possible exposure routes for workers, whereas oral, dermal and inhalative intakes are the possible exposure routes for the general population. Together with the fact that no substance-related acute local and systemic systemic effects could be determined, only the DNEL for long-term systemic effects are derived since they have greater toxicological significance.

 

For the derivation of DNEL, the NOAEL of 1000 mg/kg bw/d (for systemic effects) was used which was found in a study performed according to OECD 422 where the males were treated by gavage for 42 days with docosanoic acid (Nagao, T., et al., 2002).

An substance-specific adjustment of the NOAEL is not performed since the obtained value of 1000 mg/kg bw reflects the worst case for fatty acids within the category as the molecular weight of docosanoic acid is the highest among all members.

 

Inhalative

For calculation of the DNEL for long-term inhalative systemic effects, the dose descriptor has to be converted into a corrected starting point by route-to-route extrapolation. The absorption difference for inhalation compared to the oral route is reflected by the factor 2 as suggested by the R.8. Besides this, the interspecies difference between rat and human has to be taken into account. Therefore, the no observed effect level has to be corrected by the risk assessor 6.7 / 0.38*10 regarding breathing volume and frequency. Thus, the corrected starting point for workers was 881.6 mg/m3/d for inhalation.

Subsequently other assessment factors are listed, which have to be taken into account for the final DNEL calculation: remaining interspecies-differences (2.5), intraspecies differences (5), exposure duration (4). The DNEL is calculated according to the formula DNEL = (corrected starting point)/(overall AF). Thus, the resulting DNEL for long-term inhalative systemic effects is 17.632 mg/m3for workers.

 

Dermal

For calculation of the DNEL for long-term dermal systemic effects, the dose descriptor has to be converted into a corrected starting point by route-to-route extrapolation. The absorption difference for the dermal route compared to the oral route is adjusted by the factor 0.5 due to the skin absorption classification as moderate based on the QSAR result for hexanoic acid (Danish EPA Database, 2004). This fatty acid has the highest absorption rate among all members of the category with 0.021 mg/cm2reflecting the worst case for all category members. Thus the corrected starting point for workers was 2000 mg/kg bw for the dermal route.

Subsequently, following assessment factors are taken into account for the final DNEL calculation: interspecies differences (4), remaining interspecies-differences (2.5), intraspecies differences (5), exposure duration (4).

As a consequence, the resulting DNEL for long-term dermal systemic effects is 10.0 mg/kg bw/d for workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.348 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

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:
5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
400
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
400
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

In general, the calculation of a DNEL is based on the observed effect level which has to be modified as described in “Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health” (ECHA, May 2008).

Long-term dermal and inhalative intakes are the possible exposure routes for workers, whereas oral, dermal and inhalative intakes are the possible exposure routes for the general population. Together with the fact that no substance-related acute local and systemic systemic effects could be determined, only the DNEL for long-term systemic effects are derived since they have greater toxicological significance.

 

For the derivation of DNEL, the NOAEL of 1000 mg/kg bw/d (for systemic effects) was used which was found in a study performed according to OECD 422 where the males were treated by gavage for 42 days with docosanoic acid (Nagao, T., et al., 2002).

An substance-specific adjustment of the NOAEL is not performed since the obtained value of 1000 mg/kg bw reflects the worst case for fatty acids within the category as the molecular weight of docosanoic acid is the highest among all members.

 

Inhalative

For calculation of the DNEL for long-term inhalative systemic effects, the dose descriptor has to be converted into a corrected starting point by route-to-route extrapolation. The absorption difference for inhalation compared to the oral route is reflected by the factor 2 as suggested by the R.8. Besides this, the interspecies difference between rat and human has to be taken into account. Therefore, the no observed effect level has to be corrected by the risk assessor 1/1.15 regarding breathing volume and frequency. Thus, the corrected starting point for the general population is 434.8 mg/m3/d for inhalation.

Subsequently other assessment factors are listed, which have to be taken into account for the final DNEL calculation: remaining interspecies-differences (2.5), intraspecies differences (10), exposure duration (4).

The DNEL is calculated according to the formula DNEL = (corrected starting point)/(overall AF). Thus, the resulting DNEL for long-term inhalative systemic effects is 4.348 mg/m3 for the general population.

 

Oral

For the DNEL of systemic oral effects a correction of the starting point is not required, since the observed effect level was derived in oral repeated dose toxicity study (Nagao, T., et al., 2002).

Subsequently, following assessment factors are taken into account for the final DNEL calculation: interspecies differences (4), remaining interspecies-differences (2.5), intraspecies differences (10), exposure duration (4). The resulting DNEL for long-term oral systemic effects is 2.5 mg/kg bw/d for the general population

Dermal

For calculation of the DNEL for long-term dermal systemic effects, the dose descriptor has to be converted into a corrected starting point by route-to-route extrapolation. The absorption difference for the dermal route compared to the oral route is adjusted by the factor 0.5 due to the skin absorption classification as moderate based on the QSAR result for hexanoic acid (Danish EPA Database, 2004). This fatty acid has the highest absorption rate among all members of the category with 0.021 mg/cm2reflecting the worst case for all category members. Thus the corrected starting point for workers was 2000 mg/kg bw for the dermal route.

Subsequently, following assessment factors are taken into account for the final DNEL calculation: interspecies differences (4), remaining interspecies-differences (2.5), intraspecies differences (10), exposure duration (4). The resulting DNEL for long-term dermal systemic effects is 5.0 mg/kg bw/d for the general population.