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EC number: 629-721-4 | CAS number: 308062-60-4
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.88 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA and ECETOC assessment factors with minor modification, see discussion for full justification.
- Overall assessment factor (AF):
- 10
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 8.8 mg/m³
- Explanation for the modification of the dose descriptor starting point:
ECHA guidance recommends that a factor of 2 be applied when doing route to route extrapolation for oral to inhalation exposure, recognizing higher absorption via the lungs. This additional assessment factor is not considered relevant in this particular case, since the substance has low vapour pressure and inhalation would have to be to an aerosol. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route of administration. Allometric scaling is applied by taking account for the different breathing rates between rats and humans, as described in ECHA technical guidance the oral NOAEL in the rat mg/kg/day *1/0.38 * 6.7/10 = mg/m3 inhalation NOAEC for workers.
- AF for dose response relationship:
- 1
- Justification:
- Default assessment factor going from NOAEL value with a clear dose-response relation, according to ECHA guidance document Chapter R8, in Table R. 8-6 Default assessment factors for issues related to dose-response.
- AF for differences in duration of exposure:
- 2
- Justification:
- Default assessment factor going from sub-chronic to chronic, according to ECHA guidance document Chapter R8, in Table R. 8-5 Assessment factors for duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No additional factor as already included in the route to route extrapolation from the rat oral NOAEL to the equivalent human inhalation NOAEC
- AF for other interspecies differences:
- 1
- Justification:
- ECETOC reported in 2010 after an extensive review (see discussion) that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied.
- AF for intraspecies differences:
- 5
- Justification:
- Default assessment factor for intraspecies variation for workers, according to ECHA guidance document Chapter R8, in Table R. 8-6 Default assessment factors for Intraspecies variation.
- AF for the quality of the whole database:
- 1
- Justification:
- According to ECHA guidance document Chapter R8, the default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1. Data used is based on testing of Amines, di-C16-18 (even-numbered) alkyl (CAS No. 308062-60-4) in a Klimisch 1 validity 90-day oral toxicity study performed according to GLP. Based on the quality of the available data an assessment factor of 1 is considered justified.
- AF for remaining uncertainties:
- 1
- Justification:
- Possible uncertainties are already included in the assessment factors above, so a factor of 1 is applied.
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.13 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA and ECETOC assessment factors with minor modification, see discussion for full justification.
- Overall assessment factor (AF):
- 40
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
ECHA guidance assumes that absorption for dermal exposure is the same as for oral exposure, which is a worst case assumption. Starting point is OECD 408 study by oral dosing in rats, resulting in a NOAEL of 5 mg/kg bw/day.
- AF for dose response relationship:
- 1
- Justification:
- Default assessment factor going from NOAEL value with a clear dose-response relation, according to ECHA guidance document Chapter R8, in Table R. 8-6 Default assessment factors for issues related to dose-response.
- AF for differences in duration of exposure:
- 2
- Justification:
- Default assessment factor going from sub-chronic to chronic, according to ECHA guidance document Chapter R8, in Table R. 8-5 Assessment factors for duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default assessment factor for allometric scaling between rat and human, according to ECHA guidance document Chapter R8, in Table R. 8-3 Allometric scaling factors for different species.
- AF for other interspecies differences:
- 1
- Justification:
- ECETOC reported in 2010 after an extensive scientific review (see discussion) that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied.
- AF for intraspecies differences:
- 5
- Justification:
- Default assessment factor for intraspecies variation for workers, according to ECHA guidance document Chapter R8, in Table R. 8-6 Default assessment factors for intraspecies variation.
- AF for the quality of the whole database:
- 1
- Justification:
- According to ECHA guidance document Chapter R8, the default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1. Data used is based on testing of Amines, di-C16-18 (even-numbered) alkyl (CAS No. 308062-60-4) in a Klimisch 1 validity 90-day oral toxicity study performed according to GLP. Based on the quality of the available data an assessment factor of 1 is considered justified.
- AF for remaining uncertainties:
- 1
- Justification:
- Possible uncertainties are already included in the assessment factors above, so a factor of 1 is applied.
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:
- no hazard identified
Additional information - workers
Selection of Assessment factors for Intra – Inter species variation for workers and the general population (consumers)
ECHA (2012) has produced guidance on the assessment factors to use to derive a DNEL for human exposure based the application of assessment factors (safety factors) to an NOAEL or LOAEL in animal studies.
The guidance proposes that an assessment factor of 2 to be applied when extrapolating from an oral NOAEL to an inhalation DNEL. However in the case of fatty nitriles and the related derivatives, their low vapour pressure minimises the potential for generating vapour, and thus the risk of inhaling these materials in general. In the unlikely event that particulates are inhaled the relatively large particle size compared to inhalation of a vapour, would be expected to impinge on the nasal passages and the upper respiratory tract. This would result in the particulates being ingested rather than being absorbed after entering the deep lung. Therefore, based on the physico-chemical properties of these chemicals, an assessment factor of 1 will be applied when extrapolating from oral NOAEL values to inhalation DNELs.
The ECHA guidance proposes an assessment factor of 4 for the allometric scaling from rats to humans when calculating dermal DNELs. However it then proposes an additional factor of 2.5 to cover remaining differences (uncertainties). There is no clear scientific justification for this additional factor. ECETOC in its Guidance on Assessment Factors to Derive DNELs (2010) reviewed the scientific evidence and concluded that the factor of 4 for rats was sufficient to cover the allometric scaling from rats to humans and any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.
References:
ECHA, 2012 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health. November 2012
ECETOC, 2010 Guidance on Assessment Factors to Derive DNELs,Technical Report110,ISSN-0773 -8072 -110, October 2010
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.22 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- other: ECHA and ECETOC assessment factors with minor modification, see discussion for full justification.
- Overall assessment factor (AF):
- 20
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 4.35 mg/m³
- Explanation for the modification of the dose descriptor starting point:
: ECHA guidance recommends that a factor of 2 be applied when doing route to route extrapolation for oral to inhalation exposure, recognizing higher absorption via the lungs. This additional assessment factor is not considered relevant in this particular case, since the substance has low vapour pressure and inhalation would have to be to an aerosol. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route of administration. Allometric scaling is applied by taking account for the different breathing rates between rats and humans, as described in ECHA technical guidance the oral NOAEL in the rat mg/kg/day *1/1.15 = mg/m3 inhalation NOAEC for general population.
- AF for dose response relationship:
- 1
- Justification:
- Default assessment factor going from NOAEL value with a clear dose-response relation, according to ECHA guidance document Chapter R8, in Table R. 8-6 Default assessment factors for issues related to dose-response.
- AF for differences in duration of exposure:
- 2
- Justification:
- Default assessment factor going from sub-chronic to chronic, according to ECHA guidance document Chapter R8, in Table R. 8-5 Assessment factors for duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No additional factor as already included in the route to route extrapolation from the rat oral NOAEL to the equivalent human inhalation NOAEC.
- AF for other interspecies differences:
- 1
- Justification:
- ECETOC reported in 2010 after an extensive scientific review (see discussion) that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied.
- AF for intraspecies differences:
- 10
- Justification:
- Default assessment factor for intraspecies variation for workers, according to ECHA guidance document Chapter R8, in Table R. 8-6 Default assessment factors for intraspecies variation.
- AF for the quality of the whole database:
- 1
- Justification:
- According to ECHA guidance document Chapter R8, the default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1. Data used is based on testing of Amines, di-C16-18 (even-numbered) alkyl (CAS No. 308062-60-4) in a Klimisch 1 validity 90-day oral toxicity study performed according to GLP. Based on the quality of the available data an assessment factor of 1 is considered justified.
- AF for remaining uncertainties:
- 1
- Justification:
- Possible uncertainties are already included in the assessment factors above, so a factor of 1 is applied.
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:
- 0.06 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA and ECETOC assessment factors with minor modification, see discussion for full justification.
- Overall assessment factor (AF):
- 80
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
ECHA guidance assumes that absorption for dermal exposure is the same as for oral exposure, which is a worst case assumption. Starting point is OECD 408 study by oral dosing in rats, resulting in a NOAEL of 5 mg/kg bw/day.
- AF for dose response relationship:
- 1
- Justification:
- Default assessment factor going from NOAEL value with a clear dose-response relation, according to ECHA guidance document Chapter R8, in Table R. 8-6 Default assessment factors for issues related to dose-response.
- AF for differences in duration of exposure:
- 2
- Justification:
- Default assessment factor going from sub-chronic to chronic, according to ECHA guidance document Chapter R8, in Table R. 8-5 Assessment factors for duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default assessment factor for allometric scaling between rat and human, according to ECHA guidance document Chapter R8, in Table R. 8-3 Allometric scaling factors for different species.
- AF for other interspecies differences:
- 1
- Justification:
- ECETOC reported in 2010 after an extensive scientific review (see discussion) that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied.
- AF for intraspecies differences:
- 10
- Justification:
- Default assessment factor for intraspecies variation for workers, according to ECHA guidance document Chapter R8, in Table R. 8-6 Default assessment factors for intraspecies variation.
- AF for the quality of the whole database:
- 1
- Justification:
- According to ECHA guidance document Chapter R8, the default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1. Data used is based on testing of Amines, di-C16-18 (even-numbered) alkyl (CAS No. 308062-60-4) in a Klimisch 1 validity 90-day oral toxicity study performed according to GLP. Based on the quality of the available data an assessment factor of 1 is considered justified.
- AF for remaining uncertainties:
- 1
- Justification:
- Possible uncertainties are already included in the assessment factors above, so a factor of 1 is applied.
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 DNEL required: short term exposure controlled by conditions for long-term
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.06 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- other:
- Overall assessment factor (AF):
- 80
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The DNEL is derived from a NOAEL in a 90 day oral study, so no route to route extrapolation is needed.
- AF for dose response relationship:
- 1
- Justification:
- Default assessment factor going from NOAEL value with a clear dose-response relation, according to ECHA guidance document Chapter R8, in Table R. 8-6 Default assessment factors for issues related to dose-response.
- AF for differences in duration of exposure:
- 2
- Justification:
- Default assessment factor going from sub-chronic to chronic, according to ECHA guidance document Chapter R8, in Table R. 8-5 Assessment factors for duration extrapolation.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default assessment factor for allometric scaling between rat and human, according to ECHA guidance document Chapter R8, in Table R. 8-3 Allometric scaling factors for different species.
- AF for other interspecies differences:
- 1
- Justification:
- ECETOC reported in 2010 after an extensive scientific review (see discussion) that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied.
- AF for intraspecies differences:
- 10
- Justification:
- Default assessment factor for intraspecies variation for workers, according to ECHA guidance document Chapter R8, in Table R. 8-6 Default assessment factors for intraspecies variation.
- AF for the quality of the whole database:
- 1
- Justification:
- According to ECHA guidance document Chapter R8, the default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1. Data used is based on testing of Amines, di-C16-18 (even-numbered) alkyl (CAS No. 308062-60-4) in a Klimisch 1 validity 90-day oral toxicity study performed according to GLP. Based on the quality of the available data an assessment factor of 1 is considered justified.
- AF for remaining uncertainties:
- 1
- Justification:
- Possible uncertainties are already included in the assessment factors above, so a factor of 1 is applied.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
Selection of Assessment factors for Intra – Inter species variation for workers and the general population (consumers)
ECHA (2012) has produced guidance on the assessment factors to use to derive a DNEL for human exposure based the application of assessment factors (safety factors) to an NOAEL or LOAEL in animal studies.
The guidance proposes that an assessment factor of 2 to be applied when extrapolating from an oral NOAEL to an inhalation DNEL. However in the case of fatty nitriles and the related derivatives, their low vapour pressure minimises the potential for generating vapour, and thus the risk of inhaling these materials in general. In the unlikely event that particulates are inhaled the relatively large particle size compared to inhalation of a vapour, would be expected to impinge on the nasal passages and the upper respiratory tract. This would result in the particulates being ingested rather than being absorbed after entering the deep lung. Therefore, based on the physico-chemical properties of these chemicals, an assessment factor of 1 will be applied when extrapolating from oral NOAEL values to inhalation DNELs.
The ECHA guidance proposes an assessment factor of 4 for the allometric scaling from rats to humans when calculating dermal DNELs. However it then proposes an additional factor of 2.5 to cover remaining differences (uncertainties). There is no clear scientific justification for this additional factor. ECETOC in its Guidance on Assessment Factors to Derive DNELs (2010) reviewed the scientific evidence and concluded that the factor of 4 for rats was sufficient to cover the allometric scaling from rats to humans and any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.
References:
ECHA, 2012
Guidance on information requirements and chemical safety assessment
Chapter R.8: Characterisation of dose [concentration]-response for human
health. November 2012
ECETOC, 2010 Guidance on Assessment Factors to Derive DNELs,Technical Report110,ISSN-0773 -8072 -110, October 2010
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