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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:
86 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: European Centre for Ecotoxicology and Toxicology of Chemicals Technical Report 110
Overall assessment factor (AF):
6
Dose descriptor starting point:
NOAEL
Value:
700 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
515.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

Substance specific information on oral absorption, but not inhalation absorption, is available for neodecanoic acid. A toxicokinetics study performed with14C-labelled neodecanoic acid in rats previously unexposed or preconditioned by five days of daily exposure to 100 mg/kg bw-d is available. The observed absorption of neodecanoic acid averaged ≥53.5% in male rats based on the recovery of 40.4% to 69.6% of the administered dose in urine. The observed absorption of neodecanoic acid averaged ≥41.8% in female rats based on the recovery of 32.9% to 69.6% of the administered dose in urine. Because fecal metabolites where not assessed it is impossible to tell if the fraction of the administered dose recovered in feces was absorbed or not. It is likely some fraction of fecally excreted compound was absorbed but eliminated via feces. This results in an underestimate of absorbed dose and thus a more conservative derivation of internal dose. Point of departure adjusted for oral absorption was slightly lower for female rats, thus that value is used to calcualte an absorption-adjusted NOAEL. Thus the NOAEL of 700 mg/kg-d multiplied by 41.8% oral absorption results in an absorption-adjusted NOAEL of 292.6 mg/kg/d.

The absorption-adjusted oral dose is converted to a corresponding air concentration using the standard breathing volume of a rat. The default physiological parameter under the allometric scaling principle from Table R.8 -2 for an eight hour exposure, 0.38 m3/kg bw was used. The absorption-adjusted NOAEL of 292.6 mg/kg/d is adjusted for respiration volume for rats (8 hours = 0.38 m^3/kg bw). The calculated rat NOAEC is therefore 292.6/0.38 = 770 mg/m^3.

The point of departure is further adjusted to account for differences between the 8 hour respiration volume of resting humans (6.7 m^3/person) and lightly working humans (10 m^3/person). The calculated value is 770 mg/m^3 * (6.7 m^3 per person / 10 m^3 per person) = 515.9 mg/m^3.

AF for dose response relationship:
1
Justification:
No human relevant adverse effects identified at the highest tested dose in the study
AF for differences in duration of exposure:
2
Justification:
This factor is the same suggested value in both ECETOC Technical Report 110 and ECHA's 2012 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for interspecies differences (allometric scaling):
1
Justification:
ECETOC and ECHA guidance indicates not to apply an interspecies allometric scaling factor for oral-to-inhalation route-to-route extrapolation
AF for other interspecies differences:
1
Justification:
No other potential assessment factor need identified
AF for intraspecies differences:
3
Justification:
Estimates for the upper 95th percentile variability distribution for both toxicokinetic and -dynamic parameters were 4.3 for the dataset of Renwick and Lazarus ("Human variability and noncancer risk assessment – an analysis of the default uncertainty factor." Regul Toxicol Pharmacol 27:3-20, 1998) and 3.8 for Hattis et al ("Human interindividual variability in parameters related to health risks." Risk Anal 19(4):711-726, 1999). Because the worker population is more homogenous a lower factor of 3 is justified.
AF for the quality of the whole database:
1
Justification:
All toxicology endpoints have been addressed through experimental data or read-across.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties 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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
29 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: European Centre for Ecotoxicology and Toxicology of Chemicals Technical Report 110
Overall assessment factor (AF):
24
Dose descriptor starting point:
NOAEL
Value:
700 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
700 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dose descriptor starting point is not modified (i.e., adjustment factor of 1) is used for oral to dermal extrapolation.

AF for dose response relationship:
1
Justification:
No human relevant adverse effects identified at the highest tested dose in the study
AF for differences in duration of exposure:
2
Justification:
This factor is the same suggested value in both ECETOC Technical Report 110 and ECHA's 2012 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for interspecies differences (allometric scaling):
4
Justification:
This factor is the same suggested value in both ECETOC Technical Report 110 and ECHA's 2012 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for other interspecies differences:
1
Justification:
Interspecies comparisons of rats and mice indicates an interspecies difference of 1.4 for these two species, a value closely corresponding to that calculated by allometry (7:4 = 1.75). This indicates an additional factor (e.g., 2.5) is not necessary, as interspecies differences are generally accounted for in allometric scaling. Further, because no adverse effects were observed there is no species-specific reason to expect differences between rats and humans.
AF for intraspecies differences:
3
Justification:
Estimates for the upper 95th percentile variability distribution for both toxicokinetic and -dynamic parameters were 4.3 for the dataset of Renwick and Lazarus ("Human variability and noncancer risk assessment – an analysis of the default uncertainty factor." Regul Toxicol Pharmacol 27:3-20, 1998) and 3.8 for Hattis et al ("Human interindividual variability in parameters related to health risks." Risk Anal 19(4):711-726, 1999). Because the worker population is more homogenous a lower factor of 3 is justified.
AF for the quality of the whole database:
1
Justification:
All toxicology endpoints have been addressed through experimental data or read-across.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Acute toxicity

A DNEL for acute toxicity should be derived if an acute hazard leading to acute toxicity (e.g. C&L) has been identified and there is a potential for high peak exposures. These “peaks” are normally associated with inhalation exposure but are less common for skin contact and ingestion (Appendix R.8-8). Neodecanoic acid is not classified for acute toxicity; oral, dermal or inhalation. 

 

Irritation

Neodecanoic acid is not classified as a skin irritant.  A DNEL is not required for this endpoint. 

 

Sensitization

Neodecanoic acid is not classified as a sensitizer. A DNEL is not required for this endpoint.   

 

Genetic toxicity

Neodecanoic acid is not classified as a genotoxic or mutagenic. A DNEL is not required for this endpoint. 

 

Reproductive and Developmental toxicity

A DNEL was derived for risk characterization for an exposure-based adaptation in replace of an EOGRTS study. The RCRs were developed from DNELs derived from a modified three-generation reproduction study in rats NOAEL value; and therefore, is directly applicable to the information requirement. The DNELs were highly conservative for reproductive toxicity effects. There were no adverse findings at the highest dose tested. An oral DNEL was not derived because neodecanoic acid is not used in professional use or consumer products; and therefore, no wide dispersive applications are considered in this evaluation

DNEL Derivation

Calculation of a Modified Point of Departure (Starting Point) by Route-to-Route Extrapolation (oral to inhalation)

 

An oral DNEL was not derived because neodecanoic acidis not used in professional use or consumer products; and therefore, no wide dispersive applications are considered in this evaluation.  This product is used as an intermediate in the manufacturing of other substance. The substance when manufactured is generally handled in closed contained systems with occasional potential for exposures.

 

Inhalation

Dose descriptor = NOAEL of 75/mg/kg/day; from a well described 3-generation reproduction and development study

 

Route-to-route extrapolation (calculation B.3 in ECHA Guidance R.8)

inhalatory NOAEC = oral LOAEL * (1/ sRV rat 8h) * (ABS oral / ABS inh) * (sRV human / wRV)

inhalatory NOAEC= 75 * (1/0.38) * (100/100) * (6.7 / 10)

inhalatory NOAEC = 132.24 mg/m3

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

 

Criteria

Adjustment Factor

Allometric scaling – rat

2.5

Intraspecies - workers

5

Subchronic study to Chronic 

2

Dose-response

1

Database quality

1

Overall Adjustment Factor

25

           

DNEL calculation

DNEL inhalation = inhalation NOAEC / (adjustment factors)

DNEL inhalation = 132.24 mg/m3/ (25)

DNEL inhalation = 5.29 mg/m3

 

 

Dermal - Systemic

Dose descriptor = Dose descriptor = NOAEL of 75/mg/kg/day; from a well described 3-generation reproduction and development study

 

Modification of dose descriptor

dermal NOAEL = oral NOAEL * (animal exposure / worker exposure) * (animal days / worker days) *)(oral abs / dermal abs)

= 75 * (8 / 8) * (4 / 5)* (100 / 10)

dermal NOAEL =  600 mg/kg/day

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

 

Criteria

Adjustment Factor

Allometric scaling - rat

10

Intraspecies - workers

5

Subchronic study to Chronic    

2

Dose-response

1

Database quality

1

Overall Adjustment Factor

100

  

DNEL calculation

DNEL dermal = dermal NOAEL / (adjustment factors)

DNEL dermal = 600 mg/kg/day / (100)

DNEL dermal = 6 mg/kg/day

 

Long-term systemic effects

The potential of a substance to cause long-term systemic effects can judged based on the results of repeated dose toxicity testing.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25.79 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: European Centre for Ecotoxicology and Toxicology of Chemicals Technical Report 110
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEL
Value:
700 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
257.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

Substance specific information on oral absorption, but not inhalation absorption, is available for neodecanoic acid. A toxicokinetics study performed with14C-labelled neodecanoic acid in rats previously unexposed or preconditioned by five days of daily exposure to 100 mg/kg bw-d is available. The observed absorption of neodecanoic acid averaged ≥53.5% in male rats based on the recovery of 40.4% to 69.6% of the administered dose in urine. The observed absorption of neodecanoic acid averaged ≥41.8% in female rats based on the recovery of 32.9% to 69.6% of the administered dose in urine. Because fecal metabolites where not assessed it is impossible to tell if the fraction of the administered dose recovered in feces was absorbed or not. It is likely some fraction of fecally excreted compound was absorbed but eliminated via feces. This results in an underestimate of absorbed dose and thus a more conservative derivation of internal dose. Point of departure adjusted for oral absorption was slightly lower for female rats, thus that value is used to calcualte an absorption-adjusted NOAEL. Thus the NOAEL of 700 mg/kg-d multiplied by 41.8% oral absorption results in an absorption-adjusted NOAEL of 292.6 mg/kg/d.

The absorption-adjusted oral dose is converted to a corresponding air concentration using the 24 -hour standard breathing volume of a rat. The default physiological parameter under the allometric scaling principle from Table R.8-2 for an 24 hour exposure, 1.15 m3/kg bw was used. The absorption-adjusted NOAEL of 292.6 mg/kg/d is adjusted for respiration volume for rats (1.15 m^3/kg bw). The calculated rat NOAEC is therefore 292.6/1.15 = 257.9 mg/m^3.

AF for dose response relationship:
1
Justification:
No human relevant adverse effects identified at the highest tested dose in the study
AF for differences in duration of exposure:
2
Justification:
This factor is the same suggested value in both ECETOC Technical Report 110 and ECHA's 2012 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for interspecies differences (allometric scaling):
1
Justification:
ECETOC and ECHA guidance indicates not to apply an interspecies allometric scaling factor for oral-to-inhalation route-to-route extrapolation
AF for other interspecies differences:
1
Justification:
No other potential assessment factor need identified
AF for intraspecies differences:
5
Justification:
The 95th or the 90th percentile for the intraspecies AF of the general human population can be estimated as approximately 6 and 4, respectively (ECETOC Technical Report 110). This justifies a factor of 5 instead of 10.
AF for the quality of the whole database:
1
Justification:
All toxicology endpoints have been addressed through experimental data or read-across.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties 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:
DNEL (Derived No Effect Level)
Value:
17.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: European Centre for Ecotoxicology and Toxicology of Chemicals Technical Report 110
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
700 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
700 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dose descriptor starting point is not modified (i.e., adjustment factor of 1) is used for oral to dermal extrapolation.

AF for dose response relationship:
1
Justification:
No human relevant adverse effects identified at the highest tested dose in the study
AF for differences in duration of exposure:
2
Justification:
This factor is the same suggested value in both ECETOC Technical Report 110 and ECHA's 2012 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for interspecies differences (allometric scaling):
4
Justification:
This factor is the same suggested value in both ECETOC Technical Report 110 and ECHA's 2012 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for other interspecies differences:
1
Justification:
Interspecies comparisons of rats and mice indicates an interspecies difference of 1.4 for these two species, a value closely corresponding to that calculated by allometry (7:4 = 1.75). This indicates an additional factor (e.g., 2.5) is not necessary, as interspecies differences are generally accounted for in allometric scaling. Further, because no adverse effects were observed there is no species-specific reason to expect differences between rats and humans.
AF for intraspecies differences:
5
Justification:
The 95th or the 90th percentile for the intraspecies AF of the general human population can be estimated as approximately 6 and 4, respectively (ECETOC Technical Report 110). This justifies a factor of 5 instead of 10.
AF for the quality of the whole database:
1
Justification:
All toxicology endpoints have been addressed through experimental data or read-across.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties have been 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:
17.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: European Centre for Ecotoxicology and Toxicology of Chemicals Technical Report 110
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
700 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
700 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification is suggested because the source study is oral

AF for dose response relationship:
1
Justification:
No human relevant adverse effects identified at the highest tested dose in the study
AF for differences in duration of exposure:
2
Justification:
This factor is the same suggested value in both ECETOC Technical Report 110 and ECHA's 2012 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for interspecies differences (allometric scaling):
4
Justification:
This factor is the same suggested value in both ECETOC Technical Report 110 and ECHA's 2012 Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health.
AF for other interspecies differences:
1
Justification:
Interspecies comparisons of rats and mice indicates an interspecies difference of 1.4 for these two species, a value closely corresponding to that calculated by allometry (7:4 = 1.75). This indicates an additional factor (e.g., 2.5) is not necessary, as interspecies differences are generally accounted for in allometric scaling. Further, because no adverse effects were observed there is no species-specific reason to expect differences between rats and humans.
AF for intraspecies differences:
5
Justification:
The 95th or the 90th percentile for the intraspecies AF of the general human population can be estimated as approximately 6 and 4, respectively (ECETOC Technical Report 110). This justifies a factor of 5 instead of 10.
AF for the quality of the whole database:
1
Justification:
All toxicology endpoints have been addressed through experimental data or read-across.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties identified
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

Acute toxicity

A DNEL for acute toxicity should be derived if an acute hazard leading to acute toxicity (e.g. C&L) has been identified and there is a potential for high peak exposures. These “peaks” are normally associated with inhalation exposure but are less common for skin contact and ingestion (Appendix R.8-8). Neodecanoic acid is not classified for acute toxicity; oral, dermal or inhalation. 

 

Irritation

Neodecanoic acid is not classified as a skin irritant.  A DNEL is not required for this endpoint. 

 

Sensitization

Neodecanoic acid is not classified as a sensitizer. A DNEL is not required for this endpoint.   

 

Genetic toxicity

Neodecanoic acid is not classified as a genotoxic or mutagenic. A DNEL is not required for this endpoint. 

 

Reproductive and Developmental toxicity

Neodecanoic acid is not classified as a reproductive or developmental toxin. A DNEL is not required for this endpoint. 

 

Long-term systemic effects

The potential of a substance to cause long-term systemic effects can judged based on the results of repeated dose toxicity testing.