Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.88 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):
15
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
88.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAECcorr=NOAELoral*(1/0.38 m3 /kg/d)*(ABSoral-rat/ABSinhhuman)*(6.7 m3 (8h)/10 m3 (8h)) = 100 mg/kg/d*(1/0.38 m3 /kg/d)*(0.5*1)*0.67=88.2 mg/m3

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
2.5
AF for other interspecies differences:
1
Justification:
Accounted for by allometric scaling.
AF for intraspecies differences:
3
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.76 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):
7.5
DNEL extrapolated from long term DNEL

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:
4.2 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):
24
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to Guidance on information requirements and chemical safety assessment Chapter R.8. Characterisation of dose [concentration]-response for human health, Section R.8.4.3.1. Tables R.8-3 and R.8-4, pages 30-32.
AF for dose response relationship:
1
Justification:
Starting Point is a NOAEL
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8. Characterisation of dose [concentration]-response for human health Section R.8.4.3.1. Table R.8-3. page 30.
AF for other interspecies differences:
1
Justification:
Accounted for by allometric scaling.
AF for intraspecies differences:
3
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8. Characterisation of dose [concentration]-response for human health Appendix R.8-3, Table R.8-19, page 76.
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Worker acute/short-term exposure DNELs for dermal and inhalation systemic effects cannot be established because no adverse findings were made in acute laboratory animal studies. A skin DNEL cannot be established based upon the available guinea pig skin sensitization studies. Furthermore, toxicokinetic studies with 2,3-epoxypropyl neodecanoate demonstrate that there is little or no penetration of human skin. There were no acute/short-term adverse local effects upon which to base a Worker dermal or inhalation DNEL. 2,3 -Epoxypropyl neodecanoate is not a skin irritant and did not produce evidence of local nasal tract irritation in a 4 hr acute rat inhalation study conducted upto the saturation vapor concentration. There is no relevant data available upon which to base a Worker long-term exposure-local effects DNEL for dermal or inhalation exposure. 2,3 -Epoxypropyl neodecanoate was not a skin irritant in standard rabbit skin iritation tests. The test substance did not induce any evidence of local nasal tract irritation in a 4 hr rat acute inhalation toxicity study. 2,3 -Epoxypropyl neodecanoate is a skin sensitizer in the guinea pig Maximization test. There is insufficient dose-responce data from these studies to establish a quantitative risk assessment for dermal sensitization. However, limited human patch testing data suggest that a level of 2,3 -epoxypropyl neodecanoate of 0.01% is capable of eliciting positive dermal reactions in a previously sensitized individual.

A Worker Long-term exposure systemic effects Inhalation DNEL is based on the NOAEL of 100 mg/kg bw/day 2,3 -epoxypropyl neodecanoate in a 90 -day oral study conducted in rats. Based on E.C.H.A. guidance (RIP 3.2, Chapter R.8, Figure R.8 -3, page 27) the NOAEL value of 100 mg/kg/day is converted to a human equivalent inhalation value of 88.2 mg/m3. The following E.C.H.A. recommended Assessment Factors are applied: Interspecies = 2.5x; Intraspecies (worker) = 3x; Study duration (Subchronic to chronic) = 2x. Therefore, the total Assessment Factor applied to the NOAEL of 88.2 mg/m3 is 15. The resulting Worker inhalation Long-term exposure systemic effects DNEL = 5.88 mg/m3 TWA.

To derive a Worker Dermal Long-term systemic effects DNEL, allometric scalling is required (E.C.H.A. RIP 3.2, Chapter R.8, Section R.8.4.3.1, Tables R.8 -3 and 8 -4). An allometric scalling factor of 4x is applied to the NOAEL of 100 mg/kg/day from the five-week rat oral study. Further Assessment Factors applied are: Intraspecies (worker) = 3x; Study duration (subchronic to chronic) = 2x. No additional Interspecies Assessment Factor is necessary because the results of toxicokinetic studies demonstrated that penetration of human skin by 2,3 -epoxypropyl neodecanoate is approximately 10 -fold less than rat skin. The total Assessment Factor applied to the NOAEL is 24 resulting in a Worker dermal long-term systemic effects DNEL of approximately 4.2 mg/kg/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
88.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAECcorr=NOAELoral*(1/0.38 m3 /kg/d)*(ABSoral-rat/ABSinhhuman)*(6.7 m3 (8h)/10 m3 (8h)) = 100 mg/kg/d*(1/0.38 m3 /kg/d)*(0.5*1)*0.67=88.2 mg/m3
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
2.5
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8. Characterisation of dose [concentration]-response for human health page 33.
Justification:
Accounted for by allometric scaling.
AF for intraspecies differences:
5
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8. Characterisation of dose [concentration]-response for human health, Appendix R.8-3. Table R.8-19, page 76.
AF for the quality of the whole database:
1
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:
2.5 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):
40
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to Guidance on information requirements and chemical safety assessment Chapter R.8. Characterisation of dose [concentration]-response for human health, Section R.8.4.3.1. Tables R.8-3 and R.8-4, pages 30-32.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL.
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8. Characterisation of dose [concentration]-response for human health Section R.8.4.3.1. Table R.8-3. page 30.
AF for other interspecies differences:
1
Justification:
Accounted for by allometric scaling.
AF for intraspecies differences:
5
Justification:
According to Guidance on information requirements and chemical safety assessment Chapter R.8. Characterisation of dose [concentration]-response for human health, Appendix R.8-3. Table R.8-19, page 76.
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
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

General population Acute/short-term exposure systemic effects DNELs for 2,3 -epoxypropyl neodecanoate cannot be established because acute laboratory animal studies conducted by the oral, dermal and inhalations routes of exposure did not demonstrate any adverse systemic effects findings upon which to base DNEL values. Furthermore, as per ECHA guidance, Acute/short-term DNELs are only necessary for Worker peak inhalation exposure. Human ingestion of this substance is not anticipated based on the Chemical Safety Assessment. General population Acute/short-term exposure local effects DNELS cannot be established because portal-of-entry local effects were not significant in skin irritation and acute inhalation studies. There is insufficient dose-responce data from guinea pig Maximization studies to develop a risk assessment for dermal sensitization. However, limited human patch test data suggests that a concentration level of 0.01% 2,3 -epoxypropyl neodecanoate can elicite positive dermal reactions in previously sensitized individuals. Furthermore, According to the Guidance on information requirements and chemical safety assessment Chapter R.8. Characterisation of dose [concentration]-response for human health, Section 8.1.2.5. page 16, Acute/short-term DNELs are necessary only for Worker inhalation peak exposures.   

General Population Long-term local effects DNELs for dermal or inhalation exposure cannot be developed for 2,3 -epoxypropyl neodecanoate because no adverse local effects were observed in short or repeated-dose laboratory animal studies.

General population Long-term exposure systemic effects DNELs can be developed based on the NOAEL of 100 mg/kg/day from the 90 -day rat oral study. Allometric scalling as per E.C.H.A. guidance (E.C.H.A. RIP 3.2, Chapter R.8, Section R.8.4.3.1) is applied for dose conversion for the derivation of the oral and dermal DNELs.

For derivation of the General population Long-term exposure systemic effects inhalation DNEL the oral NOAEL of 100 mg/kg/day is converted to a human equivalent inhalation dose of 88.2 mg/m3 based on E.C.H.A. guidance ( E.C.H.A. RIP 3.2, Chapter R.8, Table R. 8 -3). The Assessment Factors applied to this value are: Interspecies Difference = 2.5x; Intraspecies Difference (General population) = 5; Study duration (subchronic to chronic) = 2x. Therefore, the total Assessment Factor applied is 25 and the resulting DNEL is 4.0 mg/m3.

In order to derive a Dermal Long-term exposure systemic effects DNEL, an allometric scalling factor of four is used to convert rat oral data to human data as per E.C.H.A. guidance (E.C.H.A. RIP 3.2, Chapter R.8, Section R.8.4.3.1, Table R. 8 -3, page 30). The NOAEL of 100 mg/kg/day from the 90 -day rat oral study is used to establish the Dermal DNEL value. An allometric scalling factor of 4 is applied. Following E.C.H.A. guidance these Assessment Factors are used: Intraspecies Difference (General population) = 5x; Study duration (subchronic to chronic) = 2x. An Interspecies Difference Assessment Factor is not necessary because toxicokinetic study data for 2,3 -epoxypropyl neodecanoate demonstrated that penetration of human skin is approximately 10 -fold less than rodent skin. The total Assessment Factor to be applied to the NOAEL of 100 mg/kg/day is 40. The resulting in a General population Long-term exposure systemic effects Dermal DNEL is 2.5 mg/kg/day.

It is generally recognized. based on use and the Chemical Safety Assessment, that there will be no exposure of the General population to 2,3 -epoxypropyl neodecanoate by the oral route. Therefore, a formal Risk Assessment for the General population for exposure to 2,3 -epoxypropyl neodecanoate by the oral route is unnecessary.