Reaction mass of ethoxylated N-oleyl-1,3-propanediamine, hydrofluorides of and ethoxylated N-palmityl-1,3-propanediamine, hydrofluorides of and ethoxylated N-stearyl-1,3-propanediamine, hydrofluorides of and olaflur

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.418 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):

5

Dose descriptor starting point:

NOAEL

Value:

1 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

2.09 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.

AF for interspecies differences (allometric scaling):

1

Justification:

Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

AF for other interspecies differences:

1

Justification:

There is no evidence for species differences in the general mode of action or kinetics.

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:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium 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:

1.43 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):

7

Dose descriptor starting point:

NOAEL

Value:

1 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

10 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Please refer to expalantion on hazard conclusion.

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:

1

Justification:

There is no evidence for species differences in the general mode of action or kinetics.

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:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Occupational exposure to the test substance occurs mainly by dermal route and 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", "dose-response factor", "other interspecies differences" and "remaining uncertainties" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

Hazard via inhalation route

Step 1: Selection of the relevant dose descriptor (starting point):
For risk characterisation an inhalation NOAEC was derived by route to route extrapolation. The oral NOAEL of 1 mg/kg bw/day, obtained from a chronic toxicity testing in dogs, was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

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): 1 mg/kg bw/day

Standard respiratory volume of the dog (sRVdog) for 8 hours: 0.16 m³/kg bw/day (Bide et al., 1997, pg viii)

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

 

NOAEC (Worker) inhalation = 1 mg/kg bw/day * 1/0.16 m³/kg bw/day * 6.7 m³/10 m³ * 0.5

                                                   = 2.09 mg/m³

 

Step 3: Use of assessment factors: 5 

Interspecies: Respiratory interspecies differences are fully covered by the modification of the NOAEC

Intraspecies AF (worker): 5

Exposure duration AF: 1 (chronic study, OECD 452)

 

DNEL (Worker) inhalation = 2.09 mg/m³ / 5

                              = 0.418 mg/m³

 

In conclusion, long term systemic inhalation DNEL (worker) inhalation = 0.418 mg/m³  

Hazard via dermal route:

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

For risk characterisation an inhalation NOAEC was derived by route to route extrapolation. The oral NOAEL of 1 mg/kg bw/day, obtained from a chronic toxicity testing in dogs, was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

Step 2: Modification into a correct starting point: 

Using a conservative approach, a worker DNEL (long-term dermal exposure) is derived. Based on the physic-chemical properties dermal absorption is possible. According to “Guidance on information requirements and chemical safety assessment chapter R7c: Endpoint specific Guidance” especially the high water solubility of 164 g/L and the log Pow of 1.94 enable penetration. Further, the test substance is classified as a skin irritant, cat. 2 (H315) and the damage to the skin surface can enhance penetration. But based on the high molecular weight, between 470.22 to 498.77 g/mol, penetration of Olaflur will be limited. A dermal absorption of 10% of oral absorption is assumed as worst case.

NOAEC (Worker) dermal = 1 mg/kg bw/day / 0.1

                                            = 10 mg/kg bw/day

Step 3: Use of assessment factors: 7

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

Intraspecies AF (worker): 5

Exposure duration AF: 1 (chronic study, OECD 452)

DNEL (Worker) dermal = 10 mg/kg bw/day / 7

= 1.43 mg/kg bw/day

 

In conclusion, long term systemic dermal DNEL, workers = 1.43 mg/kg bw/day

Taking the acute oral toxicity data obtained into consideration, Olaflur might pose a minor risk to human health. In due consideration of the risk management measures suggested while handling Olaflur, immediate risk for human health (workers) can be excluded. Risk assessment of general public relevant only via cosmetic exposure, has been addressed in the respective safety dossier for cosmetic products and demonstrated that no risk for consumers (expected via cosmetic formulation) are to be expected.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.104 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Overall assessment factor (AF):

10

Dose descriptor starting point:

NOAEL

Value:

1 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

1.04 mg/m³

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

Justification:

Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

AF for other interspecies differences:

1

Justification:

There is no evidence for species differences in the general mode of action or kinetics.

AF for intraspecies differences:

10

Justification:

The default value for the relatively homogenous 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:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.71 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Overall assessment factor (AF):

14

Dose descriptor starting point:

NOAEL

Value:

1 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

10 mg/kg bw/day

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:

1

Justification:

There is no evidence for species differences in the general mode of action or kinetics.

AF for intraspecies differences:

10

Justification:

The default value for the relatively homogenous 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:

medium hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.07 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):

14

Dose descriptor starting point:

NOAEL

Value:

1 mg/kg bw/day

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:

1

Justification:

There is no evidence for species differences in the general mode of action or kinetics.

AF for intraspecies differences:

10

Justification:

The default value for the relatively homogenous 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:

medium hazard (no threshold derived)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

In view of the data used for evaluation, the "quality of whole database factor", "dose-response factor", "other interspecies differences" and "remaining uncertainties" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

Hazard via inhalation route

Step 1: Selection of the relevant dose descriptor (starting point):
For risk characterisation an inhalation NOAEC was derived by route to route extrapolation. The oral NOAEL of 1 mg/kg bw/day, obtained from a chronic toxicity testing in dogs, was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

Step 2: Modification into a correct starting point: 

Relevant dose descriptor (NO(A)EL): 1 mg/kg bw/day

Standard respiratory volume of the dog (sRVdog) for 24 hours: 0.48 m³/kg bw/day (Bide et al, 1997)

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

NOAEC (Worker) inhalation = 1 mg/kg bw/day * 1/0.48 m³/kg/ bw/day * 0.5

                                                  = 1.04 mg/m³

 

Step 3: Use of assessment factors: 10 

Interspecies: Respiratory interspecies differences are fully covered by the modification of the NOAEC

Intraspecies AF (general population): 10

Exposure duration AF: 1 (chronic study, OECD 452)

 

DNEL (general population) inhalation = 1.04 mg/m³ / 10

                                              = 0.104 mg/m³

 

In conclusion, long term systemic inhalation DNEL (general population) inhalation = 0.104 mg/m³  

Hazard via dermal route:

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

For risk characterisation an inhalation NOAEC was derived by route to route extrapolation. The oral NOAEL of 1 mg/kg bw/day, obtained from a chronic toxicity testing in dogs, was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

Step 2: Modification into a correct starting point: 

Using a conservative approach, a general population DNEL (long-term dermal exposure) is derived. Based on the physical-chemical properties dermal absorption is possible. According to “Guidance on information requirements and chemical safety assessment chapter R7c: Endpoint specific Guidance” especially the high water solubility of 164 g/L and the log Pow of 1.94 enable penetration. Further, the test substance is classified as a skin irritant, cat. 2 (H315) and the damage to the skin surface can enhance penetration. But based on the high molecular weight, between 470.22 to 498.77 g/mol, penetration of Olaflur will be limited. A dermal absorption of 10% of oral absorption is assumed as worst case.

NOAEC (general population) dermal = 1 mg/kg bw/day / 0.1

                                             = 10 mg/kg bw/day

Step 3: Use of assessment factors: 14

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

Intraspecies AF (general population): 10

Exposure duration AF: 1 (chronic study, OECD 452)

DNEL (general population) dermal = 10 mg/kg bw/day / 14

= 0.71 mg/kg bw/day

 

In conclusion, long term systemic dermal DNEL, general population = 0.71 mg/kg bw/day

Hazard via oral route:

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

The oral repeated-dose study in rats/dogs performed according to OECD guideline 452 is selected for DNEL derivation. In this study, the oral NOAEL in rats and dogs is 1 mg/kg bw/day.

Step 2: Modification into a correct starting point: 

Not required.

Step 3: Use of assessment factors: 14

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

Intraspecies AF (general population): 10

Exposure duration AF: 1 (chronic study, OECD 452)

DNEL (general population) oral = 1 mg/kg bw/day / 14

= 0.07 mg/kg bw/day

In conclusion, long term systemic oral DNEL, general population = 0.07 mg/kg bw/day

Taking the acute oral toxicity data obtained into consideration, Olaflur might pose a minor risk to human health. Risk assessment of general public relevant only via cosmetic exposure, has been addressed in the respective safety dossier for cosmetic products and demonstrated that no risk for consumers (expected via cosmetic formulation) are to be expected.