1-(vinyloxy)octadecane

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

14.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

6

Modified dose descriptor starting point:

NOAEC

Value:

88.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation available.

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:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

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:

3

Justification:

Intraspecies differences of worker are considered to be fully covered by the selected factor.

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:

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:

2.08 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

24

Modified dose descriptor starting point:

NOAEL

Value:

50 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No correction factor was used for calculation of oral to dermal absorption rate (100% dermal absorption as a worst case)

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:

2

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats 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:

3

Justification:

Intraspecies differences of worker are considered to be fully covered by the selected factor.

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

Most sensitive endpoint:

acute toxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

General

 

DNEL derivation for 1 -(vinyloxy)octadecane is performed under consideration of the recommendations of ECHA REACH guidance (2010) and ECETOC (2003).

 

Acute/ short-term- systemic effects

 

Short-term DNELs are not required as the acute toxicity is low. 1 -(Vinyloxy)octadecane is not classified and labelled for acute systemic toxicity, according to Regulation (EC) No 1272/2008 (CLP), based on the available test data for acute oral and dermal toxicity.

 

Acute/short-term and long-term exposure - local effects

 

1 -(Vinyloxy)octadecane is not classified for skin and eye irritation based on the results of the skin and eye irritation studies available (BASF, 1988). Therefore, no local assessment regarding to irritating effects has to be done.

 

Skin sensitisation: Since 1 -(vinyloxy)octadecane exhibits a skin sensitizing potential in the available LLNA (BASF 2012) a qualitative approach is used for risk assessment.

 

Respiratory irritation: No inhalation study is available. As no eye irritation properties were identified in the available eye irritation study and due to the low vapor pressure, respiratory irritation is not likely to occur.

 

Long term, systemic DNEL

Occupational exposure occurs mainly by dermal route, and may also occur 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" and "dose-response factor" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

Exposure by inhalation

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

The OECD TG 408 study (BASF, 2016) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL based on liver toxicity in rats is 50 mg/kg bw/day.

 

Step 2: Modification into a correct starting point:

Based on physico- chemical properties (log Kow: 9 and practically insoluble in water), it is assumed that the substance is not completely absorbed by inhalation exposure and that the inhalation absorption factor doesn’t exceed oral absorption factor.

 

Relevant dose descriptor (NOAEL): 50 mg/kg bw/d

Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d

Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / ABSinh-human): 1

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

 

Corrected inhalatory NOAEC for workers

= 50 mg/kg bw/d × (1 / 0.38 m³/kg bw/d) × (6.7 m³/10 m³)

= 88.2 mg/m³

 

Step 3: Use of assessment factors: 6

Interspecies: no allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed.

Intraspecies AF (worker): 3

Exposure duration AF: 2

 

In conclusion, long term systemic inhalation DNEL, workers = 14.7 mg/m³ (saturated vapor concentration at 20°C: 0.08 mg/m3)

 

Dermal exposure

 

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

The OECD TG 408 study (2016) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL, based on liver toxicity in rats is 50 mg/kg bw/day.

 

Step 2: Modification into a correct starting point:

No correction factor was used for calculation of oral to dermal absorption rate (100% dermal absorption as a worst case). In conclusion, dermal NOAEL = oral NOAEL x [ABS oral rat /ABS dermal human] = 50 x (100/100) = 50 mg/kg bw/d.

 

Step 3: Use of assessment factors: 24

Interspecies AF, allometric scaling (rat to human): 4

Intraspecies AF (worker): 3

Exposure duration AF: 2

 

In conclusion, long term systemic dermal DNEL, workers = 2.08 mg/kg bw/day

 

References

(not included as endpoint study record)

 

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2. ECHA-2010 -G-19 –EN.

 

- ECETOC Technical Report No. 110 (2010). Guidance on assessment factors to derive a DNEL.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.75 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

10

Modified dose descriptor starting point:

NOAEC

Value:

37.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation.

The recommended approach using oral data and assuming the same absorption for inhalation and oral route is used. For details, please refer to the discussion.

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:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

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:

Intraspecies differences of general population are considered to be fully covered by the selected factor.

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:

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:

1.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

Value:

50 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No correction factor was used for calculation of oral to dermal absorption rate (100% dermal absorption as a worst case)

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:

2

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats 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:

Intraspecies differences of general population are considered to be fully covered by the selected factor.

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)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

Value:

50 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation is required since a repeated dose oral toxicity study is available.

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:

2

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats 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:

Intraspecies differences of general population are considered to be fully covered by the selected factor.

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

Most sensitive endpoint:

acute toxicity

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

General

 

DNEL derivation is performed under consideration of the recommendations of ECHA REACH guidance (2010) and ECETOC (2003).

 

Acute/ short-term- systemic effects

 

Short-term DNELs are not required as the acute toxicity is low. 1 -(Vinyloxy)octadecane is not classified and labelled for acute systemic toxicity, according to Regulation (EC) No 1272/2008 (CLP), based on the test data for acute oral and dermal toxicity.

 

Acute/Long-term- local effects

 

1 -(Vinyloxy)octadecane is not classified for skin and eye irritation based on the results of the skin and eye irritation studies (BASF, 1988). Therefore, no local assessment regarding to irritating effects has to be done.

 

Since 1 -(vinyloxy)octadecane exhibits a skin sensitizing potential in the available LLNA (BASF 2012) a qualitative approach is used for risk assessment.

 

Respiratory irritation: No inhalation study is available. As no eye irritation properties were identified in the available eye irritation study and due to the low vapor pressure, respiratory irritation is not likely to occur.

 

Long term, systemic DNEL

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

 

Exposure by inhalation

 

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

The OECD TG 408 study (BASF, 2016) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL, based on liver toxicity in rats is 50 mg/kg bw/day.

 

Step 2: Modification into a correct starting point:

Based on physico- chemical properties (log Kow: 9 and practically insoluble in water), it is assumed that the substance is not completely absorbed by inhalation exposure and that the inhalation absorption factor doesn’t exceed oral absorption factor.

 

Relevant dose descriptor (NOAEL): 50 mg/kg bw/d

Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / ABSinh-human): 1

AF for allometric scaling: 4

Body weight: 60 kg

General population respiratory volume (wRV) for 24 hours: 20 m³/person

 

Corrected inhalatory NOAEC for general population

= [(50 mg/kg bw/d / 4) × 60 kg] / 20 m³

= 37.5 mg/m³

 

Step 3: Use of assessment factors: 10

Intraspecies AF (general population): 5

Exposure duration AF: 2

 

In conclusion, long term, systemic inhalation DNEL, general population = 3.75 mg/m³ (saturated vapor concentration at 20°C: 0.08 mg/m3)

 

Dermal exposure

 

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

The OECD TG 408 study (2016) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL, based on liver toxicity in rats is 50 mg/kg bw/day.

 

Step 2: Modification into a correct starting point:

No correction factor was used for calculation of oral to dermal absorption rate (100% dermal absorption as a worst case). In conclusion, dermal NOAEL = oral NOAEL x [ABS oral rat /ABS dermal human] = 50 x (100/100) = 50 mg/kg bw/d.

 

Step 3: Use of assessment factors: 40

Interspecies AF, allometric scaling (rat to human): 4

Intraspecies AF (general population): 5

Exposure duration AF: 2

 

In conclusion, long term systemic dermal DNEL, general population = 1.25 mg/kg bw/day

 

Oral exposure:

 

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

The OECD TG 408 study (2016) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL, based on liver toxicity in rats is 50 mg/kg bw/day.

 

Step 2: Use of assessment factors: 40

Interspecies AF, allometric scaling (rat to human): 4

Intraspecies AF (general population): 5

Exposure duration AF: 2

 

In conclusion, long term systemic oral DNEL, general population = 1.25 mg/kg bw/day

 

References

(not included as endpoint study record)

 

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2. ECHA-2010 -G-19 –EN.

 

- ECETOC Technical Report 110 (2010). Guidance on assessment factors to derive a DNEL.