N-methyl-N-vinylacetamide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

NOAEC

Value:

50 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

35.175 mg/m³

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation was used as one repeated inhalation exposure study was available. For details on calculations please refer to 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:

4

Justification:

As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of 30 days (males) and 56 days (females) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

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:

DNEL (Derived No Effect Level)

Value:

0.028 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

12.5

Dose descriptor:

NOAEC

Value:

0.5 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 is conducted for local DNEL derivation.

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.2 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Dose descriptor starting point:

NOAEC

Value:

50 mg/m³

Modified dose descriptor starting point:

NOAEL

Value:

39.9 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by dermal route. For details on calculations please refer to 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:

4

Justification:

As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of 30 days (males) and 56 days (females) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.

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:

2.5

Justification:

Recommended AF for other interspecies differences.

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:

low hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

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:

low hazard (no threshold derived)

Additional information - workers

WORKER

 

General

DNEL derivation for the test substance is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

Workers – Hazard via inhalation route

 

Long term systemic inhalation DNEL, worker

The DNEL long term, systemic (inhalation) is derived from the repeated dose inhalation toxicity study.

 

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

The repeated dose toxicity study 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 inhalation NOAEC (systemic) is 50 mg/m^3.

 

Step 2: Modification of the starting point:

No modification for absorption is used as the same exposure route is considered. Following corrections were performed:

 

Relevant dose descriptor (NOAEC): 50 mg/m^3

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

Frequency of exposure in study: 7 days/week, 6 hours/day

Frequency of worker exposure: 5 days/week, 8 hours/day

 

Corrected inhalatory NOAEC for workers

= 50 mg/m^3 * (6.7 m³/10 m³) * (7/5) * (6/8)

= 35.175 mg/m³

 

Step 3: Use of assessment factors: 50

Interspecies AF, allometric scaling (rat to human): 1

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5 

Exposure duration AF: 4

Remaining uncertainties AF: 1

 

In conclusion, long term systemic inhalation DNEL, worker = 0.7035 mg/m^3

 

Short term systemic inhalation DNEL, worker

The test material is not classified and labelled for acute systemic toxicity (inhalation), according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

  

Long term local inhalation DNEL, worker

The DNEL long term, local (inhalation) is derived from the repeated dose inhalation toxicity study.

 

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

The repeated dose toxicity study 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 inhalation NOAEC (local) is 0.5 mg/m^3.

 

Step 2: Modification of the starting point:

No modification for absorption is used as the same exposure route is considered. Following corrections were performed:

 

Relevant dose descriptor (NOAEC): 0.5 mg/m^3

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

Frequency of exposure in study: 7 days/week, 6 hours/day

Frequency of worker exposure: 5 days/week, 8 hours/day

 

Corrected inhalatory NOAEC for workers

= 0.5 mg/m^3 * (6.7 m³/10 m³) * (7/5) * (6/8)

= 0.35175 mg/m³

 

Step 3: Use of assessment factors: 12.5

Interspecies AF, allometric scaling (rat to human): 1

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5 

Exposure duration AF: 1  (No time extrapolation is conducted for local DNEL derivation.)

Remaining uncertainties AF: 1

 

In conclusion, long term local inhalation DNEL, worker = 0.02814 mg/m^3

 

Short term local inhalation DNEL, worker

Short term local inhalation effects are covered by the long term local risk assessment and no quantitative acute local inhalation assessment is required (in accordance with "Guidance on information requirements and chemical safety assessment", Part E).

 

 

Workers – Hazard via dermal route

Long term systemic dermal DNEL, worker

The DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose inhalation toxicity study.

 

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

The repeated dose toxicity study 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 inhalation NOAEC is 50 mg/m^3.

 

Step 2: Modification of the starting point:

Due to the physic-chemical properties the dermal uptake is considered to be 50 % of the inhalation uptake in the worst case.

 

Factor for dermal NOAEL= 100 % inhalation / 50 % dermal= 2

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

Frequency of exposure in study: 7 days/week, 6 hours/day

Frequency of worker exposure: 5 days/week, 8 hours/day

 

inhalation NOAEC 50 mg/m^3 * 2 * 0.38 m³/kg bw/d * (7/5) * (6/8)= 39.9 mg/kg bw/day dermal NOAEL

 

Step 3: Use of assessment factors: 200

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 4

Remaining uncertainties AF: 1

 

In conclusion, long term systemic dermal DNEL, workers = 0.1995 mg/kg bw/day.

 

 

Long term local dermal DNEL, worker

The test material is not classified and labelled for skin sensitization or skin irritation, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

Short term local dermal DNEL, worker

The test material is not classified and labelled for skin sensitization or skin irritation, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

 

Worker – Hazard for the eyes

For exposure to the eyes a low hazard was identified, as the test substance is classified for eye irritation Cat.2 according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E).

 

References

(not included as endpoint study record)

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.

- ECHA (2014). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. November 2014.

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

- ECHA (2016). Guidance on information requirements and chemical safety assessment.Part E: Risk Characterisation, Version 3.0, May 2016.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.125 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

NOAEC

Value:

50 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

12.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation was used as one repeated inhalation exposure study was available. For details on calculations please refer to 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:

4

Justification:

As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of 30 days (males) and 56 days (females) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

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:

DNEL (Derived No Effect Level)

Value:

0.005 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor:

NOAEC

Value:

0.5 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 is conducted for local DNEL derivation.

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

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

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.072 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

400

Dose descriptor starting point:

NOAEC

Value:

50 mg/m³

Modified dose descriptor starting point:

NOAEL

Value:

28.75 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by dermal route. For details on calculations please refer to 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:

4

Justification:

As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of 30 days (males) and 56 days (females) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.

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:

2.5

Justification:

Recommended AF for other interspecies differences.

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:

DNEL (Derived No Effect Level)

Value:

0.216 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

3

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

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.036 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

400

Dose descriptor starting point:

NOAEC

Value:

50

Modified dose descriptor starting point:

NOAEL

Value:

14.375 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by oral route. For details on calculations please refer to 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:

4

Justification:

As the NOAEL of a repeated dose toxicity study (OECD 422) with an exposure time of 30 days (males) and 56 days (females) was used as point of departure an AF of 4 is considered as adequate for the exposure duration extrapolation.

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:

2.5

Justification:

Recommended AF for other interspecies differences.

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:

DNEL (Derived No Effect Level)

Value:

0.108 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

3

DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - General Population

General Population

 

General

DNEL derivation for the test substance is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

General population – Hazard via inhalation route

Long term systemic inhalation DNEL, General population

The DNEL long term, systemic (inhalation) is derived from the repeated dose inhalation toxicity study.

 

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

The repeated dose toxicity study 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 inhalation NOAEC (systemic) is 50 mg/m^3.

 

Step 2: Modification of the starting point:

No modification for absorption is used as the same exposure route is considered. Following corrections were performed:

 

Relevant dose descriptor (NOAEC): 50 mg/m^3

Frequency of exposure in study: 7 days/week, 6 hours/day

Frequency of general population exposure: 7 days/week, 24 hours/day

 

Corrected inhalatory NOAEC for general population

= 50 mg/m^3 * (6/24)

= 12.5 mg/m³

 

 

Step 3: Use of assessment factors: 100

Interspecies AF, allometric scaling (rat to human): 1

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 4

Remaining uncertainties AF: 1

 

In conclusion, long term systemic inhalation DNEL, general population = 0.125 mg/m^3

 

Short term systemic inhalation DNEL, General population

The test material is not classified and labelled for acute systemic toxicity (inhalation), according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

Long term local inhalation DNEL, General population

The DNEL long term, local (inhalation) is derived from the repeated dose inhalation toxicity study.

 

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

The repeated dose toxicity study 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 inhalation NOAEC (local) is 0.5 mg/m^3.

 

Step 2: Modification of the starting point:

No modification for absorption is used as the same exposure route is considered. Following corrections were performed:

 

Relevant dose descriptor (NOAEC): 0.5 mg/m^3

Frequency of exposure in study: 7 days/week, 6 hours/day

Frequency of general population exposure: 7 days/week, 24 hours/day

 

 

Corrected inhalatory NOAEC for general population

= 0.5 mg/m^3 * (6/24)

= 0.125 mg/m³

 

Step 3: Use of assessment factors: 25

Interspecies AF, allometric scaling (rat to human): 1

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10  

Exposure duration AF: 1  (No time extrapolation is conducted for local DNEL derivation.) 

Remaining uncertainties AF: 1

 

In conclusion, long term local inhalation DNEL, general population = 0.005 mg/m^3

 

Short term local inhalation DNEL, General population

Short term local inhalation effects are covered by the long term local risk assessment and no quantitative acute local inhalation assessment is required (in accordance with "Guidance on information requirements and chemical safety assessment", Part E).

 

 

General population – Hazard via dermal route

Long term systemic dermal DNEL, General population

The DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose inhalation toxicity study.

 

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

The repeated dose toxicity study 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 inhalation NOAEC is 50 mg/m^3.

 

Step 2: Modification of the starting point:

Due to the physic-chemical properties the dermal uptake is considered to be 50 % of the inhalation uptake in the worst case.

 

Factor for dermal NOAEL= 100 % inhalation / 50 % dermal= 2

Standard respiratory volume of the rat (sRVrat) for 24 hours: 1.15 m³/kg bw/d

Frequency of exposure in study: 7 days/week, 6 hours/day

Frequency of general population exposure: 7 days/week, 24 hours/day

 

inhalation NOAEC 50 mg/m^3 * 2 * 1.15 m³/kg bw/d * (6/24)= 28.75 mg/kg bw/day dermal NOAEL

 

Step 3: Use of assessment factors: 400

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 4

Remaining uncertainties AF: 1

 

In conclusion, long term systemic dermal DNEL, general population = 0.071875 mg/kg bw/day

 

Short term systemic dermal DNEL, General population

The test material is classified for acute dermal toxicity cat. 4, according to Regulation (EC) No 1272/2008 (CLP). The acute systemic DNEL (dermal) is extrapolated from the long term DNEL with multiplication by factor of 3 (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). The long term systemic DNEL (dermal) is derived from the repeated dose inhalation toxicity study.

For Steps 1-3 please refer to “Long term systemic dermal DNEL, General population”

 

Step 4: extrapolation from the long term DNEL

A factor of 3 is used: long term DNEL*3= short term DNEL

0.071875*3=0.215625 mg/kg bw/day

In conclusion, short term systemic dermal DNEL, general population = 0.215625 mg/kg bw/day

 

Long term local dermal DNEL, General population

The test material is not classified and labelled for skin sensitization or skin irritation, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

Short term local dermal DNEL, General population

The test material is not classified and labelled for skin sensitization or skin irritation, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

 

General population – Hazard via oral route

Long term systemic oral DNEL, General population

The DNEL long term, systemic (oral) is derived by route-to route extrapolation from the repeated dose inhalation toxicity study.

 

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

The repeated dose toxicity study 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 inhalation NOAEC is 50 mg/m^3.

 

Step 2: Modification of the starting point:

No default factor for adsorption is applied as a higher oral adsorption compared to inhalation adsorption is considered not justified (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8).

 

Standard respiratory volume of the rat (sRVrat) for 24 hours: 1.15 m³/kg bw/d

Frequency of exposure in study: 7 days/week, 6 hours/day

Frequency of general population exposure: 7 days/week, 24 hours/day

 

inhalation NOAEC 50 mg/m^3 * 1.15 m³/kg bw/d * (6/24)= 14.375 mg/kg bw/day dermal NOAEL

 

Step 3: Use of assessment factors: 400

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 4

Remaining uncertainties AF: 1

 

In conclusion, long term systemic oral DNEL, general population = 0.0359375 mg/kg bw/day

 

Short term systemic oral DNEL, General population

The test material is classified for acute oral toxicity cat. 4, according to Regulation (EC) No 1272/2008 (CLP). The acute systemic DNEL (oral) is extrapolated from the long term DNEL with multiplication by factor of 3 (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). The long term systemic DNEL (oral) is derived from the repeated dose inhalation toxicity study.

For Steps 1-3 please refer to “Long term systemic oral DNEL, General population”

 

Step 4: extrapolation from the long term DNEL

A factor of 3 is used: long term DNEL*3= short term DNEL

0.0359375*3=0.1078125 mg/kg bw/day

In conclusion, short term systemic oral DNEL, general population = 0.1078125 mg/kg bw/day

 

 

General population – Hazard for the eyes

For exposure to the eyes a low hazard was identified, as the test substance is classified for eye irritation Cat.2 according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E).

 

 

References

(not included as endpoint study record)

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.

- ECHA (2014). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. November 2014.

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

- ECHA (2016). Guidance on information requirements and chemical safety assessment.Part E: Risk Characterisation, Version 3.0, May 2016.