2-Butanone, peroxide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.52 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:

51 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

62.9 mg/m³

Explanation for the modification of the dose descriptor starting point:

Standard respiratory volume, human (sRVhuman) for 8 h per person (70 kg): 6.7 m³

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

Worker respiratory volume (wRV) for 8 hours with light physical activity per person: 10 m³

Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 1/2 (default)

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEC (inhalation) for workers:

NOAEC_corr = NOAEL_oral x 1/0.38 m³/kg bw/day x 6.7 m³/10m³ x 7d/5d x ABS_oral/ABS_inh

NOAEC_corr = 51 mg/kg bw/day x 0.5 x (1/0.38 m³/kg bw/day) x (6.7 m³/10 m³) x (7 days/ 5 days)

NOAEC_corr = 51 mg/kg bw/day x 0.5 x 2.63 x 0.67 m³ x 1.4

NOAEC_corr = 62.9 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:

2

Justification:

Extrapolation from subchronic to chronic exposure.

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:

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:

DNEL (Derived No Effect Level)

Value:

7.55 mg/m³

Most sensitive endpoint:

acute toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

DNEL extrapolated from long term DNEL

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):

100

Dose descriptor starting point:

NOAEL

Value:

51 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

142.8 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Using a conservative approach, a worker DNEL (long-term dermal exposure) is derived. Based on the physico-chemical properties of MEKP especially its high hydrophilicity (log Kow: 0.3 to 2.04 and water solubility: 6.5 g/L) dermal absorption is considered to be 50% of oral absorption.

 

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEL (dermal) for workers:

NOAEL_corr = NOAEL_oral x 7d/5d x ABS_oral/ABS_inh

NOAEL_corr = 51 mg/kg bw/day x 1.4 x 2

NOAEL_corr = 142.8 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:

2

Justification:

Extrapolation from subchronic to chronic exposure.

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:

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:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA (see references below).

 

Acute, systemic DNEL

The acute DNEL was calculated as 3 times the long-term DNEL, according to Guidance on information requirements and chemical safety assessment, chapter R.8: Characterisation of dose[concentration]-response for human health, November 2012.

Acute, systemic DNEL, inhalation: 7.55 mg/m³

Methyl-ethyl ketone peroxide (MEKP) is classified for acute oral and inhalation toxicity, cat. 4 according to Regulation (EC) No 1272/2008 (CLP). MEKP is not classified for systemic toxicity after acute inhalation and dermal exposure, according Regulation (EC) No 1272/2008 (CLP), based on the test data for acute dermal and inhalation toxicity. As workers are considered not to be exposed orally and no acute dermal hazard was identified, no acute worker DNEL for systemic effects after oral or dermal exposure is derived.

MEKP was further shown to have no skin sensitising potential. No qualitative assessment is required.

 

Acute/long term DNEL for local effects

Skin irritation/corrosion: 

MEKP is classified as skin corrosive, cat 1B, H314 according to Regulation (EC) No 1272/2008 (CLP) based on the available experimental data. Therefore, a qualitative assessment is conducted.

 

Eye irritation:

MEKP causes severe eye damage, cat 1, H318 according to Regulation (EC) No 1272/2008 (CLP) based on the available experimental data. Therefore, a qualitative assessment is conducted.

 

Respiratory irritation:

MEKP causes severe skin burns and eye damage and signs of respiratory irritation were also observed in acute inhalation toxicity studies available. Therefore a qualitative assessment is conducted.

 

Appropriate qualitative risk managements measures should be implemented to avoid exposure. The substance is assigned to the medium hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).

 

Long term, systemic DNEL

Occupational exposure to MEKP occurs mainly by dermal route, and may also occur by inhalation exposure. Therefore two long-term DNELs are calculated for workers.

 

Exposure by inhalation

 

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

An EOGRTS according to OECD TG 443 (2021) 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 in rats is 51 mg/kg bw/day.

 

Step 2: Modification into a correct starting point:

Using a conservative approach, a worker DNEL (long-term inhalation exposure) is derived.

Relevant dose descriptor (NOAEL): 51 mg/kg bw/day

 

Standard respiratory volume, human (sRVhuman) for 8 h per person (70 kg): 6.7 m³

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

Worker respiratory volume (wRV) for 8 hours with light physical activity per person: 10 m³

Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 1/2 (default)

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEC (inhalation) for workers:

NOAEC_corr = NOAEL_oral x 1/0.38 m³/kg bw/day x 6.7 m³/10m³ x 7d/5d x ABS_oral/ABS_inh

NOAEC_corr = 51 mg/kg bw/day x 0.5 x (1/0.38 m³/kg bw/day) x (6.7 m³/10 m³) x (7 days/ 5 days)

NOAEC_corr = 51 mg/kg bw/day x 0.5 x 2.63 x 0.67 m³ x 1.4

NOAEC_corr = 62.9 mg/m³

 

Step 3: Use of assessment factors: 25

Intraspecies AF (worker): 5

The default value for the relatively homogenous group "worker" is used.

Interspecies AF, remaining differences: 2.5

The recommended AF for other interspecies differences is applied.

Allometric scaling AF: 1

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).

Dose response relationship AF: 1

The dose response relationship is considered unremarkable, therefore no additional factor is used.

Exposure duration AF: 2

Extrapolation from subchronic to chronic exposure.

Whole database AF: 1

The OECD TG 443 toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties: 1
DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied. 

In conclusion, long term systemic inhalation DNEL, workers = 2.52 mg/m3

 

Dermal exposure 

 

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

An EOGRTS according to OECD TG 443 (2021) 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 in rats is 51 mg/kg bw/day.

 

Step 2: Modification of the starting point:

Using a conservative approach, a worker DNEL (long-term dermal exposure) is derived. Based on the physico-chemical properties of MEKP especially its high hydrophilicity (log Kow: 0.3 to 2.04 and water solubility: 6.5 g/L) dermal absorption is considered to be 50% of oral absorption.

 

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEL (dermal) for workers:

NOAEL_corr = NOAEL_oral x 7d/5d x ABS_oral/ABS_inh

NOAEL_corr = 51 mg/kg bw/day x 1.4 x 2

NOAEL_corr = 142.8 mg/kg bw/day

 

Step 3: Use of assessment factors: 100

Intraspecies AF (worker): 5

The default value for the relatively homogenous group "worker" is used.

Interspecies AF, remaining differences: 2.5

The recommended AF for other interspecies differences is applied.

Allometric scaling AF: 4

The default allometric scaling factor for the differences between rats and humans is applied.

Dose response relationship AF: 1

The dose response relationship is considered unremarkable, therefore no additional factor is used.

Exposure duration AF: 2

Extrapolation from subchronic to chronic exposure.

Whole database AF: 1

The OECD 443 study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties: 1

DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.

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

 

 

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.

- ECHA (2014). Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance, Guidance on Toxicokinetics.

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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.44 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):

50

Dose descriptor starting point:

NOAEL

Value:

51 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

22.17 mg/m³

Explanation for the modification of the dose descriptor starting point:

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

Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 1/2 (default)

Corrected NOAEC (inhalation) for general population:

NOAEC_corr = NOAEL_oral x 1/1.15 m³/kg bw/day x ABS_oral/ABS_inh

NOAEC_corr = 51 mg/kg bw/day x 0.87 x 0.5

NOAEC_corr= 22.17 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:

2

Justification:

Extrapolation from subchronic to chronic exposure.

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:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

10

Justification:

The default value for the more heterogenous 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)

Most sensitive endpoint:

irritation (respiratory tract)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.51 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):

200

Dose descriptor starting point:

NOAEL

Value:

51 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

102 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Using a conservative approach, a general population DNEL (long-term dermal exposure) is derived. Based on the physico-chemical properties of MEKP especially its high hydrophilicity (log Kow: 0.3 to 2.04 and water solubility: 6.5 g/L) dermal absorption is considered to be 50% of oral absorption.

NOAEL_corr = NOAEL_oral x ABS_oral/ABS_inh

NOAEL_corr = 51 mg/kg bw/day * 2

NOAEL_corr =  102 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:

2

Justification:

Extrapolation from subchronic to chronic exposure.

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 more heterogenous 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

Most sensitive endpoint:

acute toxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.26 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):

200

Dose descriptor starting point:

NOAEL

Value:

51 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

51 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No modification is needed as the same route of exposure is assessed and the same exposure period is assumed.

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:

Extrapolation from subchronic to chronic exposure.

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 more heterogenous 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 for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA (see references below).

 

Acute, systemic DNEL

Although MEKP is classified for acute oral and inhalation toxicity according to Regulation (EC) No 1272/2008, general population is intended to be exposed to peak concentrations neither via dermal, inhalation nor oral route. Therefore, no DNEL (short-term, inhalative, dermal and oral exposure) is derived for general population.  

MEKP was further shown to have no skin sensitisation potential. No qualitative assessment is required.

 

Acute/long term DNEL for local effects

Skin irritation/corrosion: 

MEKP is classified as skin corrosive, cat 1B, H314 according to Regulation (EC) No 1272/2008 (CLP) based on the available experimental data. Therefore, a qualitative assessment is conducted.

 

Eye irritation:

MEKP causes severe eye damage, cat 1, H318 according to Regulation (EC) No 1272/2008 (CLP) based on the available experimental data. Therefore, a qualitative assessment is conducted.

 

Respiratory irritation:

MEKP causes severe skin burns and eye damage and signs of respiratory irritation were also observed in acute inhalation toxicity studies available. Therefore a qualitative assessment is conducted.

 

Appropriate qualitative risk managements measures should be implemented to avoid exposure. The substance is assigned to the medium hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).

 

Long term, systemic DNEL

Everyday life exposure to MEKP occurs mainly by dermal route, and may also occur by inhalation and oral exposure. Therefore three long-term DNELs are calculated for the general population.

 

 

Exposure by inhalation

 

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

An EOGRTS according to OECD TG 443 (2021) 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 in rats is 51 mg/kg bw/day.

 

Step 2: Modification into a correct starting point:

Using a conservative approach, a general population DNEL (long-term inhalation exposure) is derived.

Relevant dose descriptor (NOAEL): 51 mg/kg bw/day

 

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

Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 1/2 (default)

Corrected NOAEC (inhalation) for general population:

NOAEC_corr = NOAEL_oral x 1/1.15 m³/kg bw/day x ABS_oral/ABS_inh

NOAEC_corr = 51 mg/kg bw/day x 0.87 x 0.5

NOAEC_corr = 22.17 mg/m³

 

Step 3: Use of assessment factors: 50

Intraspecies AF (general population): 10

The default value for the relatively heterogenous group "general population" is used.

Interspecies AF, remaining differences: 2.5

The recommended AF for other interspecies differences is applied.

Allometric scaling AF: 1

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).

Dose response relationship AF: 1

The dose response relationship is considered unremarkable, therefore no additional factor is used.

Exposure duration AF: 2

Extrapolation from subchronic to chronic exposure.

Whole database AF: 1

The OECD TG 443 toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties: 1
DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied. 

In conclusion, long term systemic inhalation DNEL, general population = 0.44 mg/m3

 

 

Dermal exposure 

 

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

An EOGRTS according to OECD TG 443 (2021) 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 in rats is 51 mg/kg bw/day.

 

Step 2: Modification of the starting point:

Using a conservative approach, a general population DNEL (long-term dermal exposure) is derived. Based on the physico-chemical properties of MEKP especially its high hydrophilicity (log Kow: 0.3 to 2.04 and water solubility: 6.5 g/L) dermal absorption is considered to be 50% of oral absorption.

 

NOAEL_corr = NOAEL_oral x x ABS_oral/ABS_inh

NOAEL_corr = 51 mg/kg bw/day * 2

NOAEL_corr =  102 mg/kg bw/day

 

Step 3: Use of assessment factors: 200

Intraspecies AF (general population): 10

The default value for the relatively heterogenous group "general population" is used.

Interspecies AF, remaining differences: 2.5

The recommended AF for other interspecies differences is applied.

Allometric scaling AF: 4

The default allometric scaling factor for the differences between rats and humans is applied.

Dose response relationship AF: 1

The dose response relationship is considered unremarkable, therefore no additional factor is used.

Exposure duration AF: 2

Extrapolation from subchronic to chronic exposure.

Whole database AF: 1

The study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties: 1

DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.

In conclusion, long term systemic dermal DNEL, general population = 0.51 mg/kg bw/day

 

 

Oral exposure

Although MEKP has no bioaccumulation potential and no risk assessment for secondary poisoning is required an oral DNEL (long term, systemic) for the general population is derived.

 

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

An EOGRTS according to OECD TG 443 (2021) 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 in rats is 51 mg/kg bw/day.

 

Step 2: Modification of the starting point:

No corrections must be made. The PoD is 51 mg/kg bw/day

 

Step 3: Use of assessment factors: 200

Intraspecies AF (general population): 10

The default value for the relatively heterogenous group "general population" is used.

Interspecies AF, remaining differences: 2.5

The recommended AF for other interspecies differences is applied.

Allometric scaling AF: 4

The default allometric scaling factor for the differences between rats and humans is applied.

Dose response relationship AF: 1

The dose response relationship is considered unremarkable, therefore no additional factor is used.

Exposure duration AF: 2

Extrapolation from subchronic to chronic exposure.

Whole database AF: 1

The study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties: 1
DNEL Derivation is considered conservative, reflecting reasonable worst case assumptions. Therefore, no further AF for remaining uncertainties is applied.

In conclusion, long term systemic oral DNEL, general population = 0.26 mg/kg bw/day

 

 

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.

- ECHA (2014). Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance, Guidance on Toxicokinetics.

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