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Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

11.1 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:

450 mg/kg bw/day

Modified dose descriptor starting point:

LOAEC

Value:

555.3 mg/m³

Explanation for the modification of the dose descriptor starting point:

Step 1: PoD: NOAEL = 450 mg/kg bw/day

Step 2: Modification of PoD:

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:

= 450 mg/kg bw/day x 0.5 x 1/0.38 m3/kg bw/day x (6.7 m3/10 m3) x 1.4

= 555.3 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:

4

Justification:

The exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

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:

The recommended AF for other interspecies differences is applied.

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 OECD TG 422 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

Justification:

Even though the point of departure for DNEL derivation origins from a structural analogue substances, the read-across approach is considered unremarkable and DNEL derivation is considered conservative. Thus, there are no remaining uncertainties on this approach.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high 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:

3.15 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:

450 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

630 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No repeated dose dermal toxicity study with the test item is available. Therefore, long-term dermal DNEL was derived by route-to-route extrapolation.

The NOAEL of 450 mg/kg bw/day derived from an OECD TG 422 study performed with a structural analogue substance was used as the Point of Departure.

Step 1: PoD: NOAEL = 450 mg/kg bw/day

Step 2: Modification into a correct starting point:

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

There are no relevant experimental data on repeated dermal exposure. A conservative approach is used assuming identical dermal and oral absorption values even though a low dermal absorption value can be expected due to the physico- chemical properties of the test item.

Corrected NOAEL (dermal) for workers:

450 mg/kg bw/day x 1.4

= 630 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:

4

Justification:

The exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

AF for interspecies differences (allometric scaling):

4

Justification:

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

AF for other interspecies differences:

2.5

Justification:

The exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

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 OECD TG 422 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

Justification:

Even though the point of departure for DNEL derivation origins from a structural analogue substances, the read-across approach is considered unremarkable and DNEL derivation is considered conservative. Thus, there are no remaining uncertainties on this approach.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

Systemic DNEL short-term and long-term:

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012).

Inhalation

Long term, systemic DNEL – exposure via inhalation (workers)

Using a conservative approach, a worker DNEL (long-term inhalation exposure) is calculated. This worker long-term DNEL is considered to ensure also an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected).

No repeated dose inhalation toxicity study with the test item is available. Therefore, long-term inhalation DNEL was derived by route-to-route extrapolation from an oral repeated dose toxicity study:

Based on an OECD TG 422 study with a structural analogue substance, daily oral administration to Wistar rats revealed no signs of systemic toxicity up to the highest dose tested i. e. 450 mg/kg bw/d. The NOAEL for systemic toxicity, was therefore considered to be 200 mg/kg bw/day. NOAEL for fertility and developmental toxicity was determined to be 200 and 450 mg/kg bw/d, respectively based on the conditions of this study. The NOAEL of systemic toxicity is applied as Point of Departure for DNEL derivation since it is considered to reflect worst case assumption. Findings observed at the highest dose level were associated with local irritation of the test item at the site of first contact (GIT). Therefore, a NOAEL for local effects was determined to be 200 mg/kg bw/d which corresponds to a concentration of 40 mg/mL. Since the registered substance is classified for skin corrosion and eye damage a high hazard is assumed for local effects.

Step 1: PoD: NOAEL = 450 mg/kg bw/day

Step 2: Modification of PoD:

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:

= 450 mg/kg bw/day x 0.5 x 1/0.38 m3/kg bw/day x (6.7 m3/10 m3) x 1.4

= 555.3 mg/m3

Step 3: Overall AF= 50

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: 4

The exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

Whole database AF: 1

The OECD TG 422 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 = 11.1 mg/m3

Acute, systemic DNEL- exposure via inhalation (workers)

There is no short-term or long-term toxicity study via inhalation route available for the test item. Due to its very low vapour pressure (< 1 Pa), high peak-inhalation exposure is not considered as relevant. The test item is unlikely to be available as a vapour to a large extent. Thus, the acute inhalation DNEL was not derived. Further, long-term DNELs are considered sufficient to ensure that acute effects do not occur. In addition, the test item is not classified as acutely toxic via inhalation or dermal route.

Dermal

Long term, systemic DNEL- exposure via dermal route (workers)

No repeated dose dermal toxicity study with the test item is available. Therefore, long-term dermal DNEL was derived by route-to-route extrapolation.

The NOAEL of 450 mg/kg bw/day derived from an OECD TG 422 study performed with a structural analogue substance was used as the Point of Departure.

Step 1: PoD: NOAEL = 450 mg/kg bw/day

Step 2: Modification into a correct starting point:

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

There are no relevant experimental data on repeated dermal exposure. A conservative approach is used assuming identical dermal and oral absorption values even though a low dermal absorption value can be expected due to the physico- chemical properties of the test item.

Corrected NOAEL (dermal) for workers:

= 450 mg/kg bw/day x 1.4

= 630 mg/kg bw/day

Step 3: Overall AF= 200

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

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

 

Interspecies AF, remaining differences: 2.5

The recommended AF for other interspecies differences is applied.

 

Intraspecies AF (worker): 5

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

 

Dose-response relationship AF: 1

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

 

Exposureduration AF: 4
The exposure duration of the OECD TG 422 study was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

In conclusion, long term systemic dermal DNEL, workers = 3.15 mg/kg bw/day

Acute, systemic DNEL- dermal exposure (workers)

The test item is not classified for acute dermal toxicity according to Regulation (EC) No 1272/2008 (CLP). Thus, the acute systemic dermal DNEL was not derived. Further, long-term DNELs are considered sufficient to ensure that acute effects do not occur. Moreover, the test item is classified as skin corrosive cat 1A according to CLP and protection measures to avoid local effects are considered sufficient to protect against systemic effects as well.

Local DNEL for inhalation and dermal route, short-term and long-term:

The test item is classified for skin and eye corrosion according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is conducted. Appropriate qualitative risk managements measures should be implemented to avoid exposure. The substance is assigned to the high hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.95 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):

100

Dose descriptor starting point:

NOAEL

Value:

450 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

195.6 mg/m³

Explanation for the modification of the dose descriptor starting point:

Step 1: PoD: NOAEL = 450 mg/kg bw/day

Step 2: Modification of PoD:

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

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

Corrected NOAEC (inhalation) for general population:

= 450 mg/kg bw/day x 0.5 x 1/1.15 m3/kg bw/day

= 195.6 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:

4

Justification:

The exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

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:

The recommended AF for other interspecies differences is applied.

AF for intraspecies differences:

10

Justification:

The default value for the heterogenous group "consumer" is used.

AF for the quality of the whole database:

1

Justification:

The OECD TG 422 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

Justification:

Even though the point of departure for DNEL derivation origins from a structural analogue substances, the read-across approach is considered unremarkable and DNEL derivation is considered conservative. Thus, there are no remaining uncertainties on this approach.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

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:

1.125 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):

400

Dose descriptor starting point:

NOAEL

Value:

450 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

450 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No repeated dose dermal toxicity study with the test item is available. Therefore, long-term dermal DNEL was derived by route-to-route extrapolation.

The NOAEL of 450 mg/kg bw/day derived from an OECD TG 422 study performed with the test item was used as the Point of Departure.

Step 1:PoD: NOAEL = 450 mg/kg bw/day

Step 2:Modification into a correct starting point:
Correction for difference between human and experimental exposure conditions: 7 d rat, 24 h/7 d, 24h general population = 1

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:

The exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

AF for interspecies differences (allometric scaling):

4

Justification:

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

AF for other interspecies differences:

2.5

Justification:

The exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

AF for intraspecies differences:

10

Justification:

The default value for the heterogenous group "consumer" is used.

AF for the quality of the whole database:

1

Justification:

The OECD TG 422 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

Justification:

Even though the point of departure for DNEL derivation origins from a structural analogue substances, the read-across approach is considered unremarkable and DNEL derivation is considered conservative. Thus, there are no remaining uncertainties on this approach.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.125 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):

400

Dose descriptor starting point:

NOAEL

Value:

450 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

450 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No modification of PoD needed.

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:

The exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

AF for interspecies differences (allometric scaling):

4

Justification:

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

AF for other interspecies differences:

2.5

Justification:

The exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

AF for intraspecies differences:

10

Justification:

The default value for the heterogenous group "consumer" is used.

AF for the quality of the whole database:

1

Justification:

The OECD TG 422 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

Justification:

Even though the point of departure for DNEL derivation origins from a structural analogue substances, the read-across approach is considered unremarkable and DNEL derivation is considered conservative. Thus, there are no remaining uncertainties on this approach.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - General Population

Systemic DNEL short-term and long-term:

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012).

Inhalation

Long term, systemic DNEL – exposure via inhalation (consumer)

Using a conservative approach, a consumer DNEL (long-term inhalation exposure) is calculated. This consumer long-term DNEL is considered to ensure also an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected).

No repeated dose inhalation toxicity study with the test item is available. Therefore, long-term inhalation DNEL was derived by route-to-route extrapolation from an oral repeated dose toxicity study:

Based on an OECD TG 422 study with the test item, daily oral administration to Wistar rats revealed no signs of systemic toxicity up to the highest dose tested i. e. 450 mg/kg bw/d. The NOAEL for systemic toxicity, was therefore considered to be 450 mg/kg bw/day. NOAEL for fertility and developmental toxicity was determined to be 200 and 450 mg/kg bw/d, respectively based on the conditions of this study. The NOAEL of systemic toxicity is applied as Point of Departure for DNEL derivation since it is considered to reflect worst case assumption. Findings observed at the highest dose level were associated with local irritation of the test item at the site of first contact (GIT). Therefore, a NOAEL for local effects was determined to be 200 mg/kg bw/d which corresponds to a concentration of 40 mg/mL. Since the registered substance is classified for skin corrosion and eye damage a high hazard is assumed for local effects.

Step 1:PoD: NOAEL = 450 mg/kg bw/day

Step 2:Modification of PoD:

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

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

Corrected NOAEC (inhalation) for general population:

= 450 mg/kg bw/day x 0.5 x 1/1.15 m3/kg bw/day

= 195.6 mg/m3

Step 3: Overall AF= 100

Intraspecies AF (consumer): 5

The default value for the heterogenous group "consumer" 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: 4

The exposure duration of the OECD TG 422 study performed with the test item was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

Whole database AF: 1

The OECD TG 422 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 = 5.55 mg/m3

Acute, systemic DNEL- exposure via inhalation (workers)

There is no short-term or long-term toxicity study via inhalation route available for the test item. Due to its very low vapour pressure (< 1 Pa), high peak-inhalation exposure is not considered as relevant. The test item is unlikely to be available as a vapour to a large extent. Thus, the acute inhalation DNEL was not derived. Further, long-term DNELs are considered sufficient to ensure that acute effects do not occur. In addition, the test item is not classified as acutely toxic via inhalation or dermal route.

Dermal

Long term, systemic DNEL- exposure via dermal route (consumer)

No repeated dose dermal toxicity study with the test item is available. Therefore, long-term dermal DNEL was derived by route-to-route extrapolation.

The NOAEL of 450 mg/kg bw/day derived from an OECD TG 422 study performed with the test item was used as the Point of Departure.

No repeated dose dermal toxicity study with the test item is available. Therefore, long-term dermal DNEL was derived by route-to-route extrapolation.

The NOAEL of 450 mg/kg bw/day derived from an OECD TG 422 study performed with the read-across substance was used as the Point of Departure.

Step 1: PoD: NOAEL = 450 mg/kg bw/day

Step 2: Modification into a correct starting point:
Correction for difference between human and experimental exposure conditions: 7 d rat, 24 h/7 d, 24h general population = 1

Step 3: Overall AF= 400

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

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

 

Interspecies AF, remaining differences: 2.5

The recommended AF for other interspecies differences is applied.

 

Intraspecies AF (consumer): 10

The default value for the heterogenous group "consumer" is used

 

Dose-response relationship AF: 1

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

 

Exposure duration AF: 4
The exposure duration of the OECD TG 422 study was up to 63 days for females and 29 days for males. In comparison to a subacute 28-day study the OECD TG 422 study provides additional information on fertility and developmental toxicity, which justifies the assessment factor of 4.

In conclusion, long term systemic dermal DNEL, consumers = 1.125 mg/kg bw/day

Acute, systemic DNEL- dermal exposure (consumer)

The test item is not classified for acute dermal toxicity according to Regulation (EC) No 1272/2008 (CLP). Thus, the acute systemic dermal DNEL was not derived. Further, long-term DNELs are considered sufficient to ensure that acute effects do not occur. Moreover, the test item is classified as skin corrosive cat 1A according to CLP and protection measures to avoid local effects are considered sufficient to protect against systemic effects as well.

Local DNEL for inhalation and dermal route, short-term and long-term:

The test item is classified for skin and eye corrosion according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is conducted. Appropriate qualitative risk managements measures should be implemented to avoid exposure. The substance is assigned to the high hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).