Dodecanoic acid, 3-[[3-[[[2,2-dimethyl-3-[(1-oxododecyl)oxy]propylidene]amino]methyl]-3,5,5-trimethylcyclohexyl]imino]-2,2-dimethylpropyl ester

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10.5 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

Modified dose descriptor starting point:

NOAEC

Value:

262.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. A conservative approach is used assuming a two times higher absorption via the inhalation route (end route) as compared to the oral route (starting route).

AF for dose response relationship:

1

Justification:

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

AF for differences in duration of exposure:

2

Justification:

The recommended time extrapolation factor for a subchronic toxicity study is used.

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed.

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:

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:

30 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

Modified dose descriptor starting point:

NOAEL

Value:

3 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. Taken into account the physico-chemical properties of the substance, dermal absoption is anticipated to be low (10 % of oral absorption). For details 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 recommended time extrapolation factor for a subchronic toxicity study is used.

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

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

42 µg/cm²

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor:

other: EC3 of 8.4 % (equivalent to 2100 µg/cm2)

AF for dose response relationship:

1

Justification:

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

AF for differences in duration of exposure:

1

Justification:

No time extrapolation factor is needed.

AF for interspecies differences (allometric scaling):

1

Justification:

The recommended asessment factor for interspecies variation is already applied (see AF for other interspecies differences).

AF for other interspecies differences:

10

Justification:

Recommended assessment factor for interspecies variation.

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:

42 µg/cm²

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

other: EC3 of 8.4 % (equivalent to 2100 µg/cm2)

AF for dose response relationship:

1

Justification:

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

AF for interspecies differences (allometric scaling):

1

Justification:

No time extrapolation factor is needed.

AF for other interspecies differences:

10

Justification:

Recommended assessment factor for interspecies variation.

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.

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

General

DNEL derivation for the substance SIKA Hardener LI 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

Calculation of dose descriptor

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

For risk characterisation a inhalation NOAEC was derived by route to route extrapolation.

The oral NOAEL of 300 mg/kg bw/day, obtained from chronic repeated dose toxicity testing in rats was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

Step 2: Modification into a correct starting point:

In a first step the oral NOAEL was transferred to humans with a factor of 4 for allometric scaling from rats. For worker a NOEC long-term, inhalation was calculated assuming 70 kg per person, 8h light activity (10 m³ breathing volume), 50 % absorption via oral routes and 100 % absorption via inhalatory routes. NOEC (Worker) inhalation = 300 mg/kg bw/day * 1/4 *70 kg * 1/10 m³ * 50% Abs, (oral) / 100 % Abs, (inhal) = 262.5 mg/m³

Step 3: Use of assessment factors: 25

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

time extrapolation AF: 2

In conclusion the long term systemic inhalation DNEL workers was calculated to be 10.5 mg/m³ bw/day.

Short term acute inhalation DNEL, worker

Based on the uses of the substance, exposure is not expected (see section 3.5). Furthermore, the test material is not classified and labelled for acute dermal and oral toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Thus, in accordance with “Guidance on information requirements and chemical safety assessment chapter R8: Characterisation of dose (concentration)- response for human health” no DNEL is required.

Workers – Hazard via dermal route

Long term systemic dermal DNEL, worker

Calculation of dose descriptor

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

For risk characterisation a dermal NOAEL was derived by route to route extrapolation.

The oral NOAEL of 300 mg/kg bw/day, obtained from chronic repeated dose oral toxicity testing in rats, was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

Step 2: Modification into a correct starting point:

Based on the physical chemical properties of the substance (water solubility <1 mg/L, log Pow value 7.41) dermal uptake of the substance is assumed to be low. According to “Guidance on information requirements and chemical safety assessment chapter R7c: Endpoint specific Guidance”, an absorption rate of 10 % through skin can be deduced as the molecular mass is above 500 and log P is outside the range [-1, 4]. In conclusion, dermal NOAEL = oral NOAEL x [ABS oral rat/ABS dermal human] = 300 mg/kg bw/day x (100/10) = 3000 mg/kg bw/d. 

Step 3: Use of assessment factors: 50

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF (chronic exposure period): 1

In conclusion the long term systemic dermal DNEL workers were calculated to be 60 mg/kg bw/day.

Local effects, long term dermal exposure

Data form the hydrolysis product 2,2-Dimethyl-3-lauroyloxy-propanal also reveals no local irritating effects to skin and eye. The second hydrolysis product 3-aminomethyl-3,5,5-trimethylcyclohexylamine is classified as skin corrosive. Exposure to this hydrolysis product can however be excluded based on information from the substance use (for details refer to section 3.5 or CSR). Only repeated exposure to the substance causes skin sensitisation. Thus, local dermal effects are covered by the long term local risk assessment and no quantitative acute local dermal assessment is required.

Based on the available toxicological information, SIKA Hardener LI is not subject to classification for skin, eye and/or respiratory irritation, but is classified as skin sensitising cat. 1B. Thus, a quantitative risk assessment is done. The DNEL sensitisation is derived from an extrapolated EC3 value from a LLNA assay of 8.4 %. The EC3 value of 8.4 % is equivalent to 2100 µg/cm2 (Calculated using the formula EC3 [%]*250 [μg/cm2/% ] = EC3 [μg/cm2], Guidance on information requirements and chemical safety assessment, Chapter R.8).

With an EC3 of 1000-10000 µg/cm2 SIKA Hardener LI is classified as weak sensitizer according to Geberick et al.(2001). According to Griem et al. (2003) and taking into account the weak sensitizing potential an assessment factor of 1 was applied. No matrix effect is expected and no adjustment with regard to the use is necessary (based on the fact that the amine becomes part of a polymer immediately after release, a factor of >1 is not justified). According to ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health" an assessment factor of 10 for interspecies differences and a factor of 5 for worker intraspecies differences was applied, resulting in a total factor of 50. In conclusion, a DNEL sensitisation of 42 µg/cm2 was derived.

References:

Geberick et al. (2001). Contact Dermatitis, 45,333-340

Griem et al. (2003). Regulatory Toxicology and Pharmacology, 38, 269-290.

 

Acute short term dermal DNEL, worker

Local dermal effects are covered by the long term local risk assessment and no quantitative acute local dermal assessment is required.

Worker – Hazard for the eyes

According to the EU (DSD and GHS) criteria for classification and labelling requirements for dangerous substances and preparations the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.

 

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 (2012). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. November 2012.

- 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:

2.25 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

Modified dose descriptor starting point:

NOAEC

Value:

112.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. A conservative approach is used assuming a two times higher absorption via the inhalation route (end route) as compared to the oral route (starting route).

AF for dose response relationship:

1

Justification:

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

AF for differences in duration of exposure:

2

Justification:

The recommended time extrapolation factor for a subchronic toxicity study is used.

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 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:

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:

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

Modified dose descriptor starting point:

NOAEL

Value:

3 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. Taken into account the physico-chemical properties of the substance, dermal absoption is anticipated to be low (10 % of oral absorption). For details 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 recommended time extrapolation factor for a subchronic toxicity study is used.

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:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

21 mg/cm²

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor:

other: EC3 of 8.4 % (equivalent to 2100 µg/cm2)

AF for dose response relationship:

1

Justification:

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

AF for differences in duration of exposure:

1

Justification:

No time extrapolation factor is needed.

AF for interspecies differences (allometric scaling):

1

Justification:

The recommended assessment factor for interspecies variation is already applied (see AF for other interspecies differences).

AF for other interspecies differences:

10

Justification:

Recommended assessment factor for interspecies variation.

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:

21 mg/cm²

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

other: EC3 of 8.4 % (equivalent to 2100 µg/cm2)

AF for dose response relationship:

1

Justification:

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

AF for interspecies differences (allometric scaling):

1

Justification:

The recommended assessment factor for interspecies variation is already applied (see AF for other interspecies differences).

AF for other interspecies differences:

10

Justification:

Recommended assessment factor for interspecies variation.

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:

he approach used for DNEL derivation is conservative. No further assessment factors are required.

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.5 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

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation is required.

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 recommended time extrapolation factor for a subchronic toxicity study is used.

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:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

General

DNEL derivation for the substance SIKA Hardenr LI 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

Calculation of dose descriptor

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

For risk characterisation a inhalation NOAEC was derived by route to route extrapolation.

The oral NOAEL of 300 mg/kg bw/day, obtained from chronic repeated dose toxicity testing in rats was considered as key value for the chemical safety assessment and therefore the most relevant starting point.

Step 2: Modification into a correct starting point:

In a first step the oral NOAEL was transferred to humans with a factor of 4 for allometric scaling from rats. For general population a NOEC long-term, inhalation was calculated assuming 60 kg per person, 24h light activity (20 m³ breathing volume), 50 % absorption via oral routes and 100 % absorption via inhalatory routes.

NOEC (General population) inhalation = 300 mg/kg bw/day * 1/4 *60 kg * 1/20 m³ * 50%Abs, (oral) / 100 % Abs, (inhal) = 112.5 mg/m³

Step 3: Use of assessment factors: 50

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 2 (subchronic study)

In conclusion, long term systemic inhalation DNEL, general population = 2.25 mg/m3

Short term acute inhalation DNEL, general population

The test material is not classified and labelled for acute oral and dermal toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Thus, in accordance with “Guidance on information requirements and chemical safety assessment chapter R8: Characterisation of dose (concentration)- response for human health” no DNEL is required.

Local effects

No data on respiratory irritation is available. As the substance is not classified as skin and eye irritating also no adverse effects on respiratory system is expected (in accordance with "Guidance on information requirements and chemical safety assessment, chapter R8"). Additionally, based on the uses of the substance (see section 3.5), exposure to the substance and its hydrolysis products is not expected. Thus, no DNEL is required.

General population – Hazard via dermal route

Long term systemic dermal DNEL, general population

Calculation of dose descriptor

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

For risk characterisation a dermal NOAEL was derived by route to route extrapolation.

The oral NOAEL of 300 mg/kg bw/day, obtained from chronic repeated dose oral toxicity testing in rats, was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

Step 2: Modification into a correct starting point:

Based on the physical chemical properties of the substance (water solubility <1 mg/L, log Pow value 7.41) dermal uptake of the substance is assumed to be low. According to “Guidance on information requirements and chemical safety assessment chapter R7c: Endpoint specific Guidance”, an absorption rate of 10 % through skin can be deduced as the molecular mass is above 500 and log P is outside the range [-1, 4].

In conclusion, dermal NOAEL = oral NOAEL x [ABS oral rat/ABS dermal human] = 300 mg/kg bw/day x (100/10) = 3000 mg/kg bw/d.

Step 3: Use of assessment factors: 200

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 2 (subchronic study)

In conclusion, long term systemic dermal DNEL, general population = 15 mg/kg bw/day

Local effects, long term dermal exposure

Data from the hydrolysis product 2,2-Dimethyl-3-lauroyloxy-propanal also reveals no local irritating effects to skin and eye. The second hydrolysis product 3-aminomethyl-3,5,5-trimethylcyclohexylamine is classified as skin corrosive. Exposure to this hydrolysis product can however be excluded based on information from the substance use (for details refer to section 3.5 or CSR). Only repeated exposure to the substance causes skin sensitisation. Thus, local dermal effects are covered by the long term local risk assessment and no quantitative acute local dermal assessment is required.

Based on the available toxicological information, SIKA Hardener LI is not subject to classification for skin, eye and/or respiratory irritation, but is classified as skin sensitising cat. 1B. Thus, a quantitative risk assessment is done. The DNEL sensitisation is derived from an extrapolated EC3 value from a LLNA assay of 8.4 %. The EC3 value of 8.4 % is equivalent to 2100 µg/cm2 (Calculated using the formula EC3 [%]*250 [μg/cm2/% ] = EC3 [μg/cm2], Guidance on information requirements and chemical safety assessment, Chapter R.8). With an EC3 of 1000-10000 µg/cm2 SIKA Hardener LI is classified as weak sensitizer according to Geberick et al.(2001). According to Griem et al. (2003) and taking into account the weak sensitizing potential an assessment factor of 1 was applied. No matrix effect is expected and no adjustment with regard to the use is necessary (based on the fact that the amine becomes part of a polymer immediately after release, a factor of >1 is not justified). According to ECHA document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health" an assessment factor of 10 for interspecies differences and a factor of 10 for general population intraspecies differences was applied, resulting in a total factor of 100. In conclusion, a DNEL sensitisation of 21 µg/cm2 was derived.

References:

Geberick et al. (2001). Contact Dermatitis, 45,333-340

Griem et al. (2003). Regulatory Toxicology and Pharmacology, 38, 269-290.

Acute short term dermal DNEL, general population

Local dermal effects are covered by the long term local risk assessment and no quantitative acute local dermal assessment is required.

General population – Hazard for the eyes

According to the EU (DSD and GHS) criteria for classification and labelling requirements for dangerous substances and preparations the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.

General population – Hazard via oral route

Long term systemic oral DNEL, general population

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

A chronic study in rats 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 300 mg/kg bw/day.

Step 2: Modification of the starting point:

Not required.

Step 3: Use of assessment factors: 200

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 2 (subchronic study)

In conclusion, long term systemic oral DNEL, general population = 1.5 mg/kg bw/day

Acute short term dermal DNEL, general population

The acute oral systemic DNEL is not required as the substance is not classified for acute oral toxicity.

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 (2012). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. November 2012.

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