Sodium dibutyldithiocarbamate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.8 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:

16 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

19.75 mg/m³

Explanation for the modification of the dose descriptor starting point:

The substance fulfils the REACH Annex VII to Annex XI information requirements in accordance with ECHA guidance R7.5-7.7 (2017) for assessing long-term systemic toxicity. Since no repeated dose inhalation study is available, route-to-route extrapolation from the oral exposure route is performed. A NOAEL from a 90-day oral study performed with the structural analogue SDMC in the rat was used. A NOAEL of 10 mg/kg bw/day (males / females) was established in this study based on, haemolysis and haemosiderosis in spleen and kidney. Applying a correction for molecular weight, this results in a NOAEL of 10 x (227/143) = 16 mg/kg bw/day.

 

This oral rat NOAEL is converted to an inhalation NOAEC for rats by using a default respiratory volume for the rat corresponding to 8 hours (0.38 m3/kg bw). An oral absorption of 50% and inhalation absorption of 100% were used as default values. The resulting rat inhalation NOAEC is converted into inhalation worker NOAEC by correction for respiratory rate based on activity (6.7 m3 for normal light activity versus 10 m3 for worker activity) and by correction for 5 day exposure (7 days exposure per week in the study versus 5 days per week for workers):

16 * (1/0.38) * (50/100) * (6.7/10) * (7/5) = 19.75 mg/m3

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor of 1 is used (ECHA Guidance, Chapter R.8).

AF for differences in duration of exposure:

2

Justification:

A factor of 2 is dictated from a 90-day study to chronic toxicity (ECHA Guidance, Chapter R.8).

AF for interspecies differences (allometric scaling):

1

Justification:

As long as route-to-route extrapolation is not needed, allometric scaling should not be applied in cases where the dose unit (original or transformed) in experimental animal studies are expressed as concentrations (e.g. in mg/m³ air, ppm in diet, or mg/L in the drinking water) as these are assumed to be already scaled according to the allometric principle, since ventilation rate and food intake directly depend on the basal metabolic rate (ECHA, Guidance, Chapter R.8). In this case, route-to-route extrapolation is performed from an oral feeding study. The derived NOAEL is modified according to allometric principles to a NOAEC (mg/m³), therefore additional assessment factor for allometric scaling is not needed.

AF for other interspecies differences:

2.5

Justification:

Interspecies differences result from variation in the sensitivity of species due to differences in toxicokinetics and toxicodynamics. Some of the toxicokinetic differences can be explained by differences in body size (and related differences in basal metabolic rate). As no substance-specific data are available, the standard procedure for threshold effects is followed. As a default, an additional factor of 2.5 for interspecies differences (other than allometric scaling), i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part) is applied (ECHA Guidance, Chapter R.8).

AF for intraspecies differences:

5

Justification:

Intraspecies differences in human result from a multitude of biological factors such as genetic polymorphism affecting e.g. toxicokinetics/metabolism, age, gender, health status and nutritional status. For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill (ECHA Guidance, Chapter R.8).

AF for the quality of the whole database:

1

Justification:

The evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended (ECHA Guidance, Chapter R.8).

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, is recommended (ECHA Guidance, Chapter R.8).

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.24 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:

16 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

224 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Since no repeated dose dermal study is available, route-to-route extrapolation from the oral exposure route is performed. A NOAEL from a 90-day oral study performed with the structural analogue SDMC in the rat was used. A NOAEL of 10 mg/kg bw/day (males / females) was established in this study based on, haemolysis and haemosiderosis in spleen and kidney. Applying a correction for molecular weight, this results in a NOAEL of 10 x (227/143) = 16 mg/kg bw/day.

This oral NOAEL is converted to a dermal NOAEL for rats by correcting for differences in absorption between routes. An absorption value of 5% was considered to represent a sufficient worst-case approach. An oral absorption of 50% was used as default value. A correction for 5 day exposure (7 days exposure per week in the study versus 5 days per week for workers) was applied.

16 * (50/5) * (7/5) = 224 mg/kg bw/d

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor of 1 is used.

AF for differences in duration of exposure:

2

Justification:

A factor of 2 is dictated from a 90-day study to chronic toxicity (ECHA Guidance, Chapter R.8).

AF for interspecies differences (allometric scaling):

4

Justification:

Differences in metabolic rate (allometric scaling) should be accounted for by extrapolation of doses according to an overall assumption that equitoxic doses (when expressed in mg/kg bw/day) scale with body weight to the power of 0.75. This results in different default allometric scaling factors for the different animal species when compared with humans. For rats, the default assessment factor is 4 (ECHA Guidance, Chapter R.8).

AF for other interspecies differences:

2.5

Justification:

Interspecies differences result from variation in the sensitivity of species due to differences in toxicokinetics and toxicodynamics. Some of the toxicokinetic differences can be explained by differences in body size (and related differences in basal metabolic rate). As no substance-specific data are available, the standard procedure for threshold effects is followed. As a default, an additional factor of 2.5 for interspecies differences (other than allometric scaling), i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part) is applied (ECHA Guidance, Chapter R.8).

AF for intraspecies differences:

5

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment R.8, intraspecies differences in human result from a multitude of biological factors such as genetic polymorphism affecting e.g. toxicokinetics/metabolism, age, gender, health status and nutritional status. For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill.

AF for the quality of the whole database:

1

Justification:

The evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended (ECHA Guidance, Chapter R.8).

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, is recommended (ECHA Guidance, Chapter R.8).

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

233 µg/cm²

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

15

Dose descriptor:

other: EC3

AF for dose response relationship:

3

Justification:

The starting point for the DNEL calculation is a LOAEC, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor of 3 is used (ECHA Guidance, Chapter R.8).

AF for differences in duration of exposure:

1

Justification:

Repeated exposure is taken into account in the exposure assessment by using events/day.

AF for interspecies differences (allometric scaling):

1

Justification:

An assessment factor for allometric scaling is not needed since local effects are independent of the basal metabolic rate; allometric scaling should not be applied (ECHA, Guidance, Chapter R.8).

AF for other interspecies differences:

1

Justification:

The assessment factor for remaining uncertainties can be 1. For vehicle effects: an assessment factor of 1 is applied as the matrices of the products compiled from the substance are not intended to enhance penetration. For type of skin (skin thickness and skin integrity) it can be seen that the human skin (exposed hands) to be similarly or less sensitive compared to the skin of the mouse ear. The LLNA is selected as a model because the mouse ear is considered very thin with high blood flow and as such reflect a similar thickness and integrity compared to human skin in general

AF for intraspecies differences:

5

Justification:

Intraspecies differences in human result from a multitude of biological factors such as genetic polymorphism affecting e.g. toxicokinetics/metabolism, age, gender, health status and nutritional status. For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill (ECHA Guidance, Chapter R.8).

AF for the quality of the whole database:

1

Justification:

The evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended (ECHA Guidance, Chapter R.8).

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, is recommended (ECHA Guidance, Chapter R.8).

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)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.14 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:

16 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

6.96 mg/m³

Explanation for the modification of the dose descriptor starting point:

 Since no repeated dose inhalation study is available, route-to-route extrapolation from the oral exposure route is performed. A NOAEL from a 90-day oral study in the rat was used performed with the structural analogue SDMC. A NOAEL of 10 mg/kg bw/day (males / females) was established in this study based on, haemolysis and haemosiderosis in spleen and kidney. Applying a correction for molecular weight, this results in a NOAEL of 10 x (227/143) = 16 mg/kg bw/day. This oral rat NOAEL is converted to an inhalation NOAEC for rats by using a default respiratory volume for the rat corresponding to 24 hours (1.15 m3/kg bw).

16 * (1/1.15) * (50/100) = 6.96 mg/m3.

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor of 1 is used (ECHA Guidance, Chapter R.8).

AF for differences in duration of exposure:

2

Justification:

A factor of 2 is dictated from a 90-day study to chronic toxicity (ECHA Guidance, Chapter R.8).

AF for interspecies differences (allometric scaling):

1

Justification:

As long as route-to-route extrapolation is not needed, allometric scaling should not be applied in cases where the dose unit (original or transformed) in experimental animal studies are expressed as concentrations (e.g. in mg/m³ air, ppm in diet, or mg/L in the drinking water) as these are assumed to be already scaled according to the allometric principle, since ventilation rate and food intake directly depend on the basal metabolic rate (ECHA Guidance, Chapter R.8). In this case, route-to-route extrapolation is performed from an oral feeding study. The derived NOAEL is modified according to allometric principles to a NOAEC (mg/m³), therefore additional assessment factor for allometric scaling is not needed.

AF for other interspecies differences:

2.5

Justification:

Interspecies differences result from variation in the sensitivity of species due to differences in toxicokinetics and toxicodynamics. Some of the toxicokinetic differences can be explained by differences in body size (and related differences in basal metabolic rate). As no substance-specific data are available, the standard procedure for threshold effects is followed. As a default, an additional factor of 2.5 for interspecies differences (other than allometric scaling), i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part) is applied (ECHA Guidance, Chapter R.8).

AF for intraspecies differences:

10

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, intraspecies differences in human result from a multitude of biological factors such as genetic polymorphism affecting e.g. toxicokinetics/metabolism, age, gender, health status and nutritional status. It is usually assumed that a default assessment factor of 10 for the general population is sufficient to protect the larger part of the population, including e.g. children and the elderly. For threshold effects, this factor of 10 is the standard procedure, as a default, when assessing exposure to the general population.

AF for the quality of the whole database:

1

Justification:

The evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended(ECHA Guidance, Chapter R.8).

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, is recommended (ECHA Guidance, Chapter R.8).

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:

0.8 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:

16 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

160 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Since no repeated dose dermal study is available, route-to-route extrapolation from the oral exposure route is performed. A NOAEL from a 90-day oral study performed with the structural analogue SDMC in the rat was used. A NOAEL of 10 mg/kg bw/day (males / females) was established in this study based on, haemolysis and haemosiderosis in spleen and kidney. Applying a correction for molecular weight, this results in a NOAEL of 10 x (227/143) = 16 mg/kg bw/day.

This oral NOAEL is converted to a dermal NOAEL for rats by correcting for differences in absorption between routes. An absorption value of 5% was considered to represent a sufficient worst-case approach. An oral absorption of 50% was used as default value.

16 * (50/5) = 160 mg/kg bw/d

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor of 1 is used (ECHA Guidance, Chapter R.8).

AF for differences in duration of exposure:

2

Justification:

A factor of 2 is dictated from a 90-day study to chronic toxicity (ECHA Guidance, Chapter R.8).

AF for interspecies differences (allometric scaling):

4

Justification:

Differences in metabolic rate (allometric scaling) should be accounted for by extrapolation of doses according to an overall assumption that equitoxic doses (when expressed in mg/kg bw/day) scale with body weight to the power of 0.75. This results in different default allometric scaling factors for the different animal species when compared with humans. For rats, the default assessment factor is 4 (ECHA Guidance, Chapter R.8).

AF for other interspecies differences:

2.5

Justification:

Interspecies differences result from variation in the sensitivity of species due to differences in toxicokinetics and toxicodynamics. Some of the toxicokinetic differences can be explained by differences in body size (and related differences in basal metabolic rate). As no substance-specific data are available, the standard procedure for threshold effects is followed. As a default, an additional factor of 2.5 for interspecies differences (other than allometric scaling), i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part) is applied (ECHA Guidance, Chapter R.8).

AF for intraspecies differences:

10

Justification:

Intraspecies differences in human result from a multitude of biological factors such as genetic polymorphism affecting e.g. toxicokinetics/metabolism, age, gender, health status and nutritional status. For the general population, as standard procedure for threshold effects a default assessment factor of 10 is to be used, based on the fact that the all sub-populations are covered in this population: the very young, the very old, and the very ill (ECHA Guidance, Chapter R.8).

AF for the quality of the whole database:

1

Justification:

The evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended (ECHA Guidance, Chapter R.8).

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, is recommended (ECHA Guidance, Chapter R.8).

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

117 µg/cm²

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

30

Dose descriptor:

other: EC3

AF for dose response relationship:

3

Justification:

The starting point for the DNEL calculation is a LOAEC, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor of 3 is used (ECHA Guidance, Chapter R.8).

AF for differences in duration of exposure:

1

Justification:

Repeated exposure is taken into account in the exposure assessment by using events/day.

AF for interspecies differences (allometric scaling):

1

Justification:

An assessment factor for allometric scaling is not needed since local effects are independent of the basal metabolic rate; allometric scaling should not be applied (ECHA, Guidance, Chapter R.8).

AF for other interspecies differences:

1

Justification:

The assessment factor for remaining uncertainties can be 1. For vehicle effects: an assessment factor of 1 is applied as the matrices of the products compiled from the substance are not intended to enhance penetration. For type of skin (skin thickness and skin integrity) it can be seen that the human skin (exposed hands) to be similarly or less sensitive compared to the skin of the mouse ear. The LLNA is selected as a model because the mouse ear is considered very thin with high blood flow and as such reflect a similar thickness and integrity compared to human skin in general

AF for intraspecies differences:

10

Justification:

Intraspecies differences in human result from a multitude of biological factors such as genetic polymorphism affecting e.g. toxicokinetics/metabolism, age, gender, health status and nutritional status. For the general population, as standard procedure for threshold effects a default assessment factor of 10 is to be used, based on the fact that the all sub-populations are covered in this population: the very young, the very old, and the very ill (ECHA Guidance, Chapter R.8).

AF for the quality of the whole database:

1

Justification:

The evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended (ECHA Guidance, Chapter R.8).

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, is recommended (ECHA Guidance, Chapter R.8).

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:

0.08 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Overall assessment factor (AF):

200

Dose descriptor starting point:

NOAEL

Value:

16 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A NOAEL of 10 mg/kg bw/day (males / females) was established in this study based on, haemolysis and haemosiderosis in spleen and kidney. Applying a correction for molecular weight, this results in a NOAEL of 10 x (227/143) = 16 mg/kg bw/day.

AF for dose response relationship:

1

Justification:

The starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor of 1 is used (ECHA Guidance, Chapter R.8).

AF for differences in duration of exposure:

2

Justification:

A factor of 2 is dictated from a 90-day study to chronic toxicity (ECHA Guidance, Chapter R.8).

AF for interspecies differences (allometric scaling):

4

Justification:

Differences in metabolic rate (allometric scaling) should be accounted for by extrapolation of doses according to an overall assumption that equitoxic doses (when expressed in mg/kg bw/day) scale with body weight to the power of 0.75. This results in different default allometric scaling factors for the different animal species when compared with humans. For rats, the default assessment factor is 4 (ECHA Guidance, Chapter R.8).

AF for other interspecies differences:

2.5

Justification:

Interspecies differences result from variation in the sensitivity of species due to differences in toxicokinetics and toxicodynamics. Some of the toxicokinetic differences can be explained by differences in body size (and related differences in basal metabolic rate). As no substance-specific data are available, the standard procedure for threshold effects is followed. As a default, an additional factor of 2.5 for interspecies differences (other than allometric scaling), i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part) is applied (ECHA Guidance, Chapter R.8).

AF for intraspecies differences:

10

Justification:

Intraspecies differences in human result from a multitude of biological factors such as genetic polymorphism affecting e.g. toxicokinetics/metabolism, age, gender, health status and nutritional status . For the general population, as standard procedure for threshold effects a default assessment factor of 10 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill (ECHA Guidance, Chapter R.8).

AF for the quality of the whole database:

1

Justification:

The evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended (ECHA Guidance, Chapter R.8).

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, is recommended (ECHA Guidance, Chapter R.8).

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)