Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.6 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:

85 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

188.8 mg/m³

Explanation for the modification of the dose descriptor starting point:

The substance fulfils the REACH information requirements in accordance with ECHA guidance R7.5-7.7 (2016) 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. The starting point is the NOAEL obtained from a 9-months oral study in rats on read-across substance LAS natrium (CAS 69669-449); 85 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/day). A factor for route-to-route extrapolation is included based on experimentally derived oral absorption (90%) and the default inhalation absorption values (R.7.12. June 2017). 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): 85 * (1/0.38) * (90/100)* (6.7/10) * (7/5) = 188.8 mg/m³.

AF for dose response relationship:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose,…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case 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, as a standard procedure, is 1.

AF for differences in duration of exposure:

2

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. For a sub-chronic toxicity study, an assessment factor of 2 is to be applied, as a standard procedure.

AF for interspecies differences (allometric scaling):

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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. In this case, route-to-route extrapolation is performed form 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:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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.

AF for intraspecies differences:

5

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. 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:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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.

AF for remaining uncertainties:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, there are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.

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:

119 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:

85 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

11 900 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The substance fulfils the REACH information requirements in accordance with ECHA guidance R7.5-7.7 (2016) for assessing long-term systemic toxicity. Since no repeated dose dermal study is available, route-to-route extrapolation from the oral exposure route is performed. The starting point is the NOAEL obtained from a 9-months oral study in rats on read-across substance LAS natrium (CAS 69669-449); 85 mg/kg bw/day.

A dermal absorption study of a C12 LAS homologue in isolated human epidermis (Howes, 1975) indicated that < 0.065% of the applied dose penetrated the skin in 48 hours. An oral absorption value of 90% was experimentally derived. A route-to-route factor of 100, instead of 90/0.065=1384.6, was conservatively assumed. A correction for 5 day exposure is performed (7 days exposure per week in the study versus 5 days per week for workers): 85 * 100 * (7/5) = 11 900 mg/kg bw/day.

AF for dose response relationship:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose,…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case 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, as a standard procedure, is 1.

AF for differences in duration of exposure:

2

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. For a sub-chronic toxicity study, an assessment factor of 2 is to be applied, as a standard procedure.

AF for interspecies differences (allometric scaling):

4

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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, as a standard procedure, is 4.

AF for other interspecies differences:

2.5

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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.

AF for intraspecies differences:

5

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. 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:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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.

AF for remaining uncertainties:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, there are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.

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:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

LAB Sulfonic Acids are used as intermediates in the production of LAS. In many, but not all, cases the intermediates are site limited, i.e., they remain on the production facility for use in the LAS production process. In some cases the intermediates are sold to outside LAS manufacturers. Transport to these off-site facilities is conducted following strict health and safety procedures and DOT requirements.

All processing of LAB and LAB sulfonic acids takes place in closed systems that significantly minimize worker exposure. Workers also wear standard personal protective equipment including safety goggles, face shields, safety shoes, impervious nitrile gloves, long sleeved clothing, and rubber boots. Workers may also employ cartridge-type respirators equipped with organic vapor cartridges and acid-resistant suits, for example, during steaming and washing. The closed production process and use of personal protective equipment effectively eliminates exposure to production workers. Un-ionized LAB Sulfonic Acid is not present after neutralization during manufacture of LAS detergent products. Consumer exposure to trace levels of LAB Sulfonic Acids from detergent use is possible.

Extensive engineering controls are in place to minimize releases to the environment. These controls include SO₂/SO₃monitoring devices, spill containment dikes for rail unloading, leak inspections, high level tank alarms, and auto shut off valves. Emissions controls include line cyclones, electrostatic precipitation and passing through caustic scrubbers and scrubbing demisters. Some process wastewater is deep well injected. These practices and controls effectively reduce LAB Sulfonic Acid releases to the environment to levels far below the allowable amounts, as shown by process stack monitoring.

Because LAB Sulfonic Acids are intermediates in the production of LAS, the derivation of DNELs is performed using the data for LAS where appropriate and the data for LAB Sulfonic Acids where available. LAS is used in light-duty liquid dishwashing compounds, heavy-duty liquid and powder laundry detergents, all-purpose cleaners and industrial cleaners. Industrial cleaning professionals and consumers may be exposed to small amounts of LAB Sulfonic Acid contained in these products. Given these uses, and as recommended in Chapter R.8 of the REACH guidance documents, long-term DNELs were derived for workers potentially exposed through the dermal  and inhalation routes of exposure and for consumers through the oral, dermal and inhalation routes of exposure. As noted in R.8, “for most substances and exposure scenarios the DNEL_long-term will be sufficient for controlling risks.”

Overall, LAB Sulfonic Acids show relatively low toxicity, with an acute oral LD₅₀of 1470 mg/kg and no effects observed in acute dermal testing. Undiluted LAB Sulfonic Acid is irritating to the skin and eyes and is classified under the CLP as category 1B skin corrosive, eye severely irritating. LAB Sulfonic Acid is not a skin sensitizer and is not mutagenic. Effects in long-term repeated dose studies conducted on LAS and lasting up to 9 months (subchronic studies) are related to enzymatic, body and organ weight reductions but not mortality. No significant reproductive or developmental effects were observed in long-term testing with LAS. The most appropriate NOAEL from the long-term oral repeated dose toxicity test (85 mg/kg based on decreases in enzymatic activity in the 145 mg/kg bw/d dose in the Yoneyama et al. 1976 study) is the value used as a starting point for deriving the DNEL_{long-term, oral ,}the DNEL_{long-term, dermal}, and the DNEL_{long-term, inhalation}, as appropriate, for worker and consumer exposures. The NOAEL of 85 mg/kg is most appropriate because it is the highest NOAEL below the lowest LOAEL in long-term studies.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.3 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:

85 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

66.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

The substance fulfils the REACH information requirements in accordance with ECHA guidance R7.5-7.7 (2016) 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. The starting point is the NOAEL obtained from a 9-months oral study in rats on read-across substance LAS natrium (CAS 69669-449); 85 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/day). A factor for route-to-route extrapolation is included based on experimentally derived oral absorption (90%) and the default inhalation absorption values (R.7.12. June 2017): 85 * (1/1.15) * (90/100) = 66.5 mg/m³.

AF for dose response relationship:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case 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, as a standard procedure, is 1.

AF for differences in duration of exposure:

2

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. For a sub-chronic toxicity study, an assessment factor of 2 is to be applied, as a standard procedure.

AF for interspecies differences (allometric scaling):

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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. In this case, route-to-route extrapolation is performed form 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:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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.

AF for intraspecies differences:

10

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-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. For consumers, 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.

AF for the quality of the whole database:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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.

AF for remaining uncertainties:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, there are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.

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:

42.5 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

Dose descriptor starting point:

NOAEL

Value:

85 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

8 500 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The substance fulfils the REACH information requirements in accordance with ECHA guidance R7.5-7.7 (2016) for assessing long-term systemic toxicity. Since no repeated dose dermal study is available, route-to-route extrapolation from the oral exposure route is performed. The starting point is the NOAEL obtained from a 9-months oral study in rats on read-across substance LAS natrium (CAS 69669-449); 85 mg/kg bw/day.Based on data from a dermal absorption study of a C12 LAS homologue in isolated human epidermis (Howes, 1975) that indicated < 0.065% of the applied dose penetrated the skin in 48 hours. An oral absorption value of 90% was experimentally derived. A route-to-route factor of 100, instead of 90/0.065=1384.6, was conservatively assumed: 85 * 100 = 8 500 mg/kg bw/day.

AF for dose response relationship:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case 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, as a standard procedure, is 1.

AF for differences in duration of exposure:

2

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. For a sub-chronic toxicity study, an assessment factor of 2 is to be applied, as a standard procedure.

AF for interspecies differences (allometric scaling):

4

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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, as a standard procedure, is 4.

AF for other interspecies differences:

2.5

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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.

AF for intraspecies differences:

10

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-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. For consumers, 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.

AF for the quality of the whole database:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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.

AF for remaining uncertainties:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, there are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.

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:

medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.425 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:

85 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The substance fulfils the REACH information requirements in accordance with ECHA guidance R7.5-7.7 (2016) for assessing long-term systemic toxicity. The starting point is the NOAEL obtained from a 9-months oral study in rats on read-across substance LAS natrium (CAS 69669-449); 85 mg/kg bw/day.

AF for dose response relationship:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case 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, as a standard procedure, is 1.

AF for differences in duration of exposure:

2

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. For a sub-chronic toxicity study, an assessment factor of 2 is to be applied, as a standard procedure.

AF for interspecies differences (allometric scaling):

4

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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, as a standard procedure, is 4.

AF for other interspecies differences:

2.5

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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.

AF for intraspecies differences:

10

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-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. For consumers, 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.

AF for the quality of the whole database:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, 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.

AF for remaining uncertainties:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, there are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)