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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
58.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Additional information - workers

No DNELs have been derived for the short-term dermal and inhalation exposure of 2-(2-hexyl-decyloxy)-benzamide (SP-334/TS-2863) for workers, as it is assumed that the assessment of hazard is sufficiently covered by deriving the respective DNELs for long-term exposure.

No quantitative dose-response data are available for local short-term effects on skin and respiratory tract of 2-(2-hexyl-decolyl)-benzamide. Therefore, an absolute value for the local effects has been determined. The test substance was not skin or eye irritating (Pels Rijcken 1999; Pels Rijcken, 1998). 

The long-term worker DNEL for dermal systemic effects is based on the 28 -day repeated dose toxicity study performed according to OECD 407 in rats (Pels Rijcken, 1998). In this study there was no substance-related mortality, and no effects with toxicological relevance were observed on body weights, organ weights, haematologic and clinical chemistry parameters, or gross and histopathologic examinations. As no effects were observed up to and including the highest dose level, the NOAEL is ≥ 1000 mg/kg bw/d. This study was chosen as the starting point for deriving the DNEL as there is no dermal repeated dose study. To convert the oral NOAEL [mg/kg bw/day] into a dermal NOAEL [mg/kg bw/day], the differences in absorption between routes as well as differences in dermal absorption between rats and humans have to be accounted for (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health, European Chemicals Agency, December 2010). For 2-(2-hexyl-decyloxy)-benzamide, the dermal bioavailability is expected to be in the same order of magnitude as oral absorption (see section 7.1 Toxicokinetics). The NOAEL for the oral and dermal exposure route is therefore identical. As the toxicokinetic data indicates a very low oral and dermal bioavailability, the assessment factor (AF) 0.5 has been used.

 

The long-term worker DNEL for inhalation systemic effects is again based on the 28 -day repeated dose toxicity study performed according to OECD 407 in rats (Pels Rijcken, 1998e). This study was chosen as the starting point for deriving the DNEL as there is no inhalation repeated dose study. According to the 'Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health' (European Chemicals Agency, December 2010), the oral NOAEL should be converted into an inhalatory NAEC: the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m3/kg for 8 h exposure). Additionally, it should be taken into account that during 8 hours light activity at work the respiratory rate becomes higher (10 m3/person) than standard (6.7 m3/person). Considering these differences, the correct starting point is a NAEC of 1763.2 mg/m3. The absorption via the inhalative route is considered to be higher than via the oral route and there is no inhalation data to justify a refinement. Therefore, an AF of 1 for differences in absorption between the inhalation and oral route is applied by default. An AF of 6 for exposure duration is applied to take into account the difference between experimental exposure duration and the exposure duration for the population.

In general, AFs recommended by ECHA (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose[concentration]-response for human health. European Chemicals Agency, December 2010) were used when applicable to derive the DNELs. One AF for which there is additional information was refined. The AF for remaining interspecies differences has been set at 1, as the toxicokinetic data indicates that 2-(2-hexyl-decyloxy)-benzamide will not be metabolised. As it is practically water-insoluble, the substance also has very low bioavailability (see section 7.1 Toxicokinetics).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The general population is not exposed to 2-(2-hexyl-decyloxy)-benzamide (SP-334/TS-2863), based on its identified uses. However, the long-term consumer DNEL for oral, dermal and inhalation systemic effects have been derived.

No DNELs have been derived for the short-term dermal and inhalation exposure of 2-(2-hexyl-decolyl)-benzamide for the general population, as it is assumed that the assessment of hazard is sufficiently covered by deriving the respective DNELs for long-term exposure.

No quantitative dose-response data are available for local short-term effects on skin and respiratory tract of 2-(2-hexyl-decolyl)-benzamide. Therefore, an absolute value for the local effects has been determined. The test substance was not skin or eye irritating (Pels Rijcken 1999; Pels Rijcken, 1998). 

 

The long-term DNEL for the general population, dermal systemic effects is based on the 28 -day repeated dose toxicity study performed according to OECD 407 in rats (Pels Rijcken, 1998). In this study there was no substance-related mortality, and no effects with toxicological relevance were observed on body weights, organ weights, haematologic and clinical chemistry parameters, or gross and histopathologic examinations. As no effects were observed up to and including the highest dose level, the NOAEL is ≥ 1000 mg/kg bw/d. This study was chosen as the starting point for deriving the DNEL as there is no dermal repeated dose study. To convert the oral NOAEL [mg/kg bw/day] into a dermal NOAEL [mg/kg bw/day], the differences in absorption between routes as well as differences in dermal absorption between rats and humans have to be accounted for (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. European Chemicals Agency, December 2010). For 2-(2-hexyl-decyloxy)-benzamide, the dermal bioavailability is expected to be in the same order of magnitude as oral absorption (see section 7.1 Toxicokinetics). The NOAEL for the oral and dermal exposure route is therefore identical. As the toxicokinetic data indicates a very low oral and dermal bioavailability, the assessment factor (AF) 0.5 has been used.

 

The long-term DNEL for the general population, inhalation systemic effects is also based on the 28 -day repeated dose toxicity study performed according to OECD 407 in rats (Pels Rijcken, 1998). This study was chosen as the starting point for deriving the DNEL as there is no inhalation repeated dose study. According to the Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health' (European Chemicals Agency, December 2010), the oral NOAEL should be converted into an inhalatory NAEC: the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m ³/kg for 24 h exposure). Therefore, the corrected starting point is a NAEC of 869.6 mg/ m³. The absorption via the inhalative route is considered to be higher than via the oral route and there is no inhalation data to justify a refinement. Therefore, an AF of 1 for differences in absorption between the inhalation and oral route is applied by default.

 

The long-term DNEL for the general population, oral systemic effects is also based on the 28 -day repeated dose toxicity study (Pels Rijcken, 1998) performed according to OECD 407 in rats. In this study, there was no substance-related mortality, and no treatment-related effects were observed on body weights, organ weights, haematologic and clinical chemistry parameters, or gross and histopathologic examinations. As no effects were observed up to and including the highest dose level, the NOAEL is ≥ 1000 mg/kg bw/d. The study was performed via the oral route and the value can be used directly to derive the oral DNEL.

An AF of 6 for exposure duration is applied to take into account the difference between experimental exposure duration and the exposure duration for the general population.

In general, AFs recommended by ECHA (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose[concentration]-response for human health. European Chemicals Agency, December 2010) were used when applicable to derive the DNELs. One AF for which there is additional information was refined. The AF for remaining interspecies differences has been set at 1, as the toxicokinetic data indicates that 2-(2-hexyl-decyloxy)-benzamide will not be metabolised. As it is practically water-insoluble, the substance also has very low bioavailability (see section 7.1 Toxicokinetics).

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