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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
44 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
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:
12.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
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

A DNEL for acute dermal toxicity is not established because no acute toxicity hazard (leading to classification and labelling) has been identified. For the inhalation route no studies are available.

A reliable dose descriptor for local irritation, acute or long term exposure, could not be derived from the available acute dermal toxicity study. Long term studies are available only for the oral route of exposure.

In skin irritation studies conducted according to EU Method B.4 and/or OECD Guideline 404, AAPBs are only very slightly irritating to rabbit skin with mean values lower than cut-off values triggering classification. A DNEL for acute toxicity local effects of skin is not established because no hazard for skin irritation (leading to classification and labelling) has been identified. The observed slight to well-defined fully reversible erythema (no oedema) under extreme exposure conditions (24 h occlusive treatment), is considered to be not relevant to human health hazard assessment, because the occurrence of such extreme conditions is very unlikely at work place and professional use.

In eye irritation studies conducted according to EU Method B.5 and/or OECD Guideline 405, AAPBs with concentrations of ≥ 25 % a. i. caused severe irreversible eye effects. Thus AAPBs have to be classified as eye irritant Category 1. Reliable data for the implementation of specific concentration limits (SCL), according to article 10 of GHS Regulation EC No 1272/2008, are available. For eye irritation Category 1 a specific concentration limit (SCL) of > 10 % and for eye irritation Category 2 a SCL of > 4 % ≤ 10 % is established for mixtures containing AAPB. This implies, mixtures containing ≤ 4 % AAPB need not to be classified for eye irritation. For handling therespective risk management measures (RMMs) for each concentration range are implemented.

From skin and eye irritation studies it cannot be assumed whether a potential risk for respiratory tract irritation may exist.

For long-term exposure – systemic effects the following DNELs were derived:

Dermal: 12.5 mg/kg bw/day

The long-term dermal DNEL has to be established by route-to-route extrapolation from the oral repeated dose toxicity study. ADME studies on C12 AAPB in rats show that in the worst case 10 % of an oral dose is absorbed, whereas in the worst case (under occlusive conditions) approximately 6 % and 2 % absorption occurred after dermal application in females and males, respectively. Absorption after non occluded rinsed dermal application was < 0.2 % in males and females.

In an in vitro study on dermal resorption performed on human skin, the resorption rate was zero.

For DNEL calculation, as default values an each 10 % absorption is assumed after oral and dermal administration of the test substance. Particularly for the dermal route, which is due to the use profile of the substance the most important exposure route to humans, this is a very conservative worst case assumption, since a reliable in vitro study on human skin showed a dermal resorption rate of zero.

The corrected dermal NOAEL for worker systemic effects is: 300 x 1 = 300 mg/kg/day.

Justification for applied assessment factors: 

The starting point is an oral dose descriptor from a rat study. It is therefore necessary to include an allometric scaling factor of 4 to take account of differences in basal metabolic rates between rats and humans (cf ECETOC Guidance on Assessment Factors to Derive DNELs (Draft, CEFIC, March, 2010)).There are no data for AAPB to quantify other differences between animals and humans that could affect extrapolation. There are no data to quantify variability in susceptibility to the effects of long-term exposure to AAPB in the human population. The default factor of 3 for workers will therefore be used to take account of intraspecies variability (cf ECETOC Guidance on Assessment Factors to Derive DNELs (Draft, CEFIC, March, 2010)). For differences in duration of exposure a factor of 2 was applied to correct for sub-chronic to chronic, resulting in an overall assessment factor of 24.

Inhalation: 44 mg/m³

The NOAEL for systemic toxicity identified from an oral 90-day- study on C8-18 AAPB in the rat was 300 mg/kg bw/day. Inhalatory absorption data are missing. Absorption after oral or dermal exposure in a reliable experimental study on rats was 10 % in maximum. The amounts of inhalative absorption deduced from the physico-chemical properties and from the results of oral and dermal absorption studies are expected to be low.AAPBs are visually unlimited soluble in water, CMC (critical micelle concentration) formation ranged from 250 – 900 mg/L, a weighted mean Log Kow of 4.2 was calculated and the vapour pressure is expected to be very low.Further on, AAPBs are amphoterics and the inhalative absorption of ionic substances is generally low. Taken together, based on physico-chemical properties of the respective AAPBs, a low bioavailability could be anticipated. As a worst case assumption, twice the measured values for oral and dermal absorption are assumed for absorption after inhalative exposure in absence of any experimental data on inhalative exposure.

For the derivation of a NOAEC for the worker the following corrections have to be applied to the NOAEL (rat). The oral NOAEL (rat) is adjusted to Inhalation (factor 0.38 m³/kg bw/8h (default respiratory volume in rat, Table R.8.2 of ECHA R.8 guidance on DNELs) to give the corresponding rat inhalation 8h-NOAEC (no-observed adverse effect concentration). To adjust the NOAEL/NOEC for bioavailability this value is multiplied with 0.5 (x10/20). To obtain the starting point for workers, a factor of 0.67 is applied to the NOAEC to account for the differences in inhalation rates between animals at rest and humans involved in light activity.

The corrected inhalatory NOAECworker (8h) is therefore: = 264 mg/m³ (8h-TWA)

Justification for applied assessment factors: 

It is not necessary to apply an allometric scaling factor because the starting point has been corrected for differences in respiratory volume and this takes account of differences in metabolic rates (cf ECETOC Guidance on Assessment Factors to Derive DNELs (Draft, CEFIC, March, 2010)). There are no data to quantify variability in susceptibility to the effects of long-term exposure to AAPB in the human population. The default factor of 3 for workers will therefore be used to take account of intraspecies variability (cf ECETOC Guidance on Assessment Factors to Derive DNELs (Draft, CEFIC, March, 2010)). For differences in duration of exposure a factor of 2 was applied to correct for sub-chronic to chronic, resulting in an overall assessment factor of 6.

 


General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
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:
7.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
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:
7.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

A DNEL for acute dermal toxicity is not established because no acute toxicity hazard (leading to classification and labelling) has been identified. For the inhalation route no studies are available.

A reliable dose descriptor for local irritation, acute or long term exposure, could not be derived from the available acute dermal toxicity study. Long term studies are available only for the oral route of exposure.

In skin irritation studies conducted according to EU Method B.4 and/or OECD Guideline 404, AAPBs are only very slightly irritating to rabbit skin with mean values lower than cut-off values triggering classification. A DNEL for acute toxicity local effects of skin is not established because no hazard for skin irritation (leading to classification and labelling) has been identified. The observed slight to well-defined fully reversible erythema (no oedema) under extreme exposure conditions (24 h occlusive treatment), is considered to be not relevant to human health hazard assessment, because the occurrence of such extreme conditions is very unlikely at consumer use.

In eye irritation studies conducted according to EU Method B.5 and/or OECD Guideline 405, AAPBs with concentrations of ≥ 25 % a. i. caused severe irreversible eye effects. Thus AAPBs have to be classified as eye irritant Category 1. Reliable data for the implementation of specific concentration limits (SCL), according to article 10 of GHS Regulation EC No 1272/2008, are available. For eye irritation Category 1 a specific concentration limit (SCL) of > 10 % and for eye irritation Category 2 a SCL of > 4 % ≤ 10 % is established for mixtures containing AAPB. This implies, mixtures containing ≤ 4 % AAPB need not to be classified for eye irritation. For handling therespective risk management measures (RMMs) for each concentration range are implemented.

Long term studies are available only for the oral route of exposure. A DNEL long term inhalation has not been derived since this kind of exposure is not relevant for consumer applications. AAPBs do have very low vapour pressure, so the potential for the generation of inhalable forms is low, also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur.

For long-term exposure – systemic effects the following DNELs were derived:

Dermal: 7.5 mg/kg bw/day

The long-term dermal DNEL has to be established by route-to-route extrapolation from the oral repeated dose toxicity study. ADME studies on C12 AAPB in rats show that in the worst case 10 % of an oral dose is absorbed, whereas in the worst case (under occlusive conditions) approximately 6 % and 2 % absorption occurred after dermal application in females and males, respectively. Absorption after non occluded rinsed dermal application was < 0.2 % in males and females.

In an in vitro study on dermal resorption performed on human skin, the resorption rate was zero.

For DNEL calculation, as default values an each 10 % absorption is assumed after oral and dermal administration of the test substance. Particularly for the dermal route, which is due to the use profile of the substance the most important exposure route to humans, this is a very conservative worst case assumption, since a reliable in vitro study on human skin showed a dermal resorption rate of zero.

The corrected dermal NOAEL for the general population systemic effects is: 300 x 1 = 300 mg/kg/day

Justification for applied assessment factors: 

The starting point is an oral dose descriptor from a rat study. It is therefore necessary to include an allometric scaling factor of 4 to take account of differences in basal metabolic rates between rats and humans (cf ECETOC Guidance on Assessment Factors to Derive DNELs (Draft, CEFIC, March, 2010)). There are no data for AAPB to quantify other differences between animals and humans that could affect extrapolation. There are no data to quantify variability in susceptibility to the effects of long-term exposure to AAPB in the human population. The default factor of 5 for general population will therefore be used to take account of intraspecies variability (cf ECETOC Guidance on Assessment Factors to Derive DNELs (Draft, CEFIC, March, 2010)). For differences in duration of exposure a factor of 2 was applied to correct for sub-chronic to chronic, resulting in an overall assessment factor of 40.

Oral: 7.5 mg/kg bw/day

The long term DNEL for general population was derived from the oral 90-day oral study with rats (NOEL 300 mg/kg bw/day).

The following assessment factors were applied:

4 for interspecies variability, 5 for intraspecies variability general population and 2 for time extrapolation (cf ECETOC Guidance on Assessment Factors to Derive DNELs (Draft, CEFIC, March, 2010)). This results in an overall assessment factor of 40.