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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:
11.76 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
882 mg/m³
Explanation for the modification of the dose descriptor starting point:
The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation route to route extrapolation.
AF for differences in duration of exposure:
6
Justification:
subacute to chronic extrapolation
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
Justification:
remaining difference
AF for intraspecies differences:
5
Justification:
Worker population
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
83.33 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Value:
25 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Based on the exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %. Therefore, a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Workers- Hazard via inhalation route: Systemic effects, Long-term exposure:

Since there is no dose descriptor for inhalation exposure, dose descriptors were converted into a correct starting point by route-to-route extrapolation based on the ECHA guidance document R.8: Characterisation of dose [concentration]-response for human health", Dec 2010. The conversion of an oral NOAEL into an inhalatory NAEC is performed using the following equations: for workers the resulting concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity

Corrected inhalatory NOAEC = oral NOAEL x 1/sRVratx ABSoral-rat/ ABSinh-humanx sRVhuman/wRV

= 1000 mg/kg bw /dx 1/0.38m³/kg bw x 0.5 x 6.7 m³/10 m³

= 881.57 mg/m³

SRV: standard respiratory volume, ABS: absorption, wRV: worker respiratory volume. For the route-to-route extrapolation (oral to inhalation) the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rats (0.38 m³/kg for 8 hours exposure of workers). The resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity (6.7 m³/worker for basal activity, 10 m³/worker in 8 hours for light activity). Since NOAEL value was derived from reproduction/developmental oral toxicity study (OECD 421) , a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation route. According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation.

The corrected NOAEC was divided by an assessment factor of 75, derived from 2.5, interspecies, remaining differences), 5 (intraspecies, worker) and 6 (exposure duration, subacute to chronic). The long-term DNEL, inhalation for systemic effects of 11.76 mg/m3 is derived.

Workers- Hazard via dermal route: Systemic effects, Long-term exposure:

The conversion of an oral NOAEL into a dermal NAEC is performed using the following equations:

Corrected dermal NAEL = oral NOAEL x ABSoral-rat/ABSdermal                                      

                                       = oral NOAEL x 50/2

ABS: absorption

Based on the exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %.

The worker dermal starting point was NOAEL value of 1000 mg/kg bw/day obtained from Reproduction / Developmental Toxicity Screening Test according to OECD Guideline 421. In the 28 day repeated-dose study performed with RA substance, NOAEL value was also found similar. The corrected NOAEL value of 25000 mg/kg bw/day as divided by an assessment factor of 300. The overall assessment factor of 300 was derived combining a factor of 10 (interspecies), 5 (intraspecies, worker) and 6 (exposure duration subacute to chronic), resulting in a dermal DNEL for workers of 83.3 mg/kg bw/d.

Acute effects:

Based on the acute toxicity data, DNELs do not need to be derived for acute effects for the worker population since the substance has a low potential for acute toxicity. The substance is classified as skin sensitizer, however, since only a Buehler test results are available, no DNEL could be derived. Because of sensitising effect, the hazard assessment conclusion for local acute effect of dermal route was indicated as 'medium hazard'.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
Value:
434.78 mg/m³
Explanation for the modification of the dose descriptor starting point:
The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation extrapolation.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
subacute to chronic extrapolation
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
Consumer population
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
41.67 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
25 000
Explanation for the modification of the dose descriptor starting point:
Based on the exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %. Therefore, a factor of 25 was taken into consideration as worst case for the oral to dermal route to route extrapolation.
AF for dose response relationship:
6
Justification:
subacute to chronic extrapolation
AF for differences in duration of exposure:
4
Justification:
rat to human extrapolation
AF for interspecies differences (allometric scaling):
2.5
AF for other interspecies differences:
10
Justification:
general population
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
1.67 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation applied.
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human extrapolation
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General population- Hazard via inhalation route: Systemic effects, Long-term exposure:

Since there is no dose descriptor for inhalation exposure, dose descriptors were converted into a correct starting point by route-to-route extrapolation based on the ECHA guidance document R.8: Characterisation of dose [concentration]-response for human health", Dec 2010.

Corrected inhalatory NOAEC = oral NOAEL x 1/sRVratx ABSoral-rat/ ABSinh-humanx sRVhuman/wRV

= 1000 mg/kg bw x1/1.15m³/kg bw x 0.5

= 434.78mg/m³

For the route-to-route extrapolation (oral to inhalation) the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rats (1.15 m³/kg for general population).

Since NOAEL value was derived from reproduction/developmental oral toxicity study (OECD 421), a route-to-route extrapolation is needed to derive the DNELs for dermal and inhalation route.According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation. The corrected NOAEC was divided by an assessment factor of 150, derived from 2.5, interspecies, remaining differences), 10 (intraspecies, general population) and 6(exposure duration, subacute to chronic). The long-term DNEL, inhalation for systemic effects of 2.9 mg/m3 is derived.

General Population- Hazard via dermal route: Systemic effects, Long-term exposure:

The conversion of an oral NOAEL into a dermal NAEC is performed using the following equations:

Corrected dermal NAEL = oral NOAEL x ABSoral-rat/ABSdermal                                      

                                       = oral NOAEL x 50/2

ABS: absorption

Based on the exposure model from AG Textilien des Bundesinstituts für Risikobewertung (BfR), the dermal penetration rate for dyes through the skin was found to be less than 2 %.

The general population dermal starting point was NOAEL value of 1000 mg/kg bw/day obtained from Reproduction / Developmental Toxicity Screening Test according to OECD Guideline 421.

In the 28 day repeated-dose study performed with RA substance, NOAEL value was also found similar. The corrected NOAEL value of 25000 mg/kg bw/day as divided by an assessment factor of 600. The overall assessment factor of 600 was derived combining a factor of 10 (interspecies), 5 (intraspecies, general population) and 6 (exposure duration subacute to chronic), resulting in a dermal DNEL for workers of 41.67 mg/kg bw/d.

General population- Hazard via oral route: Systemic effects, Long-term exposure:

The NOAEL value from Reproduction / Developmental Toxicity Screening Test according to OECD Guideline 421 will be used for calculation. In the 28-day repeated-dose study performed with RA substance, NOAEL value was also found similar. The NOAEL value of 1000 mg/kg bw/day was divided by an assessment factor of 600 derived combining a factor of 10 (interspecies), 10 (intraspecies, consumer) and 6 (exposure duration subchronic to chronic).

Acute effects:

Based on the acute toxicity data, DNELs do not need to be derived for acute effects for the general population since the substance has a low potential for acute toxicity.The substance is classified as skin sensitizer, however, since only a Buehler test results are available, no DNEL could be derived. Because of sensitising effect, the hazard assessment conclusion for local acute effect of dermal route was indicated as 'medium hazard'.