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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:
2.351 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
DNEL value:
176.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalation study available
AF for dose response relationship:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for differences in duration of exposure:
6
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for other interspecies differences:
2.5
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for intraspecies differences:
5
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for the quality of the whole database:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for remaining uncertainties:
2.5
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
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:
0.333 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):
300
Modified dose descriptor starting point:
NOAEL
DNEL value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No dermal long-term study available
AF for dose response relationship:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for differences in duration of exposure:
6
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for interspecies differences (allometric scaling):
4
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for other interspecies differences:
2.5
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for intraspecies differences:
5
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for the quality of the whole database:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Acute toxicity

ECHA Guidance R.8 (Chapter R.8.1.2.5) indicates that DNELs for acute toxicity are not required if no acute toxicity hazard leading to classification has been identified. The substance 2,5-Furandione, dihydro-, mono-C15-20-alkenyl derivs. is not found to be acutely toxic following oral or dermal exposure (LD50 >2000 mg/kg bw) while a low vapour pressure precludes inhalation exposure indicating a low of concern for this route of exposure. No DNELs for acute toxicity are therefore necessary.

Sensitisation

The substance 2,5-Furandione, dihydro-, mono-C15-20-alkenyl derivs. is classified as sensitizing to skin due to the positive results in a Guinea pig maximization test (GPMT).

ECHA Guidance R.8, Appendix R.8-10, (ECHA, 2010) states that skin sensitisation is generally regarded as a threshold effect and thus it may be very difficult to derive a threshold and to set a DNEL. The general approach for sensitizers therefore involves a qualitative approach where a DNEL is used to judge any remaining/residual risks after the implementation of appropriate risk management measures (RMM) and occupational controls (OC).

The extent of the RMM and OC required is dependent on the intrinsic sensitising potency of the substance.

For results obtained using the GPMT, intrinsic sensitising potency is based on the percentage of positive animals in relation to the induction concentration tested.

Based on the 5% intradermal concentration employed during induction phase and the 50% incidence of sensitisation 2,5-Furandione, dihydro-, mono-C15-20-alkenyl derivs. is therefore regarded as having moderate potency to cause skin sensitisation.

 

Repeated dose toxicity

Inhalation

The lowest effect level for oral repeated dose toxicity was found to be the NOAEL of 100 mg/kg bw/d and thus used for the purposes of DNEL derivation for the inhalation route.

Relevant dose descriptors have been developed for the different endpoints and routes of exposure (see Guidance Document, Chapter R.8, Appendix R.8-2). The values are provided below. For potential inhalation exposures, route-to-route extrapolations from the oral NOAEL value are performed:

To convert oral NOAEL into inhalator in NOAEC, a rat default respiratory volume is used corresponding to the daily duration of human exposure (sRVrat: 0.38 m3/kg bw/8 h).

For workers a correction is added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3for an 8-h exposure period) and under conditions of light activity (wRV: 10 m3for an 8-h exposure period).

The corrected inhalation NOAEC for workers is:

inhalation NOAEC = oral NOAEL * (1/ sRV rat 8h) * (ABS oral / ABS inh) * (sRV human / wRV)

inhalation NOAEC= 100 * (1/0.38) * (100/100) * (6.7 / 10)

inhalation NOAEC = 176.3 mg/m³

In general ECHA Guidance R.8 suggests a factor 2 for route-to-route extrapolation from oral to inhalation to account for general higher uptake by the lung. However, based on the low vapor pressure, the logP value and the low water solubility this value is not justified. Thus, inhalation is assumed to be low and equal to oral absorption for the purposes of the DNEL calculation.

Additional assessment factors (AF) are applied to derive the DNEL. The AFs were based on the procedures described ECHA Guidance R.8

Long-term DNEL Assessment Factors (Inhalation)

Assessment Factor

Worker

Differences in metabolic rate per b. w. (allometric scaling)

-

Interspecies remaining differences (toxicodynamic and toxicokinetic)

2.5

Intraspecies differences

5

Duration extrapolation

(sub-acute/sub-chronic/chronic)

6 (sub-acute)

Issues related to dose-response

1

Quality of whole database

1

Overall AF

75

 

Dermal

The lowest effect level for oral repeated dose toxicity was found to be the NOAEL of 100 mg/kg bw/d and thus used for the purposes of DNEL derivation for the inhalation route.

Based on the low vapor pressure, the logP value and the low water solubility the dermal absorption can be regarded as low.

Additional assessment factors (AF) are applied to derive the DNEL. The AFs were based on the procedures described ECHA Guidance R.8

Long-term DNEL Assessment Factors (Dermal)

Assessment Factor

Worker

Differences in metabolic rate per b. w. (allometric scaling)

4

Interspecies remaining differences (toxicodynamic and toxicokinetic)

2.5

Intraspecies differences

5

Duration extrapolation

(sub-acute/sub-chronic/chronic)

6 (subchronic)

Issues related to dose-response

1

Quality of whole database

1

Overall AF

300

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 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):
150
Modified dose descriptor starting point:
NOAEC
DNEL value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalation study available
AF for dose response relationship:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for differences in duration of exposure:
6
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for other interspecies differences:
2.5
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for intraspecies differences:
10
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for the quality of the whole database:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for remaining uncertainties:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
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:
0.167 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
DNEL value:
100
Explanation for the modification of the dose descriptor starting point:
No dermal long-term study available
AF for dose response relationship:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for differences in duration of exposure:
6
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for interspecies differences (allometric scaling):
4
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for other interspecies differences:
2.5
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for intraspecies differences:
10
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for the quality of the whole database:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for remaining uncertainties:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
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:
no DNEL required: short term exposure controlled by conditions for long-term

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.167 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
DNEL value:
100 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for differences in duration of exposure:
6
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for interspecies differences (allometric scaling):
4
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for other interspecies differences:
2.5
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for intraspecies differences:
10
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for the quality of the whole database:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
AF for remaining uncertainties:
1
Justification:
Default value according to Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Acute toxicity

ECHA Guidance R.8 (Chapter R.8.1.2.5) indicates that DNELs for acute toxicity are not required if no acute toxicity hazard leading to classification has been identified. The substance 2,5-Furandione, dihydro-, mono-C15-20-alkenyl derivs. is not found to be acutely toxic following oral or dermal exposure (LD50 >2000 mg/kg bw) while a low vapour pressure precludes inhalation exposure indicating a low of concern for this route of exposure. No DNELs for acute toxicity are therefore necessary.

Sensitisation

The substance 2,5-Furandione, dihydro-, mono-C15-20-alkenyl derivs. is classified as sensitizing to skin due to the positive results in a Guinea pig maximization test (GPMT).

ECHA Guidance R.8, Appendix R.8-10, (ECHA, 2010) states that skin sensitisation is generally regarded as a threshold effect and thus it may be very difficult to derive a threshold and to set a DNEL. The general approach for sensitizers therefore involves a qualitative approach where a DNEL is used to judge any remaining/residual risks after the implementation of appropriate risk management measures (RMM) and occupational controls (OC).

The extent of the RMM and OC required is dependent on the intrinsic sensitising potency of the substance.

For results obtained using the GPMT, intrinsic sensitising potency is based on the percentage of positive animals in relation to the induction concentration tested.

Based on the 5% intradermal concentration employed during induction phase and the 50% incidence of sensitisation 2,5-Furandione, dihydro-, mono-C15-20-alkenyl derivs. is therefore regarded as having moderate potency to cause skin sensitisation.

 

Repeated dose toxicity

Inhalation

The lowest effect level for oral repeated dose toxicity was found to be the NOAEL of 100 mg/kg bw/d and thus used for the purposes of DNEL derivation for the inhalation route.

Relevant dose descriptors have been developed for the different endpoints and routes of exposure (see Guidance Document, Chapter R.8, Appendix R.8-2). The values are provided below. For potential inhalation exposures, route-to-route extrapolations from the oral NOAEL value are performed:

To convert oral NOAEL into inhalator in NOAEC, a rat default respiratory volume is used corresponding to the daily duration of human exposure (sRVrat: 1.15 m3/kg bw/24 h).

The corrected inhalation NOAEC for consumers is:

inhalation NOAEC = oral NOAEL * (1/ sRV rat 8h) * (ABS oral rat/ ABS inh rat) * (ABS inh rat / ABS inh human)

inhalation NOAEC= 100 * (1/1.15) * (100/100)

inhalation NOAEC = 87.0 mg/m³

In general ECHA Guidance R.8 suggests a factor 2 for route-to-route extrapolation from oral to inhalation to account for general higher uptake by the lung. However, based on the low vapor pressure, the logP value and the low water solubility this value is not justified. Thus, inhalation is assumed to be low and equal to oral absorption for the purposes of the DNEL calculation.

Additional assessment factors (AF) are applied to derive the DNEL. The AFs were based on the procedures described ECHA Guidance R.8

Long-term DNEL Assessment Factors (Inhalation)

Assessment Factor

Consumer

Differences in metabolic rate per b. w. (allometric scaling)

-

Interspecies remaining differences (toxicodynamic and toxicokinetic)

1.5

Intraspecies differences

10

Duration extrapolation

(sub-acute/sub-chronic/chronic)

6 (sub-acute)

Issues related to dose-response

1

Quality of whole database

1

Overall AF

150

 

Dermal

The lowest effect level for oral repeated dose toxicity was found to be the NOAEL of 100 mg/kg bw/d and thus used for the purposes of DNEL derivation for the inhalation route.

Based on the low vapor pressure, the logP value and the low water solubility the dermal absorption can be regarded as low.

Additional assessment factors (AF) are applied to derive the DNEL. The AFs were based on the procedures described ECHA Guidance R.8

Long-term DNEL Assessment Factors (Dermal)

Assessment Factor

Worker

Differences in metabolic rate per b. w. (allometric scaling)

4

Interspecies remaining differences (toxicodynamic and toxicokinetic)

2.5

Intraspecies differences

10

Duration extrapolation

(sub-acute/sub-chronic/chronic)

6 (subchronic)

Issues related to dose-response

1

Quality of whole database

1

Overall AF

600