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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.26 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
881.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

In accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health" (Figure R. 8-3) the oral - inhalation (route to route) dose descriptor was calculated as follows :-

NOAEC (workers) = NOAEL x [1/0.38] x [0.5 x 1] x 0.67

= 1000 x (2.63 x 0.5 x 0.67)

= 881.6

AF for dose response relationship:
1
Justification:
Default assessment factor for dose response relationship specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic default assessment factor in accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health"; Table R. 8-5.
Justification:
For inhalation, DNELs allometric scaling is not usually applied.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for interspecies "remaining differences" specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for intraspecies differences:
5
Justification:
Default assessment factor for intraspecies specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for the quality of the whole database:
1
Justification:
Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL extrapolated from long term DNEL

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:
10 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default assessment factor for dose response relationship specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic default assessment factor in accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health"; Table R. 8-5.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for rats compared to humans specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-3
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for interspecies "remaining differences" specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for intraspecies differences:
5
Justification:
Default assessment factor for intraspecies specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for the quality of the whole database:
1
Justification:
Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
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

No systemic effects have been observed in rodent studies after short-term and long-term exposure to the substance. The LD50 for acute oral and acute dermal exposure is >2000 mg/kg bw and based on the physical chemical properties and the use of Keroflux ES 3241 an inhalation exposure is unlikely. Thus, derivation of a DNEL for acute / short-term exposure is not appropriate according to Chapter R8 of the ECHA guidance on information requirements and chemical safety assessment (2008).

Keroflux ES 3241 has been tested and is positive for skin sensitization in a guinea-pig maximization test. Because of the single induction dose regime employed the maximization test does not allow to derive a starting point for DNEL derivation. Based on the potency considerations in chapter R8 of the ECHA guidance on information requirements and chemical safety assessment (2008) the substance can be considered rather a moderate skin sensitizer by taking into account the concentration for intradermal induction (> 1%) as well as the incidence of sensitization (> 60%). Since the data available do not allow for a DNEL derivation the operational conditions and risk management measures are installed to ensure that the exposure to the substance is as low as possible.

DNEL - systemic effects for long-term exposure can be derived starting with the NOAEL from the one-generation study (1000 mg/kg bw/d). Since no information on the dermal absorption of the substance is available worst-case assumption of 100% penetration is made for oral to dermal extrapolation. No adverse effects have been observed with regard to systemic toxicity, reproductive toxicity and developmental toxicity. Thus, default factors for allometric scaling, intraspecies variation, remaining differences and time extrapolation are chosen:

Allometric scaling: 4

Intraspecies variation: 5

Remaing differences: 2.5

Time extrapolation (subchronic to chronic): 2

The overall assessment factor of 100 applied to the NOAEL of 1000 mg/kg bw/d results in a DNEL (dermal) for worker of 10 mg/kg bw/d.

Derivation of an inhalation DNEL - systemic effects as well as local effects for long-term exposure is considered not appropriate because of the physicochemical properties and the use of the substance.

Operational conditions and risk management measures installed to minimize risk after a single dermal exposure are considered sufficient to prevent for local effect after long-term exposure.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
60 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
3 000 mg/m³
Explanation for the modification of the dose descriptor starting point:

In accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health" (Figure R. 8.3) the oral - inhalation (route to route) dose descriptor was calculated as follows :-

NOAEC (General Population) = NOAEL x [1/1.15] x [0.5 x 1]

NOAEC (General Population) = 1000 x [1/1.5] x [0.5 x 1]

NOAEC (General Population) = 3000 mg/mg3

AF for dose response relationship:
1
Justification:
Default assessment factor for dose response relationship specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic default assessment factor in accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health"; Table R. 8-5.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for interspecies "remaining differences" specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for intraspecies differences:
10
Justification:
Default assessment factor for intraspecies specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for the quality of the whole database:
1
Justification:
Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
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:
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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default assessment factor for dose response relationship specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic default assessment factor in accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health"; Table R. 8-5.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for rats compared to humans specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-3
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for interspecies "remaining differences" specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for intraspecies differences:
10
Justification:
Default assessment factor for intraspecies specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for the quality of the whole database:
1
Justification:
Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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:
1 000 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for intraspecies differences:
10
Justification:
Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
AF for the quality of the whole database:
1
Justification:
Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6
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

No systemic effects have been observed in rodent studies after short-term and long-term exposure. The LD50 for acute oral and acute dermal exposure is >2000 mg/kg bw and based on the physical chemical properties and the use of the substance in an inhalation exposure is unlikely. Thus, derivation of a DNEL for acute / short-term exposure for all three relevant routes of exposure is not appropriate according to Chapter R8 of the ECHA guidance on information requirements and chemical safety assessment (2008).

The substance has been tested positive for skin sensitization in a guinea-pig maximization test. Because of the single induction dose regime employed the maximization test does not allow to derive a starting point for DNEL derivation. Based on the potency considerations in chapter R8 of the ECHA guidance on information requirements and chemical safety assessment (2008) the substance can be considered a moderate skin sensitizer by taking into account the concentration for intradermal induction (> 1%) as well as the incidence of sensitization (> 60%). Data available does not allow for a DNEL derivation, however use and final concentration of the substance in fuel as well as risk management measures already applied at the gas stations are considered sufficient to minimize risk for local effects after short-term exposure to the substance.

DNEL - systemic effects for long-term exposure can be derived starting with the NOAEL from the one-generation study (1000 mg/kg bw/d). Since no information on the dermal absorption of the substance is available worst-case assumption of 100% penetration is made for oral to dermal extrapolation. No adverse effects have been observed with regard to systemic toxicity, reproductive toxicity and developmental toxicity. Thus, default factors for allometric scaling, intraspecies variation, remaining differences and time extrapolation are chosen:

Allometric scaling: 4

Intraspecies variation: 10

Remaining differences: 2.5

Time extrapolation (subchronic to chronic): 2

The overall assessment factor of 200 is applied to the NOAEL of 1000 mg/kg bw/d results in a DNEL (oral and dermal) for the general population of 5.0 mg/kg bw/d.

Derivation of a inhalation DNEL - systemic effects as well as local effects for long-term exposure is considered not appropriate because of the physicochemical properties and the use of the substance.

Operational conditions and risk management measure installed to minimize risk after a single dermal exposure are considered sufficient to prevent for local effect after long-term exposure.