Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
17.28 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:
350 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
432 mg/m³
Explanation for the modification of the dose descriptor starting point:

No long-term toxicity studies via the inhalation route are available for the test substance. Route-to-route extrapolation is performed.


The NOAEL (oral route) observed in a 90-day repeated dose toxicity study performed in rats by Malleshappa (OECD 408; 2022) was used to derive a DNEL long-term, systemic effects via the inhalation route. The No Observed Adverse Effect Level (NOAEL) was established to be 350 mg/kg bw/day. After route-to-route extrapolation from oral to inhalation, the dose descriptor starting point is 432 mg/m³ = 350 mg/kg bw/d x 1/(0.38 m³/kg bw/d) x 6.7 m³/10 m³ x (50%/100%) X (7d/5d) . The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 hours exposure of workers). For workers the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor is derived from the inhaled volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity). In addition, the NOAEL needed to be divided by 2 as the bioavailability via the inhalation route is considered as 100%, while for oral exposure this is only 50%. A correction factor of 7/5 is added for the difference in exposure duration (7 days per week in the in vivo study, 5 days per week for workers).

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point, no additional assessment factor is required
AF for differences in duration of exposure:
2
Justification:
difference in duration, subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
covered by calculation for route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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:
4.9 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
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:
350 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
490 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No long-term dermal toxicity studies are available for the test substance. Route-to-route extrapolation is performed.


The NOAEL (oral route) observed in a 90-day repeated dose toxicity study performed in rats by Malleshappa (OECD 408; 2022) was used to derive a DNEL long-term, systemic effects via the dermal route. The No Observed Adverse Effect Level (NOAEL) was established to be 350 mg/kg bw/day. For the route-to-route extrapolation from oral to dermal, the dose descriptor starting point = 350 mg/kg bw/day x (50%/50%) x (7d/5d) = 490 mg/kg bw/day. A correction factor of 7/5 for differences in exposure duration is added, as animals are exposed 7 days per week during the in vivo study, but workers only 5 days per week. No additional correction factor should be applied as bioavailability after oral and dermal exposure is assumed to be 50%.

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point, no additional assessment factor is required
AF for differences in duration of exposure:
2
Justification:
difference in duration, subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.044 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:
350 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
152.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

No long-term toxicity studies via the inhalation route are available for the test substance. Route-to-route extrapolation is performed.


The NOAEL (oral route) observed in a 90-day repeated dose toxicity study performed in rats by Malleshappa (OECD 408; 2022) was used to derive a DNEL long-term, systemic effects via the inhalation route. The No Observed Adverse Effect Level (NOAEL) was established to be 350 mg/kg bw/day. After route-to-route extrapolation from oral to inhalation, the dose descriptor starting point is 152.2 mg/m³ = 350 mg/kg bw/d x 1/(1.15 m³/kg bw/d) x (50%/100%). The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m³/kg for general population). In addition, the NOAEL needs to be divided by 2 (50%/100%) as the bioavailability via the inhalation route is considered as 100%, while for oral exposure this is only 50%. 

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point, no additional assessment factor is required
AF for differences in duration of exposure:
2
Justification:
difference in duration, subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
covered by calculation for route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.75 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:
350 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
350 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No long-term dermal toxicity studies are available for the test substance. Route-to-route extrapolation is performed.


The NOAEL (oral route) observed in a 90-day repeated dose toxicity study performed in rats by Malleshappa (OECD 408; 2022) was used to derive a DNEL long-term, systemic effects via the dermal route. The No Observed Adverse Effect Level (NOAEL) was established to be 350 mg/kg bw/day. For the route-to-route extrapolation from oral to dermal, the dose descriptor starting point = 350 mg/kg bw/day x (50%/50%) = 350 mg/kg bw/day. No correction factor should be applied as bioavailability after oral and dermal exposure is assumed to be 50%. 


 


 

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point, no additional assessment factor is required
AF for differences in duration of exposure:
2
Justification:
difference in duration, subchronic to chronic

AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.75 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:
350 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
350 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL observed in the subchronic oral toxicity study was used to derive a DNEL long-term, systemic effects via the oral route. The dose descriptor starting point is 350 mg/kg bw/day.


 

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point, no additional assessment factor is required
AF for differences in duration of exposure:
2
Justification:
difference in duration, subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

No consumer use is expected, therefore no hazard assessment for the general population is performed.