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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
4.7 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
Dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
352.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

For the calculation of the DNEL the NOAEL of 400 mg/kg bw/day obtained from the reproduction / developmental toxicity screening study in Wistar rats (2011) was used to calculate the inhalatory NOAEC. Therefore, the oral NOAEL was calculated using the default respiratory volume for the rat (0.2 l/min/rat) taking into account the difference between metabolic rate scaling and body weight scaling for rats and humans (allometric scaling factor 4) for an eight hour exposure period.

Oral absorption of the rat and inhalatory absorption of humans was assumed to be both 100%. However, in the absence of information concerning absorption, worst case assumptions have to be made. Therefore, a limited absorption for the starting route leading to a low (conservative) internal NOAEL and maximum absorption for the end route leading to a low external NOAEL shall be assumed. Thus, a default factor of 2 shall be applied.

For workers, the resulting air concentration was additionally corrected for the differences between basal caloric demand (6.7 m³) and caloric demand under light activity (10 m³). This correction factor derives from the inhalative volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity). Therefore, the corrected inhalatory NOAEC was calculated as follows:

corrected inhalatory NOAEC = 400 mg/kg * 1 / 0.38 m³/kg bw * 100% / 100% * 6.7 m³/person / 10 m³/person = 705.3 mg/m³ / 2 = 352.6 mg/m³

AF for dose response relationship:
1
Justification:
A corrected inhalatory NOAEC was available and thus, no uncertainties in the dose descriptor were assumed.
AF for differences in duration of exposure:
6
Justification:
The default assessment value of six was chosen to account for differences in the exposure duration from sub-acute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Differences in metabolic rate were already considered in the calculation of the corrected inhalatory NOAEC
AF for other interspecies differences:
2.5
Justification:
Since no studies on toxicokinetics were available, an additional factor of 2.5 for other interspecies differences, such as toxicokinetic differences that are not related to metabolic rate and toxicodynamic differences, was taken into account.
AF for intraspecies differences:
5
Justification:
Default assessment factor taking into account differences in the sensitivity to toxicants in humans (worker).
AF for the quality of the whole database:
1
Justification:
No data gaps have been identified and available information was considered sufficient to meet the tonnage driven data requirements.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties were identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
1.25 mg/m³
DNEL related information
DNEL derivation method:
other: (Technical Rules for Hazardous Substances) TRGS 900
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:
13.3 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
Dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
4 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the calculation of the DNEL the NOAEL of 400 mg/kg bw/day obtained from the reproduction/developmental toxicity screening study in Wistar rats (2011) was used to calculate the dermal NOAEL. Oral absorption of the rat was assumed to be 100%, whereas dermal absorption was suggested to be 10% due to a molecular weight of the test substance greater than 500 g/mol (545 g/mol ) and a log P value that was only marginally in the range between -1 and 4 ( ≤ -0.9).

Therefore, the corrected dermal NOAEL was calculated as follows:

corrected dermal NOAEL = 400 mg/kg * 100% / 10% = 4,000 mg/m³

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

1. Identification of relevant dose descriptor

In a 28 d reproduction/developmental toxicity screening study of an analogue substance (methylated) performed in rat (OECD guideline 421), the substance did not cause mortalities, signs of toxicity or changes in body weight or food consumption. The NOAEL is considered to be 400 mg/kg bw/d in males (lower NOAEL, used for calculation of DNEL).

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

3. Application of assessment factors

Allometric scaling: rat to human = 4

Interspecies factor (remaining differences): 2.5

Intraspecies factor: worker = 5, general population = 10

Exposure duration subacute to chronic: 6

Quality of data base: 1

Dose response: 1

10% dermal absorption due to a molecular weight > 500 g/mol and a log Pow > 4 (factor = 0.1)

4. Daily exposure

Worker: exposed for 8h

General population: exposed for 24h

Calculation of DNEL bases upon Guidance Document on Dermal Absorption, European Commission, 2004 and Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, may 2008

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.16 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
Dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
174 mg/m³
Explanation for the modification of the dose descriptor starting point:

For the calculation of the DNEL the NOAEL of 400 mg/kg bw/day obtained from the reproduction / developmental toxicity screening study in Wistar rats (2011) was used to calculate the inhalatory NOAEC. Therefore, the oral NOAEL was calculated using the default respiratory volume for the rat (0.2 l/min/rat) taking into account the difference between metabolic rate scaling and body weight scaling for rats and humans (allometric scaling factor 4) for a 24-hour exposure period (1.15 m³/kg bw).

Oral absorption of the rat and inhalatory absorption of humans was assumed to be both 100%. However, in the absence of information concerning absorption, worst case assumptions have to be made. Therefore, a limited absorption for the starting route leading to a low (conservative) internal NOAEL and maximum absorption for the end route leading to a low external NOAEL shall be assumed. Thus, a default factor of 2 shall be applied.

Therefore, the corrected inhalatory NOAEC was calculated as follows:

corrected inhalatory NOAEC = 400 mg/kg * 1 / 1.15 m³/kg bw * 100% / 100% = 347.8 mg/m³ / 2 = 174.0 mg/m³

AF for dose response relationship:
1
Justification:
A corrected inhalatory NOAEC was available and thus, no uncertainties in the dose descriptor were assumed.
AF for differences in duration of exposure:
6
Justification:
The default assessment value of six was chosen to account for differences in the exposure duration from sub-acute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Differences in metabolic rate were already considered in the calculation of the corrected inhalatory NOAEC
AF for other interspecies differences:
2.5
Justification:
Since no studies on toxicokinetics were available, an additional factor of 2.5 for other interspecies differences, such as toxicokinetic differences that are not related to metabolic rate and toxicodynamic differences, was taken into account.
AF for intraspecies differences:
10
Justification:
Default assessment factor taking into account differences in the sensitivity to toxicants in humans (general population).
AF for the quality of the whole database:
1
Justification:
No data gaps have been identified and available information was considered sufficient to meet the tonnage driven data requirements.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties were identified.
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:
6.7 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
Dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
4 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the calculation of the DNEL the NOAEL of 400 mg/kg bw/day obtained from the reproduction/developmental toxicity screening study in Wistar rats (2011) was used to calculate the dermal NOAEL. Oral absorption of the rat was assumed to be 100%, whereas dermal absorption was suggested to be 10% due to a molecular weight of the test substance greater than 500 g/mol and a log Pow greater than 4 (factor = 0.1).

Therefore, the corrected dermal NOAEL was calculated as follows:

corrected dermal NOAEL = 400 mg/kg * 100% / 10% = 4,000 mg/m³

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
general population default value
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.67 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
Dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification of the dose descriptor necessary because the available NOAEL was obtained from an oral repeated dose toxicity study.

AF for dose response relationship:
1
Justification:
The available dose descriptor is already a NOAEL and thus, no AF for dose-response relationship has to be applied.
AF for differences in duration of exposure:
6
Justification:
The default assessment value of six was chosen to account for differences in the exposure duration from sub-acute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
The default assessment value for alometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
Since no studies on toxicokinetics were available, an additional factor of 2.5 for other interspecies differences, such as toxicokinetic differences that are not related to metabolic rate and toxicodynamic differences, was taken into account.
AF for intraspecies differences:
10
Justification:
The default assessment value for the general population.
AF for the quality of the whole database:
1
Justification:
No data gaps have been identified and available information was considered sufficient to meet the tonnage driven data requirements.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties were identified.
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

1. Identification of relevant dose descriptor

In a 28 d reproduction/developmental toxicity screening study of an analogue substance (methylated) performed in rat (OECD guideline 421), the substance did not cause mortalities, signs of toxicity or changes in body weight or food consumption. The NOAEL is considered to be 400 mg/kg bw/d in males (lower NOAEL, used for calculation of DNEL).

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

3. Application of assessment factors

Allometric scaling: rat to human = 4

Interspecies factor (remaining differences): 2.5

Intraspecies factor: worker = 5, general population = 10

Exposure duration subacute to chronic: 6

Quality of data base: 1

Dose response: 1

10% dermal absorption due to a molecular weight > 500 g/mol and a log Pow > 4 (factor = 0.1)

4. Daily exposure

Worker: exposed for 8h

General population: exposed for 24h

Calculation of DNEL bases upon Guidance Document on Dermal Absorption, European Commission, 2004 and Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, may 2008