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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
11.75 mg/m³
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:
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:

For the calculation of the DNEL the NOAEL of 1000 mg/kg bw/day obtained from the combined 28-day repeated dose toxicity study with the reproduction / developmental toxicity screening test in Wistar rats (2015) 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 = 1000 mg/kg * 1 / 0.38 m³/kg bw * 100% / 100% * 6.7 m³/person / 10 m³/person = 1,763.16 mg/m³ / 2 = 881.6 mg/m³

AF for dose response relationship:
1
Justification:
A corrected inhalation 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 dura-tion from sub-acute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Differences in metabolic rate were already considered in the calcula-tion 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 differ-ences, 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.
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33.3 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
10 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the calculation of the DNEL the NOAEL of 1000 mg/kg bw/day obtained from the combined 28-day repeated dose toxicity study with the reproduction / developmental toxicity screening test in Wistar rats (2015) was used to calculate the dermal NOAEL. Oral absorption of the rat was assumed to be 100%. Dermal absorption is likely to be low, however, no experimental data on toxicokinetics were available. On the assumption that dermal absorption will not be higher than oral absorption and considering the high molecular weight of the substance (726.7 g/mol), dermal absorption was suggested to be 10%.

Therefore, the corrected dermal NOAEL was calculated as follows:

corrected dermal NOAEL = 1000 mg/kg * 100% / 10% = 10,000 mg/m³

AF for dose response relationship:
1
Justification:
A corrected dermal NOAEL 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):
4
Justification:
The default assessment factor for difference in species. Here, the factor from rat to human was used.
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:
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 an OECD 422 study of an analogue substance performed in rats, the substance did not cause mortalities, signs of toxicity or any other changes or abnormalities. The NOEL is considered to be 1000 mg/kg bw/d.

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

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:
no hazard 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:
16.7 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:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
10 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the calculation of the DNEL the NOAEL of 1000 mg/kg bw/day obtained from the combined 28-day repeated dose toxicity study with the reproduction / developmental toxicity screening test in Wistar rats (2015) was used to calculate the dermal NOAEL. Oral absorption of the rat was assumed to be 100%. Dermal absorption is likely to be low, however, no experimental data on toxicokinetics were available. On the assumption that dermal absorption will not be higher than oral absorption and considering the high molecular weight of the substance (726.7 g/mol), dermal absorption was suggested to be 10%.

Therefore, the corrected dermal NOAEL was calculated as follows:

corrected dermal NOAEL = 1000 mg/kg * 100% / 10% = 10,000 mg/m³

AF for dose response relationship:
1
Justification:
A corrected dermal NOAEL 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):
4
Justification:
The default assessment factor for difference in species. Here, the factor from rat to human was used.
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modified dose descriptor

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
Justification:
remaining differences
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
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 an OECD 422 study performed on an analogue substance in rats, the substance did not cause mortalities, signs of toxicity or any other changes or abnormalities. The NOEL is considered to be 1000 mg/kg bw/d.

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

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