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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
2.35 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
Value:
176.32 mg/m³
Explanation for the modification of the dose descriptor starting point:
No data are available for the inhalation route. However, reliable data are available for the oral route.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
ECHA default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA default (not applied for inhalation route)
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default (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
DNEL related information

Workers - Hazard via dermal 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No data are available for the dermal route. However, reliable data are available for the oral route.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
ECHA default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default (rat to human)
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default (worker)
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
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

The 28-day oral NOAEL for the substance was determined to be 200 mg/kg bw/day, based on weight of evidence. The NOAEL was based on increase of kidney weight associated with histopathological changes in high dose females (1000 mg/kg bw/day) at the end of the recovery period. The kidney weight at the end of recovery period was of lower statistical significance when compared with the end of dosing period. This is an indication for reversibility of kidney weight change also in female animals. No data on reproductive or developmental toxicity are available.

The substance is not acutely harmful by the oral and dermal routes, not irritating to skin or eyes and not sensitising.

The substance has no local effects.

 

Inhalation DNEL – worker – long term - systemic effects:

The DNEL for systemic effects via the inhalation route is determined on the basis of route-to-route extrapolation from 28-day oral data which had NOAEL = 200 mg/kg bw/day.

 

The following corrections were made to the NOAEL (oral) to derive the NOAEC (inhalation): Assessment factor for route-to-route extrapolation (oral to inhalation): 2 (ECHA default)

Correction for respiratory rate and volume (rat to human worker): (6.7 m³/d / 10 m³/d) * (1 / 0.38 m³/kg) (ECHA default).

Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is:

100 mg/kg/day * (6.7 m³/d / 10 m³/d)*(1 / 0.38 m³/kg) = 176.32 mg/m³.

 

The following assessment factors were applied to the corrected NOAEC:

Assessment factor for extrapolation of exposure duration (sub-acute to chronic): 6 (ECHA default)

Assessment factor for allometric scaling: 1 (ECHA default, not applied for inhalation route)

Assessment factor for other interspecies differences: 2.5 (ECHA default);

Assessment factor for intraspecies differences: 5 (ECHA default, worker).

The overall Assessment factor is therefore: 6 * 1 * 2.5 * 5 = 75

 

The overall DNEL (repeated-dose – systemic – inhalation - worker)is therefore 176.32 mg/m³ / 75 = 2.35 mg/m³.

 

Dermal DNEL – worker – long term - systemic effects:

The DNEL for systemic effects via the dermal route is determined on the basis of route-to route extrapolation from 28-day oral data, which had NOAEL = 200 mg/kg bw/day.

 

The following correction was made to the NOAEL:

Assessment factor for route-to-route extrapolation (oral to dermal): 1 (ECHA default)

The corrected NOAEL for the dermal route is therefore: 200 mg/kg bw/day /1 = 200 mg/kg bw/day.

 

The assessment factors used to determine the DNELs for repeated dose toxicity were selected on the following basis:

Assessment factor for extrapolation of exposure duration (sub-acute to chronic) has been used: 6 (ECHA default)

Assessment factor for allometric scaling (rat to human): 4 (ECHA default)

Assessment factor for other interspecies differences: 2.5 (ECHA default)

Assessment factor for intraspecies differences: 5 (ECHA default, worker)

The overall Assessment factor is therefore: 6 * 4 * 2.5 * 5 = 300

 

The overall DNEL (repeated-dose – systemic – dermal - worker) is therefore 200 mg/kg bw/day / 300 = 0.67 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 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
Value:
200 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
ECHA default (sub-acute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default (rat to human)
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default (general population)
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

There is no consumer exposure to the substance as it is not present in products used by the general population. However, an oral DNEL for the general population is needed for the assessment of exposure to man via the environment.

 

The 28-day oral NOAEL for the substance was determined to be 200 mg/kg bw/day, based on weight of evidence. The NOAEL was based on increase of kidney weight associated with histopathological changes in high dose females (1000 mg/kg bw/day) at the end of the recovery period. The kidney weight at the end of recovery period was of lower statistical significance when compared with the end of dosing period. This is an indication for reversibility of kidney weight change also in female animals. No data on reproductive or developmental toxicity are available.

The substance is not acutely harmful by the oral and dermal routes, not irritating to skin or eyes and not sensitising.

The substance has no local effects.

 

Oral DNEL – general population – long term - systemic effects:

The DNEL for systemic effects via the oral route is determined from 28-day oral data which had NOAEL = 200 mg/kg bw/day.

 

No corrections were made to the NOAEL; therefore, the dose descriptor starting point is 200 mg/kg bw/day.

 

The following assessment factors were applied to the corrected NOAEL:

Assessment factor for extrapolation of exposure duration (sub-acute to chronic): 6 (ECHA default)

Assessment factor for allometric scaling: 4 (ECHA default, rat to human)

Assessment factor for other interspecies differences: 2.5 (ECHA default);

Assessment factor for intraspecies differences: 10 (ECHA default, general population).

The overall Assessment factor is therefore: 6 * 4 * 2.5 * 10 = 600

 

The overall DNEL (repeated-dose – systemic – oral – general population) is therefore 200 mg/kg bw/day / 600 = 0.33 mg/kg bw/day.