Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.8 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:
330 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
581.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected inhalatory NOAEC = oral NOAEL * 1/0.38 m3 kg-1 * 6.7/10

There are no quantitative oral or inhalation absorption rates available. Based on the log Pow in the range of 1.82 -3.72, the high water solubility, and the information that absorption occurs following oral exposure, absorption by the respiratory tract is likely and can be assumed to be in the same range than oral absorption. Therefore, no further factor for absorption differences oral to inhalation is introduced.

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL, the default assessment factor is 1, according to ECHA Guidance.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for duration extrapolation subacute to chronic, according to ECHA Guidance.
AF for interspecies differences (allometric scaling):
1
Justification:
Already covered in the modification of starting point from rat oral to human inhalatory exposure, considering the differences in respiratory volume for rat and human (worker).
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences, according to ECHA Guidance.
AF for intraspecies differences:
5
Justification:
Default factor for intraspecies differences in workers, according to ECHA Guidance.
AF for the quality of the whole database:
1
Justification:
The default factor for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements is 1, according to ECHA Guidance.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
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:
1.1 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:
330 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No further factors is introduced for absorption differences extrapolation oral to dermal, because it can be assumed that absorption after dermal exposure will not be higher than after oral exposure (e.g. molecular weight in a range not favourable for dermal absorption).

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL, the default assessment factor is 1, according to ECHA Guidance.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for duration extrapolation subacute to chronic, according to ECHA Guidance.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling rat to human, according to ECHA Guidance.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences, according to ECHA Guidance.
AF for intraspecies differences:
5
Justification:
Default factor for intraspecies differences in workers, according to ECHA Guidance.
AF for the quality of the whole database:
1
Justification:
The default factor for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements is 1, according to ECHA Guidance.
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

Contact to the skin is the relevant route to be assessed for workers. Inhalation exposure is unlikely, since the vapour pressure of the substance is calculated to be negligible at ambient temperature.

In the available Combined Repeated Dose toxicity study with the Reproduction/ Developmental Toxicity Screening (OECD TG 422) with oral exposure the substance was generally well tolerated by the rats. The kidney was identified as the primary target organ with adverse effects reported in males and females given 1000 mg/kg bw (degeneration of the tubular epithelium in both sexes and tubular basophilia in males). The NOAEL was concluded to be at the next lower dose, i.e. 330 mg/kg bw. This study is used as the point of departion for a DNEL delineation, unless further data will become available (a testing proposal of an OECD TG 408 is included in this dossier).

Since only systemic advers effects were revealed in that study route to route extrapolation from oral to dermal and from oral to inhalation is possible, and is applied (for further explanations and assessment factors see DNEL endpoint-specific fields).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.9 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:
330 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
287 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected inhalatory NOAEC = oral NOAEL * 1/1.15 m3 kg-1

There are no quantitative oral or inhalation absorption rates available. Based on the log Pow in the range of 1.82 -3.72, the high water solubility, and the information that absorption occurs following oral exposure, absorption by the respiratory tract is likely and can be assumed to be in the same range than oral absorption. Therefore, no further factor for absorption differences oral to inhalation is introduced.

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL, the default assessment factor is 1, according to ECHA Guidance.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for duration extrapolation subacute to chronic, according to ECHA Guidance.
AF for interspecies differences (allometric scaling):
1
Justification:
Already covered in the modification of starting point from rat oral to human inhalatory exposure, considering the differences in respiratory volume for rat and human (worker).
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences, according to ECHA Guidance.
AF for intraspecies differences:
10
Justification:
Default factor for intraspecies differences in the general population, according to ECHA Guidance.
AF for the quality of the whole database:
1
Justification:
The default factor for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements is 1, according to ECHA Guidance.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
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:
0.55 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:
330 mg/m³
Explanation for the modification of the dose descriptor starting point:

No further factors is introduced for absorption differences extrapolation oral to dermal, because it can be assumed that absorption after dermal exposure will not be higher than after oral exposure (e.g. molecular weight in a range not favourable for dermal absorption).

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL, the default assessment factor is 1, according to ECHA Guidance.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for duration extrapolation subacute to chronic, according to ECHA Guidance.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling rat to human, according to ECHA Guidance.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences, according to ECHA Guidance.
AF for intraspecies differences:
10
Justification:
Default factor for intraspecies differences in the general population, according to ECHA Guidance.
AF for the quality of the whole database:
1
Justification:
The default factor for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements is 1, according to ECHA Guidance.
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:
0.55 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:
330 mg/kg bw/day
AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL, the default assessment factor is 1, according to ECHA Guidance.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for duration extrapolation subacute to chronic, according to ECHA Guidance.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling rat to human, according to ECHA Guidance.
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining interspecies differences, according to ECHA Guidance.
AF for intraspecies differences:
10
Justification:
Default factor for intraspecies differences in the general population, according to ECHA Guidance.
AF for the quality of the whole database:
1
Justification:
The default factor for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements is 1, according to ECHA Guidance.
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

Oral ingestion and contact to the skin are the relevant routes to be assessed for the general population. Inhalation exposure is unlikely, since the vapour pressure of the substance is calculated to be negligible at ambient temperature.

In the available Combined Repeated Dose toxicity study with the Reproduction/ Developmental Toxicity Screening (OECD TG 422) with oral exposure the substance was generally well tolerated by the rats. The kidney was identified as the primary target organ with adverse effects reported in males and females given 1000 mg/kg bw (degeneration of the tubular epithelium in both sexes and tubular basophilia in males). The NOAEL was concluded to be at the next lower dose, i.e. 330 mg/kg bw. This study is used as the point of departion for a DNEL delineation, unless further data will become available (a testing proposal of an OECD TG 408 is included in this dossier).

Since only systemic advers effects were revealed in that study route to route extrapolation from oral to dermal and from oral to inhalation is possible, and is applied (for further explanations and assessment factors see DNEL endpoint-specific fields).