Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.8 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):
25
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
370 mg/m³
Explanation for the modification of the dose descriptor starting point:

Basis for the calculation of the corrected inhalatory No-Observed-Adverse-Effect-Concentration (NOAEC) is a No-Observed-Adverse-Effect-Level (NOAEL) of 300 mg/kg bw/day as determined in a subchronic (90-day) oral repeated dose toxicity study in the rat. Differences in respiratory volumes of laboratory animals and workers, frequency of exposure as well as inhalative and oral absorption rates were accounted for.

Corrected inhalatory NOAEC = NOAELoral, rat x (1/sRVrat) x (ABSoral, rat/ABSinhal., human) x (sRVhuman/wRV) x (fexpo, rat/fexpo, worker)

sRV: Standard respiratory volume

wRV: Respiratory volume of workers (8 h)

ABS: Absorption rate (oral absorption is assumed to be 50% of inhalation absorption as default)

fexpo: Frequency of exposure (rat: 7 days/week; workers: 5 days/week)

Corrected inhalatory NOAEC = 300 x (1/0.38) x 0.5 x (6.7/10) x (7/5) = 370 mg/m3

AF for dose response relationship:
1
Justification:
Starting point is NOAEL or NOAEC.
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic extrapolation.
AF for interspecies differences (allometric scaling):
1
Justification:
Not relevant for inhalatory exposure as already considered in species-specific respiratory volumes.
AF for other interspecies differences:
2.5
Justification:
ECHA default.
AF for intraspecies differences:
5
Justification:
ECHA default for workers.
AF for the quality of the whole database:
1
Justification:
High quality studies used to calculate DNEL.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
4.2 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):
100
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
420 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Basis for the calculation of the corrected dermal No-Observed-Adverse-Effect-Level (NOAEL) is a No-Observed-Adverse-Effect-Level (NOAEL) of 300 mg/kg bw/day as determined in a subchronic (90-day) oral repeated dose toxicity study in the rat. Differences in the frequency of exposure as well as dermal and oral absorption rates were accounted for.

Corrected dermal NOAEL = NOAELoral, rat x (ABSoral, rat/ABSdermal, human) x (fexpo, rat/fexpo, worker)

ABS: Absorption rate (dermal absorption is assumed not to be higher than oral absorption as default)

fexpo: Frequency of exposure (rat: 7 days/week; workers: 5 days/week)

Corrected dermal NOAEL = 300 x 1 x (7/5) = 420 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Starting point is NOAEL or NOAEC.
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default for rat.
AF for other interspecies differences:
2.5
Justification:
ECHA default.
AF for intraspecies differences:
5
Justification:
ECHA default for workers.
AF for the quality of the whole database:
1
Justification:
High quality studies used to calculate DNEL.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.61 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
130 mg/m³
Explanation for the modification of the dose descriptor starting point:

Basis for the calculation of the corrected inhalatory No-Observed-Adverse-Effect-Concentration (NOAEC) is a No-Observed-Adverse-Effect-Level

(NOAEL) of 300 mg/kg bw/day as determined in a subchronic (90-day) oral repeated dose toxicity study in the rat. Differences in respiratory volumes

of laboratory animals and humans as well as inhalative and oral absorption rates were accounted for.

Corrected inhalatory NOAEC = NOAELoral, rat x (1/sRVrat) x (ABSoral, rat/ABSinhal., human)

sRV: Standard respiratory volume

ABS: Absorption rate (oral absorption is assumed to be 50% of inhalation absorption as default)

Corrected inhalatory NOAEC = 300 x (1/1.15) x 0.5 = 130 mg/m3

AF for dose response relationship:
1
Justification:
Starting point is NOAEL or NOAEC.
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic extrapolation.
AF for interspecies differences (allometric scaling):
1
Justification:
Not relevant for inhalatory exposure as already considered in species-specific respiratory volumes.
AF for other interspecies differences:
2.5
Justification:
ECHA default.
AF for intraspecies differences:
10
Justification:
ECHA default for general population.
AF for the quality of the whole database:
1
Justification:
High quality studies used to calculate DNEL.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
1.5 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Basis for the calculation of the corrected dermal No-Observed-Adverse-Effect-Level (NOAEL) is a No-Observed-Adverse-Effect-Level (NOAEL) of 300 mg/kg bw/day as determined in a subchronic (90-day) oral repeated dose toxicity study in the rat. Differences in the dermal and oral absorption rates were accounted for.

Corrected dermal NOAEL = NOAELoral, rat x (ABSoral, rat/ABSdermal, human)

ABS: Absorption rate (dermal absorption is assumed not to be higher than oral absorption as default)

Corrected dermal NOAEL = 300 x 1 = 300 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Starting point is NOAEL or NOAEC.
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default for rat.
AF for other interspecies differences:
2.5
Justification:
ECHA default.
AF for intraspecies differences:
10
Justification:
ECHA default for general population.
AF for the quality of the whole database:
1
Justification:
High quality studies used to calculate DNEL.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
1.5 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation is required as the oral long-term DNEL for systemic effects is based on a No-Observed-Adverse-Effect-Level (NOAEL) of 300 mg/kg bw/day as determined in a subchronic (90-day) oral repeated dose toxicity study in the rat.

AF for dose response relationship:
1
Justification:
Starting point is NOAEL or NOAEC.
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default for rat.
AF for other interspecies differences:
2.5
Justification:
ECHA default.
AF for intraspecies differences:
10
Justification:
ECHA default for general population.
AF for the quality of the whole database:
1
Justification:
High quality studies used to calculate DNEL.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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

Categories Display