Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
12.3 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:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
925 mg/m³
Explanation for the modification of the dose descriptor starting point:

No studies were available for the assessment of the DNEL for long-term inhalative exposure. Therefore, route­to-route extrapolation from an oral short-term (28-day) repeated dose toxicity study was used to derive the DNEL (inhalation, long-term exposure). Corrections for differences in respiratory volumes, oral and inhalative absorption rates, light activity at work and differences between human and experimental exposure conditions were taken into account.

NOAECcorr = NOAELoral * (1/0.38 m³/kg bw/day) * (ABSoral-rat/ABSinhal-human) * (6.7 m³ (8h)/10 m³ (8h)) * (fexpo-rat/fexpo-human)

NOAECcorr: Corrected No-Observed-Adverse-Effect-Concentration

NOAELoral: Oral No-Observed-Adverse-Effect-Level as determined in an adequate study (750 mg/kg bw/day)

Respiratory volumes of workers and test animals: 1/0.38 m³/kg bw/day (2.63 m³/kg bw/day)

ABSoral-rat: Oral absorption rate of rats

ABSinhal-human: Inhalative absorption rate of humans. By default, it is assumed that the oral absorption rate is 50% of that of inhalation absorption.

Light activity at work: 6.7 m³ (8h)/10 m³ (8h) (0.67)

fexpo-rat: Exposure frequency of test animals (7 days/week)

fexpo-human: Exposure frequency of humans (5 days/week). The ratio of the exposure frequencies equates to 1.4.

NOAECcorr = 750 * 2.63 * 0.5 * 0.67 * 1.4 = 925 mg/m³

AF for dose response relationship:
1
Justification:
Default (starting point for DNEL calculation is a NOAEC)
AF for differences in duration of exposure:
6
Justification:
Default (subacute to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (not applicable for the inhalation route)
AF for other interspecies differences:
2.5
Justification:
Default (remaining differences)
AF for intraspecies differences:
5
Justification:
Default (worker)
AF for the quality of the whole database:
1
Justification:
Default (assessment based on adequate and reliable studies)
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:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 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):
300
Dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 050 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No studies were available for the assessment of the DNEL for long-term dermal exposure. Therefore, route­to-route extrapolation from an oral short-term (28-day) repeated dose toxicity study was used to derive the DNEL (dermal, long-term exposure). Corrections for differences in oral and dermal absorption rates and experimental exposure conditions were taken into account.

NOAELdermal = NOAELoral * (ABSoral-rat/ABSdermal-human) * (fexpo-rat/fexpo-human)

NOAELdermal: Corrected dermal No-Observed-Adverse-Effect-Level

NOAELoral: Oral No-Observed-Adverse-Effect-Level as determined in an adequate study (750 mg/kg bw/day)

ABSoral-rat: Oral absorption rate of rats

ABSdermal-human: Dermal absorption rate of humans. By default, it is assumed that oral and dermal absorption rates are equal.

fexpo-rat: Exposure frequency of test animals (7 days/week)

fexpo-human: Exposure frequency of humans (5 days/week). The ratio of the exposure frequencies equates to 1.4.

NOAELdermal = 750 mg/kg bw/day * 1 * 1.4 = 1050 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default (starting point for DNEL calculation is a NOAEL)
AF for differences in duration of exposure:
6
Justification:
Default (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (allometric scaling rat)
AF for other interspecies differences:
2.5
Justification:
Default (remaining differences)
AF for intraspecies differences:
5
Justification:
Default (worker)
AF for the quality of the whole database:
1
Justification:
Default (assessment based on adequate and reliable studies)
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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.18 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:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
326 mg/m³
Explanation for the modification of the dose descriptor starting point:

No studies were available for the assessment of the DNEL for long-term inhalative exposure. Therefore, route­to-route extrapolations from an oral short-term (28-day) repeated dose toxicity study was used to derive the DNEL (inhalation, long-term exposure). Corrections for differences in respiratory volumes and oral and inhalative absorption rates were taken into account.

NOAECcorr = NOAELoral * (1/1.15 m³/kg bw/day) * (ABSoral-rat/ABSinh-human)

NOAECcorr: Corrected No-Observed-Adverse-Effect-Concentration

NOAELoral: Oral No-Observed-Adverse-Effect-Level as determined in an adequate study (750 mg/kg bw/day)

Respiratory volumes of the general population and test animals: 1/1.15 m³/kg bw/day (0.87 m³/kg bw/day)

ABSoral-rat: Oral absorption rate of rats

ABSinhal-human: Inhalative absorption rate of humans. By default, it is assumed that the oral absorption rate is 50% of that of inhalation absorption.

NOAECcorr = 750 * 0.87 * 0.5 = 326 mg/m³

AF for dose response relationship:
1
Justification:
Default (starting point for DNEL calculation is a NOAEC)
AF for differences in duration of exposure:
6
Justification:
Default (subacute to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (not applicable for the inhalation route)
AF for other interspecies differences:
2.5
Justification:
Default (remaining differences)
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default (assessment based on adequate and reliable studies)
AF for remaining uncertainties:
1
Justification:
No remaining uncertanties
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:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 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:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No studies were available for the assessment of the DNEL for long-term dermal exposure. Therefore, route­to-route extrapolations from an oral short-term (28-day) repeated dose toxicity study was used to derive the DNEL (dermal, long-term exposure). Corrections for differences in oral and dermal absorption rates were taken into account.

NOAELdermal = NOAELoral * (ABSoral-rat/ABSdermal-human)

NOAELdermal: Corrected dermal No-Observed-Adverse-Effect-Level

NOAELoral: Oral No-Observed-Adverse-Effect-Level as determined in an adequate study (750 mg/kg bw/day)

ABSoral-rat: Oral absorption rate of rats

ABSdermal-human: Dermal absorption rate of humans. By default, it is assumed that oral and dermal absorption rates are equal.

NOAELdermal = 750 mg/kg bw/day * 1 = 750 mg/kg bw/day

AF for dose response relationship:
1
Justification:
Default (starting point for DNEL calculation is a NOAEL)
AF for differences in duration of exposure:
6
Justification:
Default (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (allometric scaling rat)
AF for other interspecies differences:
2.5
Justification:
Default (remaining differences)
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default (assessment based on adequate and reliable studies)
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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 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:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation is needed as an adequate and reliable oral short-term (28-day) repeated dose toxicity study is available. The study is used to derive the DNEL (oral, long-term exposure).

AF for dose response relationship:
1
Justification:
Default (starting point for DNEL calculation is a NOAEL)
AF for differences in duration of exposure:
6
Justification:
Default (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (allometric scaling rat)
AF for other interspecies differences:
2.5
Justification:
Default (remaining differences)
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default (assessment based on adequate and reliable studies)
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:
low hazard (no threshold derived)

Additional information - General Population