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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
9.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Technical Report No. 110
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Value:
176.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated exposure by inhalation. The recommended approach using oral data and assuming the same absorption for inhalation and oral route is used.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
1
Justification:
Interspecies differences including toxicokinetics are fully covered by the allometric scaling. There is no additional evidance for species differences including toxicodynamics. Therefore, no additional factor is used.
AF for intraspecies differences:
3
Justification:
Intraspecies differences of worker are considered to be fully covered by the selected factor.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Technical Report No. 110
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation is necessary since a repeated dose dermal toxicity study is available.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
1
Justification:
Interspecies differences including toxicokinetics are fully covered by the allometric scaling. There is no additional evidance for species differences including toxicodynamics. Therefore, no additional factor is used.
AF for intraspecies differences:
3
Justification:
Intraspecies differences of worker are considered to be fully covered by the selected factor.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General

 

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA REACH Guidance (2010) and ECETOC (2003). In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

Acute- systemic effects:

 

The test item is classified and labelled for acute oral toxicity as cat. 4, H302, according to Regulation (EC) No 1272/2008 (CLP) and as Xn, R22 according to Directive 67/548/EEC (DSD). However, no short-term DNEL for systemic effects after oral exposure is derived since oral exposure of workers is not intended. Since the test item is not classified for acute dermal and inhalation toxicity no short-term DNEL was derived.

 

Acute/short-term and long-term exposure - local effects

 

Skin irritation/corrosion and sensitization: The test item is not classified for skin irritation/corrosion and skin sensitization according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Thus, no local DNEL was derived.

 

Eye irritation: The test item is not classified for eye irritation according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Thus, no local DNEL was derived.

 

Respiratory irritation: No effects on respiratory system were observed after short-term inhalation exposure. Furthermore, the test item has no skin or eye irritation potential. The test item is estimated to be not irritating to the respiratory system and therefore no DNEL was derived.

 

Long-term exposure – systemic effects

 

Inhalation exposure:

The derived worker DNEL (long-term inhalation exposure) is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected). The NOAEL assessed in the 28 day repeated dose oral toxicity study (SLI, 1999) is identified as the relevant dose descriptor.

 

- Modification of the starting point

Relevant dose descriptor (NOAEL): 100 mg/kg bw/day

Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/day

Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / ABSinh-human): 1

Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

 

Corrected inhalatory NOAEC for workers

= 100 mg/kg bw/day × (1 / 0.38 m³/kg bw/day) × 1 × (6.7 m³/10 m³)

= 176.3 mg/m³

 

- Calculation of the worker DNEL

Corrected inhalatory NOAEC for workers: 176.3 mg/m³

Assessment factor for exposure duration (subacute to chronic): 6

Assessment factor for intraspecies differences (worker): 3

 

Worker DNEL (long-term inhalation exposure)

= 176.3 mg/m³ / 18

= 9.8 mg/m³

Dermal exposure:

In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in the 90 day repeated dose dermal toxicity study (CIT, 2007) is identified as the relevant dose descriptor. Considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated as follows:

 

Relevant dose descriptor (NOAEL): 150 mg/kg bw/day

Exposure duration factor (subchronic-to-chronic): 2

Allometric scaling factor (rat-to-human): 4

Assessment factor for intraspecies differences (worker): 3

 

Worker DNEL (long-term dermal exposure)

= 150 mg/kg bw/day / (2 × 4 × 3)

= 6.25 mg/kg bw/day

 

 

References

(not included as endpoint study record)

 

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health.Version 2. ECHA-2010 -G-19 –EN.

 

- ECETOC (2010). Technical Report 110. Guidance on assessment factors to derive a DNEL.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Technical Report No. 110
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
Value:
86.96 mg/m³
Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated exposure by inhalation. The recommended approach using oral data and assuming the same absorption for inhalation and oral route is used.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
1
Justification:
Interspecies differences including toxicokinetics are fully covered by the allometric scaling. There is no additional evidance for species differences including toxicodynamics. Therefore, no additional factor is used.
AF for intraspecies differences:
5
Justification:
Intraspecies differences of general population are considered to be fully covered by the selected factor.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.75 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Technical Report No. 110
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation is necessary since a repeated dose dermal toxicity study is available.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
1
Justification:
Interspecies differences including toxicokinetics are fully covered by the allometric scaling. There is no additional evidance for species differences including toxicodynamics. Therefore, no additional factor is used.
AF for intraspecies differences:
5
Justification:
Intraspecies differences of general population are considered to be fully covered by the selected factor.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.8 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA REACH Guidance and ECETOC Technical Report No. 110
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation is necessary since a repeated dose oral toxicity study is available.
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
1
Justification:
There is no evidence for species differences in the general mode of action or kinetics.
AF for intraspecies differences:
5
Justification:
Intraspecies differences of general population are considered to be fully covered by the selected factor.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General

 

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA REACH Guidance (2010) and ECETOC (2003). In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

Long-term exposure – systemic effects

Inhalation exposure:

The derived general population DNEL (long-term inhalation exposure) is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected). The NOAEL assessed in the 28-day repeated dose oral toxicity study (SLI, 1999) is identified as the relevant dose descriptor.

 

- Modification of the starting point

Relevant dose descriptor (NOAEL): 100 mg/kg bw/day

Standard breathing volume rat (24 h): 1.1.5 m3/kg

Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / ABSinh-human): 1

 

Corrected inhalatory NOAEC for general population

= (100 mg/kg bw/day / 1.15 m3/kg/d *1

= 86.96 mg/m³

 

- Calculation of the general population DNEL

Corrected inhalatory NOAEC for workers: 86.96 mg/m³

Assessment factor for exposure duration (subacute to chronic): 6

Assessment factor for intraspecies differences (general population): 5

 

General population DNEL (long-term inhalation exposure)

= 86.96 mg/m³ / (6 × 5)

= 2.9 mg/m³

Dermal exposure:

In order to derive the general population DNEL (long-term dermal exposure), the NOAEL assessed in the 90-day repeated dose dermal toxicity study (CIT, 2007) is identified as the relevant dose descriptor. Considering the appropriate modification and assessment factors, the general population DNEL (long-term dermal exposure) is calculated as follows:

 

Relevant dose descriptor (NOAEL): 150 mg/kg bw/day

Exposure duration factor (subchronic-to-chronic): 2

Allometric scaling factor (rat-to-human): 4

Assessment factor for intraspecies differences (general population): 5

 

General population DNEL (long-term dermal exposure)

= 150 mg/kg bw/day / (2 × 4 × 5)

= 3.75 mg/kg bw/day

Oral exposure:

The test item is classified and labelled for acute systemic toxicity after oral exposure, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). However, no DNEL is derived since no peak exposure of the general population via oral route is expected.

In order to derive the general population DNEL (long-term oral exposure), the NOAEL assessed in the 28-day repeated dose oral toxicity study (SLI, 1999) is identified as the relevant dose descriptor. Considering the appropriate modification and assessment factors, the general population DNEL (long-term oral exposure) is calculated as follows:

 

Relevant dose descriptor (NOAEL): 100 mg/kg bw/day

Exposure duration factor (subacute-to-chronic): 6

Allometric scaling factor (rat-to-human): 4

Assessment factor for intraspecies differences (general population): 5

 

General population DNEL (long-term dermal exposure)

= 100 mg/kg bw/day / (6 × 4 × 5)

= 0.8 mg/kg bw/day

 

 

References

(not included as endpoint study record)

 

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2. ECHA-2010 -G-19 –EN.

 

- ECETOC (2010). Technical Report 110. Guidance on assessment factors to derive a DNEL.