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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
3.29 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:
247 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. A conservative approach is used by performing a route-to-route extrapolation. Please refer to the discussion.

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:
An extrapolation factor is needed since a subacute study is available.
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
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:
DNEL (Derived No Effect Level)
Value:
9.87 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

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:
1.87 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:
560 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. Taken into account the physico-chemical properties of the substance, dermal absoption is anticipated to be 50 % of oral absorption. For details refer to the discussion.

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:
An extrapolation factor is needed since a subacute study is available.
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:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
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:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General

DNEL derivation for the test substance is performed under consideration of the recommendations of ECHA. 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.

Workers – Hazard via inhalation route

Long term systemic inhalation DNEL, worker

Calculation of dose descriptor

Step 1: Selection of the relevant dose descriptor (starting point):

For risk characterisation an inhalation NOAEC was derived by route to route extrapolation.

The oral NOAEL of 200 mg/kg bw/day, obtained from subacute toxicity testing in rats, was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

Step 2: Modification into a correct starting point:

Standard respiratory volume, human (sRVhuman) for 8 hours: 6.7 m3

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

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

Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 50 %/100 % (default)

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEC (inhalation) for workers:

= 200 mg/kg bw/day x 0.5 x 1/0.38 m3/kg bw/day x (6.7 m3/10 m3) x 1.4

= 247 mg/m3

Step 3: Use of assessment factors: 75

Interspecies: no allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed.

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

AF for differences in duration: 6

In conclusion the long term systemic inhalation DNEL workers was calculated to be 3.29 mg/m³ bw/day.

Short term inhalation DNEL, worker

No study for acute inhalation toxicity is availabe. As the substance is classified as acute toxic (oral) Cat 4 acute inhalation toxicity can not be excluded and acute inhalation DNEL is derived. The acute inhalation DNEL was based on long-term inhalation DNEL. The acute inhalation DNEL was calculated as 3 times the value of the corresponding long-term DNEL (ECHA CSR R.8, 2012). Thus, worker DNEL acute inhalation = 3 x 3.29 mg/m3/day = 9.84 mg/m3.

Local effects

No data on respiratory irritation is available. As the substance is not classified as skin and eye irritating also no adverse effects on respiratory system is expected (in accordance with "Guidance on information requirements and chemical safety assessment, chapter R.8"). Based on the physical parameters a peak exposure is not expected. Thus, no DNEL and no qualitative risk assessment is required.

Workers – Hazard via dermal route

Long term systemic dermal DNEL, worker

Calculation of dose descriptor

Step 1: Selection of the relevant dose descriptor (starting point):

For risk characterisation a dermal NOAEL was derived by route to route extrapolation.

The oral NOAEL of 200 mg/kg bw/day, obtained from subacute repeated dose oral toxicity testing in rats was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

Step 2: Modification into a correct starting point:

Based on the physical chemical properties of the substance (low to moderate water solubility, log Pow value =2.3, high molecular weight) a dermal absorption rate of 50 % through skin was deduced.

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEL (dermal) for workers:

= 200 mg/kg bw/day x 2 x 1.4

= 560 mg/kg bw/day

Step 3: Use of assessment factors: 300

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF (subacute exposure period): 6

In conclusion the long term systemic dermal DNEL workers were calculated to be 1.87 mg/kg bw/day.

Acute short term dermal DNEL, worker

The test material is not classified and labelled for acute dermal toxicity, according to Regulation (EC) No 1272/2008 (CLP). Thus, in accordance with “Guidance on information requirements and chemical safety assessment, chapter R.8: Characterisation of dose (concentration)- response for human health” no DNEL is required.

Worker – Hazard for the eyes

According to the EU (CLP and GHS) criteria for classification and labelling requirements for dangerous substances and preparations the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.

References

(not included as endpoint study record)

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.

- ECHA (2017). Guidance on information requirements and chemical safety assessment.Chapter R.7c: Endpoint specific guidance: Guidance on Toxicokinetics. Version 3.0, June 2017

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

- ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 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
Modified dose descriptor starting point:
NOAEC
Value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. A conservative approach is used by performing a route-to-route extrapolation. Please refer to the discussion.

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:
An extrapolation factor is needed since a subacute study is available.
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:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
10
Justification:
The default value for the relatively homogenous group "general population" is used.
AF for the quality of the whole database:
1
Justification:
The default value for the relatively homogenous group "worker" is used.
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:
DNEL (Derived No Effect Level)
Value:
1.74 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

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:
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):
600
Modified dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. Taken into account the physico-chemical properties of the substance, dermal absoption is anticipated to be 50 % of oral absorption. For details refer to the discussion.

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:
An extrapolation factor is needed since a subacute study is available.
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:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
10
Justification:
The default value for the relatively homogenous group "general population" is used.
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:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

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
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation is required.

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:
An extrapolation factor is needed since a subacute study is available.
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:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
10
Justification:
The default value for the relatively homogenous group "general population" is used.
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:
DNEL (Derived No Effect Level)
Value:
0.99 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General

DNEL derivation for the test substance is performed under consideration of the recommendations of ECHA. 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.

 

General population – Hazard via inhalation route

Long term systemic inhalation DNEL, general population

Calculation of dose descriptor

Step 1: Selection of the relevant dose descriptor (starting point):

For risk characterisation an inhalation NOAEC was derived by route-to-route extrapolation.

The oral NOAEL of 200 mg/kg bw/day, obtained from subacute repeated dose toxicity testing in rats was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

Step 2: Modification into a correct starting point:

Standard respiratory volume of the rat (sRVrat) for 24 hours: 1.15 m3/kg bw

Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 50 %/100 % (default)

Corrected NOAEC (inhalation) for general population:

= 200 mg/kg bw/day x 0.5 x 1/1.15 m3/kg bw/day

= 87 mg/m3

Step 3: Use of assessment factors: 150

Interspecies: Respiratory interspecies differences are fully covered by the modification of the NOAEC

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 6 (chronic study)

In conclusion, long term systemic inhalation DNEL, general population = 0.58 mg/m³.

 

Short term acute inhalation DNEL, general population

No study for acute inhalation toxicity is availabe. As the substance is classified as acute toxic (oral) Cat 4 a acute inhalation toxicity can not be excluded and a cute inhalation DNEL is derived. The acute inhalation DNEL was based on long-term inhalation DNEL. The acute inhalation DNEL was calculated as 3 times the value of the corresponding long-term DNEL (ECHA CSR R.8, 2012). Thus, general population DNEL acute inhalation = 3 x 0.58 mg/m³/day = 1.74 mg/m³.

 

Local effects

No data on respiratory irritation is available. As the substance is not classified as skin and eye irritating also no adverse effects on respiratory system is expected (in accordance with "Guidance on information requirements and chemical safety assessment, chapter R.8"). Based on the physical parameters a peak exposure is not expected. The substance is solid with a very low vapour pressure. Inhalation exposure is regarded negligible as no particles below 125 µm were detected in particle size analysis (see section 4.5). Thus, no DNEL is required.

 

General population – Hazard via dermal route

 

Long term systemic dermal DNEL, general population

Calculation of dose descriptor

Step 1: Selection of the relevant dose descriptor (starting point):

For risk characterisation a dermal NOAEL was derived by route to route extrapolation.

The oral NOAEL of 200 mg/kg bw/day, obtained from subacute repeated dose oral toxicity testing in rats was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

Step 2: Modification into a correct starting point:

Based on the physical chemical properties of the substance (low to moderate water solubility, log Pow value = 2.3) a dermal absorption rate of 50 % through skin was deduced.

In conclusion, dermal NOAEL = oral NOAEL x [ABS oral rat/ABS dermal human] = 200 mg/kg bw/day x (100/50) = 400 mg/kg bw/day.

Step 3: Use of assessment factors: 600

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 6 (subchronic to chronic)

 

In conclusion, long term systemic dermal DNEL, general population = 0.66 mg/kg bw/day 

Acute short term dermal DNEL, general population

The test material is not classified and labelled for acute dermal toxicity, according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776. Thus, in accordance with “Guidance on information requirements and chemical safety assessment, chapter R.8: Characterisation of dose (concentration)- response for human health” no DNEL is required.

 

General population – Hazard via oral route

 

Long term systemic oral DNEL, general population

Step 1: Selection of the relevant dose descriptor (starting point):

A subacute oral study in rats is selected for DNEL derivation as it is the relevant repeated dose study performed. In this study, the oral NOAEL in rats is 200 mg/kg bw/day.

Step 2: Modification of the starting point:

Not required.

Step 3: Use of assessment factors: 600

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 6 (subchronic to chronic)

In conclusion, long term systemic oral DNEL, general population = 0.33 mg/kg bw/day

Acute short term oral DNEL, general population

As the substance is classified as acute toxic (oral) Cat 4 acute oral toxicity can not be excluded and acute oral DNEL is derived. The acute oral DNEL was based on long-term oral DNEL. The acute oral DNEL was calculated as 3 times the value of the corresponding long-term DNEL (ECHA CSR R.8, 2012). Thus, worker DNEL acute oral = 3 x 0.33 mg/m³/day =0.99 mg/m³.

 

General population – Hazard for the eyes

According to the EU (CLP and GHS) criteria for classification and labelling requirements for dangerous substances and preparations the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.

References

(not included as endpoint study record)

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.

- ECHA (2017). Guidance on information requirements and chemical safety assessment.Chapter R.7c: Endpoint specific guidance: Guidance on Toxicokinetics. Version 3.0, June 2017

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

-ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016