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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
137.9 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):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
1 723.75 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 assuming a two times higher absorption via the inhalation route (end route) as compared to the oral route (starting route).
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:
1
Justification:
No extrapolation factor is needed since a chronic 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:
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:
39.4 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):
50
Modified dose descriptor starting point:
NOAEL
Value:
1 970 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated dermal exposure. As a worst case the same dermal absorption as compared to oral is assumed. 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:
1
Justification:
An extrapolation factor is not needed since a chronic 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
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

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 1970 mg/kg bw/day, obtained from chronic 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:

In a first step the oral NOAEL was transferred to humans with a factor of 4 for allometric scaling from rats. For worker a NOEC long-term, inhalation was calculated assuming 70 kg per person, 8h light activity (10 m³ breathing volume), 50 % absorption via oral routes and 100 % absorption via inhalatory routes.

NOEC (Worker)inhalation = 1970 mg/kg bw/day * 1/4 *70 kg * 1/10 m³ * 50%Abs, (oral) / 100 % Abs, (inhal) = 1723.75 mg/m³

Step 3: Use of assessment factors: 12.5

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

In conclusion the long term systemic inhalation DNEL workers was calculated to be 137.9 mg/m³ bw/day.

Short term inhalation DNEL, worker

The test material is not classified and labelled for acute systemic toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Thus, in accordance with “Guidance on information requirements and chemical safety assessment chapter R8: Characterisation of dose (concentration)- response for human health” no DNEL is required.

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 R8"). 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 1970 mg/kg bw/day, obtained from chronic 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:

As a worst case a dermal absorption rate of 100 % through skin was deduced.

In conclusion, dermal NOAEL = oral NOAEL x [ABS oral rat /ABS dermal human] = 1970 mg/kg bw/day x (100/100) = 1970 mg/kg bw/d.

Step 3: Use of assessment factors: 50

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

In conclusion the long term systemic dermal DNEL workers were calculated to be 39.4 mg/kg bw/day.

Acute short term dermal DNEL, worker

The test material is not classified and labelled for acute dermal toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Thus, in accordance with “Guidance on information requirements and chemical safety assessment chapter R8: Characterisation of dose (concentration)- response for human health” no DNEL is required.

Worker – Hazard for the eyes

According to the EU (DSD 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 (2010). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. November 2012.

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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
29.55 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
Modified dose descriptor starting point:
NOAEC
Value:
738.75 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 assuming a two times higher absorption via the inhalation route (end route) as compared to the oral route (starting route).
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:
1
Justification:
No extrapolation factor is needed since a chronic 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:
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:
19.7 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
Modified dose descriptor starting point:
NOAEL
Value:
1 970 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated dermal exposure. As a worst case the dermal absoption is anticipated to be 100 % 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:
1
Justification:
No extrapolation factor is needed since a chronic 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
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:
19.7 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
Modified dose descriptor starting point:
NOAEL
Value:
1 970 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:
1
Justification:
No extrapolation factor is needed since a chronic 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
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 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 1970 mg/kg bw/day, obtained from chronic 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:

In a first step the oral NOAEL was transferred to humans with a factor of 4 for allometric scaling from rats. For general population a NOEC long-term, inhalation was calculated assuming 60 kg per person, 24h light activity (20 m³ breathing volume), 50 % absorption via oral routes and 100 % absorption via inhalatory routes.

 NOEC (General population) inhalation = 1970 mg/kg bw/day * 1/4 *60 kg * 1/20 m³ * 50%Abs, (oral) / 100 % Abs, (inhal) = 738.75 mg/m³

Step 3: Use of assessment factors: 25

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

In conclusion, long term systemic inhalation DNEL, general population = 29.55 mg/m³.

 

Short term acute inhalation, general population

The test material is not classified and labelled for acute oral and dermal toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Thus, in accordance with “Guidance on information requirements and chemical safety assessment chapter R8: Characterisation of dose (concentration)- response for human health” no DNEL is required.

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 R8")

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 1970 mg/kg bw/day, obtained from chronic 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:

As a worst case a dermal absorption rate of 100 % through skin was deduced.

In conclusion, dermal NOAEL = oral NOAEL x [ABS oral rat/ABS dermal human] = 1970 mg/kg bw/day x (100/100) = 1970 mg/kg bw/d.

Step 3: Use of assessment factors: 100

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

 

In conclusion, long term systemic dermal DNEL, general population = 19.7 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 Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Thus, in accordance with “Guidance on information requirements and chemical safety assessment chapter R8: Characterisation of dose (concentration)- response for human health” no DNEL is required. Thus, 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 chronic 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 1970 mg/kg bw/day.

Step 2: Modification of the starting point:

Not required.

Step 3: Use of assessment factors: 100

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

In conclusion, long term systemic oral DNEL, general population = 19.7 mg/kg bw/day

Acute short term oral DNEL, general population

The test material is not classified and labelled for acute systemic toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

General population – Hazard for the eyes

According to the EU (DSD 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 (2010). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. November 2012.

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