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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.58 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
129 mg/m³
Explanation for the modification of the dose descriptor starting point:
No long term inhalation study is available therefore route to route extrapolation has been used.
AF for dose response relationship:
1
Justification:
This is a default assessment factor for using the NOAEL as the result. This assessment factor was used based on guidance documents released by the ECHA.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor based upon the ECHAs guidance. In this case the assessment factor is 2 as we have a 6 month dog study which is classed as a sub-chronic study.
AF for interspecies differences (allometric scaling):
1
Justification:
This has been set to a default value of 1 as the inter species variability has already been looked into while calculating the modified dose descriptor.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor used, the value was obtained from guidance documents released by the ECHA
AF for intraspecies differences:
5
Justification:
This is the default assessment factor for looking into intraspecies differences, this assessment factor was obtained from ECHA's guidance and is applicable just for workers.
AF for the quality of the whole database:
2
Justification:
A klimisch reliability of 2 was assigned to the study based on the klimisch reliability scale (the reason a reliability of 2 was used is due to read across). This assessment factor has been based upon guidance documents from the ECHA. The reason we are using an assessment factor of 2 is due to the use of read across.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties, therefore a default assessment factor of 1 can be used.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
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:
0.2 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):
70
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
route to route extrapolation has been used as we have no long term data available via the dermal route of exposure
AF for dose response relationship:
1
Justification:
This is a default assessment factor for using the NOAEL as the result. This assessment factor was used based on guidance documents released by the ECHA.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor based upon the ECHAs guidance. In this case the assessment factor is 2 as we have a 6 month dog study which is classed as a sub-chronic study.
AF for interspecies differences (allometric scaling):
1.4
Justification:
default assessment factor based on allometric scaling for dogs
AF for other interspecies differences:
2.5
Justification:
Default assessment factor used, the value was obtained from guidance documents released by the ECHA
AF for intraspecies differences:
5
Justification:
This is the default assessment factor for looking into intraspecies differences, this assessment factor was obtained from ECHA's guidance and is applicable just for workers.
AF for the quality of the whole database:
2
Justification:
A klimisch reliability of 2 was assigned to the study based on the klimisch reliability scale (the reason a reliability of 2 was used is due to read across). This assessment factor has been based upon guidance documents from the ECHA. The reason we are using an assessment factor of 2 is due to the use of read across.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties, therefore a default assessment factor of 1 can be used.
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

DNEL for workers:

Systemic long term Inhalation DNEL:

Respiratory uptake is anticipated to be unlikely, it doesn't seem pertinent given particle size.

The Mass Median Aerodynamic Diameter has been shown to be 32.724µm and 6.90% of the substance was seen to be in the typical respirable dust range < 10.00 μm. In view of the physical nature of the test item, its apparent low volatility and its’ tendency to clump, it is considered unlikely to represent a significant hazard by the inhalation route.

It should be proposed that the inhalatory absorption value should be 10% on account of the particle size. For the sake of calculation, the inhalatory absorption should not however be considered less than the assumed oral absorption to avoid magnification of the corrected NOAEC, and as such for the purposes of this calculation 50% has been assumed to give a more protective/conservative value.

It is also worthy of note that the point of departure of 50 mg/kg/day is a minimum NOAEL. No higher dose level was selected for testing. Therefore the actual NOAEL may be equal to or greater than 50 mg/kg/day.

The 8h Respiratory Volume was calculated using a value referenced from a European Medicines Agency guidance document which states that the beagle respiratory volume was 9000 L/day, their reported weight was 11.5kg. Using these values a daily respiratory volume can be calculated to be 0.7826m3/kg bw/d and thus the 8h RV = 0.26 m3/kg bw.

Using the equation from guidance document R.8 example B.3 :

corrected inhalatory NOAEC = 50 x (1/0.26) x (50/50) x (6.7/10) = 129mg/m3

therefore DNEL = 129 / ( 1 x 2 x 1 x 2.5 x 5 x 2 x 1 ) = 129 / 50 = 2.58 mg/m3

Inhalation - Systemic acute:

The material is not classified for acute effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

Inhalation - Local long term:

The test item is not a skin sensitiser, skin irritant or eye irritant, therefore the DNEL for local effects is not required.

Inhalation - Local acute:

The test item is not a skin sensitiser, skin irritant or eye irritant, therefore the DNEL for local effects is not required.

Dermal:

Systemic long term:

NOAEL calculated as described in guidance R.8 example B.5 assuming 50% and 50% absorption via oral and dermal routes respectively. The above assessment factors were used to calculate a DNEL of 0.2 mg/kg bw

Dermal - Systemic acute:

The material is not classified for acute effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

Dermal - Local effects - long term:

The test item is not a skin sensitiser, skin irritant or eye irritant, therefore the DNEL for local effects is not required.

Dermal - Local effects - acute:

The test item is not a skin sensitiser, skin irritant or eye irritant, therefore the DNEL for local effects is not required.

Hazard for the eyes - Local effects:

The substance is not classified for eye irritation and therefore the DNEL has not been calculated.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.64 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):
100
Modified dose descriptor starting point:
NOAEC
Value:
64 mg/m³
Explanation for the modification of the dose descriptor starting point:
No long term inhalation study is available therefore route to route extrapolation has been used.
AF for dose response relationship:
1
Justification:
This is a default assessment factor for using the NOAEL as the result. This assessment factor was used based on guidance documents released by the ECHA.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor based upon the ECHAs guidance. In this case the assessment factor is 2 as we have a 6 month dog study which is classed as a sub-chronic study.
AF for interspecies differences (allometric scaling):
1
Justification:
This has been set to a default value of 1 as the inter species variability has already been looked into while calculating the modified dose descriptor.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor used, the value was obtained from guidance documents released by the ECHA
AF for intraspecies differences:
10
Justification:
This is the default assessment factor for the general population, this value has been obtained from the ECHA's guidance documents.
AF for the quality of the whole database:
2
Justification:
A klimisch reliability of 2 was assigned to the study based on the klimisch reliability scale (the reason a reliability of 2 was used is due to read across). This assessment factor has been based upon guidance documents from the ECHA. The reason we are using an assessment factor of 2 is due to the use of read across.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties, therefore a default assessment factor of 1 can be used.
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:
0.36 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):
140
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
route to route extrapolation has been used as we have no long term data available via the dermal route of exposure
AF for dose response relationship:
1
Justification:
This is a default assessment factor for using the NOAEL as the result. This assessment factor was used based on guidance documents released by the ECHA.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor based upon the ECHAs guidance. In this case the assessment factor is 2 as we have a 6 month dog study which is classed as a sub-chronic study.
AF for interspecies differences (allometric scaling):
1.4
Justification:
default assessment factor based on allometric scaling for dogs
AF for other interspecies differences:
2.5
Justification:
Default assessment factor used, the value was obtained from guidance documents released by the ECHA
AF for intraspecies differences:
10
Justification:
This is the default assessment factor for the general population, this value has been obtained from the ECHA's guidance documents.
AF for the quality of the whole database:
2
Justification:
A klimisch reliability of 2 was assigned to the study based on the klimisch reliability scale (the reason a reliability of 2 was used is due to read across). This assessment factor has been based upon guidance documents from the ECHA. The reason we are using an assessment factor of 2 is due to the use of read across.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties, therefore a default assessment factor of 1 can be used.
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:
0.36 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):
140
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route to route extrapolation was not required as we have a long term
AF for dose response relationship:
1
Justification:
This is a default assessment factor for using the NOAEL as the result. This assessment factor was used based on guidance documents released by the ECHA.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor based upon the ECHAs guidance. In this case the assessment factor is 2 as we have a 6 month dog study which is classed as a sub-chronic study.
AF for interspecies differences (allometric scaling):
1.4
Justification:
default assessment factor based on allometric scaling for dogs
AF for other interspecies differences:
2.5
Justification:
Default assessment factor used, the value was obtained from guidance documents released by the ECHA
AF for intraspecies differences:
10
Justification:
This is the default assessment factor for the general population, this value has been obtained from the ECHA's guidance documents.
AF for the quality of the whole database:
2
Justification:
A klimisch reliability of 2 was assigned to the study based on the klimisch reliability scale (the reason a reliability of 2 was used is due to read across). This assessment factor has been based upon guidance documents from the ECHA. The reason we are using an assessment factor of 2 is due to the use of read across.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties, therefore a default assessment factor of 1 can be used.
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

DNEL for general public:

Inhalation:

Inhalation - Systemic long term

Respiratory uptake is anticipated to be unlikely, it doesn't seem pertinent given particle size.

The Mass Median Aerodynamic Diameter has been shown to be 32.724µm and 6.90% of the substance was seen to be in the typical respirable dust range < 10.00 μm. In view of the physical nature of the test item, its apparent low volatility and its’ tendency to clump, it is considered unlikely to represent a significant hazard by the inhalation route.

It should be proposed that the inhalatory absorption value should be 10% on account of the particle size. For the sake of calculation, the inhalatory absorption should not however be considered less than the assumed oral absorption to avoid magnification of the corrected NOAEC, and as such for the purposes of this calculation 50% has been assumed to give a more protective/conservative value.

It is also worthy of note that the point of departure of 50 mg/kg/day is a minimum NOAEL. No higher dose level was selected for testing. Therefore the actual NOAEL may be equal to or greater than 50 mg/kg/day.

The 8h Respiratory Volume was calculated using a value referenced from a European Medicines Agency guidance document which states that the beagle respiratory volume was 9000 L/day, their reported weight was 11.5kg. Using these values a daily respiratory volume can be calculated to be 0.7826m3/kg bw/d and thus the 24h RV = 0.78 m3/kg bw.

Using the equation from guidance document R.8 example B.3 :

corrected inhalatory NOAEC = 50 x (1/0.78) x (50/50) = 64 mg/m3

Therefore DNEL = 64 / ( 1 x 2 x 1 x 2.5 x 10 x 2 x 1 ) = 64 / 100 = 2.58 mg/m3

Inhalation - Systemic acute:

The material is not classified for acute effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

Inhalation - Local long term:

The test item is not a skin sensitiser, skin irritant or eye irritant, therefore the DNEL for local effects is not required.

Inhalation - Local acute:

The test item is not a skin sensitiser, skin irritant or eye irritant, therefore the DNEL for local effects is not required.

Dermal:

Dermal - Systemic long term:

NOAEL calculated as described in guidance R.8 example 8.5 assuming 50% and 50% absorption via oral and dermal routes respectively. The above assessment factors were used to calculate a DNEL of 0.36 mg/kg bw.

Dermal - Systemic acute:

The material is not classified for acute effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

Dermal - Local effects - long term:

The test item is not a skin sensitiser, skin irritant or eye irritant, therefore the DNEL for local effects is not required.

Dermal - Local effects - acute:

The test item is not a skin sensitiser, skin irritant or eye irritant, therefore the DNEL for local effects is not required.

Oral

Oral - systemic - long term:

The NOAEL was provided by a 6 month dog study. The above assessment factors were used to provide a final DNEL of 0.36 mg/kg/bw/day.

Oral - Systemic - acute effects:

The material is not classified for acute systemic effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

Hazard for the eyes - Local effects:

The substance is not classified for eye irritation and therefore the DNEL has not been calculated.