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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:
209.38 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
DNEL value:
2 500 mg/m³
AF for differences in duration of exposure:
2
Justification:
corrected for subchronic to chronic study
AF for intraspecies differences:
3
Justification:
Default ECETOC value
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 783.5 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
9
Modified dose descriptor starting point:
LOAEC
DNEL value:
25 500 mg/m³
AF for intraspecies differences:
3
Justification:
ECETOC default value
AF for remaining uncertainties:
3
Justification:
adjustment for a LOAEC instead of a NOAEC

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:
19.89 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
DNEL value:
950 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
An inhalation study was the only one available
AF for interspecies differences (allometric scaling):
4
Justification:
default value
AF for intraspecies differences:
3
Justification:
default value
AF for remaining uncertainties:
2
Justification:
correction for aubchronic to chronic study
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
low hazard (no threshold derived)

Additional information - workers

DNEL Derivation for Workers

 

Acute Systemic Inhalation:

 

               The dose descriptor selected was the putative LOAEC value from an acute inhalation study using a limit dose of 25.5 mg/l and a 4 hour exposure. This concentration resulted in no deaths, and clinical signs of narcosis. While this study did not assign an effect level, the single concentration used was determined to be the LOAEC based on signs of reversible narcosis.

 

               DNEL Derivation: 25,500 mg/m3(LOAEC) was adjusted to a 15 minute STEL using Habers law. C13T1= C23T2, C2= cube root ((C13T1)/T2) = cube root ((255003)*4/0.25) = 64255.97 mg/m3. This value was corrected for light work and and an 8 hour work day (64255.97 *0.67) = 43051.49 mg/m3. An adjustment factor of 9 was then applied (3 for Intraspecies, 3 for LOAEC to NOAEC, using ECETOC defaults) for a DNEL of 4783.49 mg/m3.

 

 

Long-Term Systemic Inhalation:

               The dose descriptor was the reproductive/developmental NOAEC from an inhalation OECD 421 study, where 2.5 mg/l was the systemic NOAEC.

 

               DNEL Derivation: 2500 mg/m3(NOAEC) was adjusted from a 6 hour study exposure to an 8-hour workday exposure (2500 *0.75 = 1875 mg/m3). This value was adjusted for light work (1875 *0.67 = 1256 mg/m3) and adjustment factors of 6 were applied (3 for Intraspecies, 2 for subchronic to chronic) for a NOAEL of 209.38 mg/m3.

 

Acute Dermal Exposure: Acute dermal toxicity testing showed no effects at 25.5 ml/kg, the highest dose tested. In addition, as this substance is volatile, no testing is required under REACH. Due to the low dermal toxicity of the substance, a DNEL was not derived.

 

Long Term Dermal Exposure

 

The dose descriptor for dermal exposure was an inhalation OECD 421 reproductive scree, where the reprodcutive/developmental NOEC was 5 mg/l, the highest concentration tested.

 

               DNEL Derivation: 2500 mg/m3(systemic NOAEC) was adjusted for a 6 to 8 hour exposure (2500 * 0.75 = 1875). This was corrected for light work using the standard correction factor of 0.67 (1875*0.67 = 1256.25 mg/m3). This was adjusted for route of exposure with the standard value of 0.38 (1256.25 * 0.38 = 477.37 mg/kg). An adjustment factor of 24 was then applied ( 3 – intraspecies, 4 – allometric scaling and 2 for subchronic to chronic) for a final DNEL of 19.89.

 

 

Acute Oral Exposure: This is not a relevant worker endpoint.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
62.5 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
DNEL value:
2 500 mg/m³
AF for intraspecies differences:
5
Justification:
Default ECETOC value
AF for remaining uncertainties:
2
Justification:
Adjustment for subchronic to chronic study
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 283.73 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
15
Modified dose descriptor starting point:
LOAEC
DNEL value:
25 500 mg/m³
AF for intraspecies differences:
5
Justification:
Default ECETOC value
AF for remaining uncertainties:
3
Justification:
Adjustment for LOAEC to NOAEC

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:
17.97 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 875 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
An inhalation study was the only one available
AF for interspecies differences (allometric scaling):
4
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default ECETOC value
AF for remaining uncertainties:
2
Justification:
Adjustment for subchronic to chronic
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
17.97 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
DNEL value:
2 875 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
An inhalation study was the only one available
AF for interspecies differences (allometric scaling):
4
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default ECETOC value
AF for remaining uncertainties:
2
Justification:
Adjustment for subchronic to chronic study
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

DNEL Derivation for General Population

 

 

Acute Systemic Inhalation:

 

The dose descriptor selected was the putative LOAEC value from an acute inhalation study using a limit dose of 25.5 mg/l and a 4 hour exposure. This concentration resulted in no deaths, and clinical signs of narcosis. While this study did not assign an effect level, the single concentration used was determined to be the LOAEC based on signs of reversible narcosis.

 

               DNEL Derivation: 25,500 mg/m3(LOAEC) was adjusted to a 15 minute STEL using Habers law. C13T1= C23T2, C2= cube root ((C13T1)/T2) = cube root ((255003)*4/0.25) = 64255.97 mg/m3. An adjustment factor of 15 was then applied (5 for Intraspecies, 3 for LOAEC to NOAEC, using ECETOC defaults) for a DNEL of 4283.73 mg/m3.

 

Long-Term Systemic Inhalation:

 

The dose descriptor was the systemic NOAEC from an inhalation OECD 421 study, where 2.5 mg/l was the systemic NOAEC.

 

               DNEL Derivation: 2500 mg/m3(NOAEC) was adjusted from a 6 hour study exposure to a 24 hour day (2500 *0.25 = 625 mg/m3) and an adjustment factor of 10 was applied (5 for Intraspecies, 2 for subchronic to chronic) for a NOAEL of 62.5 mg/m3.

 

Acute Dermal Exposure: Acute dermal toxicity testing showed no effects at 25.5 ml/kg, the highest dose tested. In addition, as this substance is volatile, no testing is required under REACH. Due to the low dermal toxicity of the substance, a DNEL was not derived.

 

Long Term Dermal Exposure

 

The dose descriptor for dermal exposure was an inhalation OECD 421 reproductive scree, where the reprodcutive/developmental NOEC was 5 mg/l, the highest concentration tested.

 

               DNEL Derivation: 2500 mg/m3(systemic NOAEC) was adjusted for the route of exposure using the standard correction factor of 1.15 (2500*1.15 = 2875 mg/kg)/ This was corrected for a 6 hour exposure to a 24 hour exposure (2875 *0.25= 718.75). Adjustment factors of 40 were applied (5 – intraspecies, 4 – allometric scaling and 2 for subchronic to chronic) for a final DNEL of 17.97.

 

 

Acute Oral Exposure: Due to the use in industrial applications, acute oral exposure to the general population is not expected, and an acute oral DNEL was not developed.

 

Long Term Oral Exposure

 

The dose descriptor for dermal exposure was an inhalation OECD 421 reproductive scree, where the reprodcutive/developmental NOEC was 5 mg/l, the highest concentration tested.

 

               

 DNEL Derivation: 2500mg/m3(systemic NOAEC) was adjusted for the route of exposure using the standard correction factor of 1.15 (2500*1.15 = 2875 mg/kg)/ This was corrected for a 6 hour exposure to a 24 hour exposure (2875 *0.25= 718.75). Adjustment factors of 40 were applied (5 – intraspecies, 4 – allometric scaling and 2 for subchronic to chronic) for a final DNEL of 17.97.