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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
70 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: Commission Directive 2006/15/EC established a list of indicative occupational exposure limit (IOEL) values
Dose descriptor starting point:
NOAEL
Value:
342 mg/m³
Explanation for the modification of the dose descriptor starting point:

Expert review and IOEL method

Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
102 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: UK HSE STEL: 2011
Explanation for the modification of the dose descriptor starting point:

Reliable animal data indicate that acetonitrile is not a skin irritant, is not acutely toxic by the dermal route, and is not a skin sensitizer. Local effects are therefore unlikely. However a STEL of 60 ppm (102 mg/m3) is set UK HSE EH40/2005 Workplace exposure limits, 2nd Edition 2011. This may be reflective of early US ACGIH published values for a STEL and is reasonably assumed to be protective of workers for short term exposure.

Local effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
70 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: Commission Directive 2006/15/EC established a list of indicative occupational exposure limit (IOEL) values
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
102 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
20 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: Commission Directive 2006/15/EC established a list of indicative occupational exposure limit (IOEL) values for 8 h inhalation exposure
Dose descriptor starting point:
other: Commission Directive 2006/15/EC established a list of indicative occupational exposure limit (IOEL) values for 8 h inhalation exposure
Value:
70 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The IOEL TWA converted to mg/kg dose over 8 h, breathing 10 m3, then adjusted for 50% dermal absorption

AF for dose response relationship:
1
Justification:
IOEL converted
AF for differences in duration of exposure:
1
Justification:
Chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Worker IOEL converted
AF for other interspecies differences:
1
Justification:
IOEL conversion
AF for intraspecies differences:
1
Justification:
Worker IOEL converted
AF for the quality of the whole database:
1
Justification:
Complete
AF for remaining uncertainties:
1
Justification:
Worker IOEL converted
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:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
340 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
60 mg/m³
Explanation for the modification of the dose descriptor starting point:

A NOAEC in a chronic mouse study is used to calculate a modified dose descriptor. In the chronic mouse study, exposure was for six hours a day for five days a week. To convert this to 24 hour exposure for the general popluation, the NOAEC needs to be corrected by a factor of 0.25 (6/24) and 0.714 (5/7).

The modified dose descriptor is therefore 336 mg/m^3 * 0.25 * 0.714, which is 60 mg/m^3

AF for dose response relationship:
1
Justification:
Default value: A modified NOAEC from a chronic mouse study is used as the starting point.
AF for differences in duration of exposure:
1
Justification:
Since the repeated dose study was a chronic study, no assessment factor for duration of exposure is required.
AF for interspecies differences (allometric scaling):
1
Justification:
This is not required for inhalation as this is accounted for in the calculation
AF for other interspecies differences:
2.5
Justification:
Default value for toxiokinetic and toxicodynamics interspecies differences.
AF for intraspecies differences:
10
Justification:
Default value for the general population.
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default for remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
22 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: Acute Exposure Guidance levels published by EPA.
Overall assessment factor (AF):
3
Dose descriptor starting point:
NOAEC
Value:
66 mg/m³
Modified dose descriptor starting point:
other: Human volunteer study
Explanation for the modification of the dose descriptor starting point:

Not required as taken from human volunteer study (4 h exposure)

AF for dose response relationship:
1
Justification:
Based on human volunteers
AF for interspecies differences (allometric scaling):
1
Justification:
based on human volunteers
AF for other interspecies differences:
1
Justification:
Study conducted in humans; no assessment factor required.
AF for intraspecies differences:
1
Justification:
Based on human volunteers
AF for the quality of the whole database:
1
Justification:
Human exeperience and chronic inhalation studies in animals
AF for remaining uncertainties:
3
Justification:
Limited number of subjects in trial

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
22 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: Acute Exposure Guidance levels 2 published by US EPA.
Overall assessment factor (AF):
3
Dose descriptor starting point:
NOAEC
Value:
66 mg/m³
AF for interspecies differences (allometric scaling):
1
Justification:
Human volunteers
AF for other interspecies differences:
1
Justification:
Study conducted in humans; no assessment factor required.
AF for intraspecies differences:
1
Justification:
study in human volunteers
AF for the quality of the whole database:
1
Justification:
Human volunteers and chronic rodent inhaltion values
AF for remaining uncertainties:
3
Justification:
Limited number of subjects in trial

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
342 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEC from chronic mouse inhaltion exposure study, converted to equivalent rat exposure level for 24 h over 7 days per week.

AF for dose response relationship:
1
Justification:
inhalation
AF for differences in duration of exposure:
1
Justification:
chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
as guidance
AF for other interspecies differences:
2.5
Justification:
standard residual
AF for intraspecies differences:
10
Justification:
Standard for general population
AF for the quality of the whole database:
1
Justification:
Complete
AF for remaining uncertainties:
1
Justification:
No further AF required; assumed 100% obsorption
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:
0.4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
70 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The mouse 200 ppm NOAEC (6 h per day, 5 days per week) was converted to a continuous exposure. This was multiplied by 1.15 m3/kg bw. This was then divided by 7, to convert from the mouse to human.

AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA values used
AF for other interspecies differences:
2.5
Justification:
ECHA values
AF for intraspecies differences:
10
Justification:
Genral population ECHA default
AF for the quality of the whole database:
1
Justification:
Full data base
AF for remaining uncertainties:
1
Justification:
Full data base
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
500
Dose descriptor starting point:
other: LD10
Value:
300 mg/kg bw/day
AF for dose response relationship:
10
Justification:
The mouse LD 10 was divided by 10 to estimate the NOAEL
AF for other interspecies differences:
10
AF for intraspecies differences:
5

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

No uses which expose the genral population to acetonitrile are supported.

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