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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
600 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: EU indicative occupational exposure limit (8 hour)
Overall assessment factor (AF):
1
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:
1 161 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
1
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

Acute DNELs:

Worker: Production of MEK is in excess of 10 t/y. According to the REACH "Guidance on information requirements and chemical safety assessment, Part B: Hazard Assessment", above 10 t/y, the establishment of acute toxicity DNEL is unnecessary in most cases, as the DNEL based on repeated dose toxicity is normally sufficient to ensure that adverse effects do not occur. Thus, as long term DNELs are available for MEK and MEK is not classified for acute toxicity via any route of exposure, separate acute DNELs were not derived.

Long-term DNELs:

IOEL/OEL

The IOEL value for MEK was available and deemed suitable for derivation of the DNEL.

Reference: COMMISSION DIRECTIVE 2000/39/EC of 8 June 2000 establishing a first list of indicative occupational exposure limit values in implementation of Council Directive 98/24/EC on the protection of the health and safety of workers from the risks related to chemical agents at work.

Starting Dose for DNEL calculation:

600 mg/m3(based on occupational exposure of 8 hours/day, 5 days/week)

Modified dose for DNEL Calculation

Worker – Inhalation = 600 mg/m3(no adjustment required)

Worker – Dermal =600 mg/m3x 10 m3/d/70 kg x 54%/4% (Absorption correction – see absorption data below) = 1161 mg/kg/d;

Assessment Factors– no adjustments required for interspecies, exposure duration, dose response or quality of whole database as DNEL is based on an occupational limit for workers.

Final DNELs = Worker – Inhalation DNEL = 600 mg/m3; Worker – Dermal DNEL =1161 mg/kg/d

Absorption Data

Inhalation: Ibrianiet al., 1989 reported 54% retention from inhalation exposures.

Oral: MEK has a molecular weight of <500 g/mol and a log Kow between 0 and 4; therefore, it is assumed to be well absorbed equivalently by the oral and inhalation route; therefore, oral assumed to be 54%.

Dermal: dermal absorption of MEK, in vivo, was reported to be 4%. (NIOSH, 2002)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
106 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
2
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:
412 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
2
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:
31 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
2
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Acute DNELs - General Population: Similar to above for worker, assessment of acute systemic effects should default to the long term systemic DNELs; MEK not classified as a skin irritant; default to systemic DNEL for inhalation local effects.

Long-term DNELs:

The long-term DNEL for the general population was derived from the worker IOEL

Starting Dose for DNEL calculation:

600 mg/m3(based on occupational exposure of 8 hours/day, 5 days/week) (amortized below for continuous exposure)

Modified dose for DNEL Calculation

General Population – Inhalation = 600 mg/m3x10/6.7x 8/24 x 5/7 (amortized for continuous exposure) = 212 mg/m3

General Population – Oral =212 mg/m3x 20 m3/d/70 kg = 61 mg/kg/d (no adjustment for absorption)

General Population - Dermal =212 mg/m3x 20 m3/d/70 kg x 54%/4% (Absorption correction)= 823.5 mg/kg/d

Assessment Factors (AF)

No adjustments required for interspecies, exposure duration, dose response or quality of whole database as DNEL is based on an occupational limit for workers.

An AF of 2 applied for differences between workers and general population (basis: when extrapolating from animal to human, the recommended AF is 10 for general population and 5 for worker – since the starting dose is amortized for continuous exposure an additional 2 fold AF for differences was considered sufficient)

Final DNELs = General population – Dermal DNEL = 823.5mg/kg/d/2 = 412 mg/kg/d;General population – Inhalation DNEL =212 mg/m3/2 = 106 mg/m3; General population – Oral DNEL = 61mg/kg/d/2 = 31 mg/kg/d