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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:
0.063 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):
10
Dose descriptor starting point:
LOAEC
Value:
0.63 mg/m³
Explanation for the modification of the dose descriptor starting point:

A LOAEL of 6.3 mg/day has been established based on side effects (hypoglycaemic episodes) after everyday treatment of diabetic persons with inhalation therapy of 6.3 mg human insulin /day. For workers inhaling 10 m3 air/working day this corresponds to a LOAEC of 6.3 mg/day / 10m3/day = 0.63 mg/m3

DNEL = 0.63 mg/m3 / (10 (dose response) x 1 (interspecies) x1 (intraspecies) = 0.063 mg/m3

AF for dose response relationship:
10
Justification:
LOAEC to NOAEC extrapolation. Severe hypoglycaemic episodes have occurred, no indication of a specific NOAEC value.
AF for differences in duration of exposure:
1
Justification:
prolonged inhalation therapy
AF for interspecies differences (allometric scaling):
1
Justification:
human data
AF for other interspecies differences:
1
Justification:
human data
AF for intraspecies differences:
1
Justification:
Diabetic persons are especially sensitive towards hypoglycaemiac episodes from insulin exposure, thus no further factor for workers is justified
AF for the quality of the whole database:
1
AF for remaining uncertainties:
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:
no hazard identified
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 Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

Hazard identification for general population is not relevant as the general population will not be exposed to the the substance that is an intermediate in a pharmaceutical production.