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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:
500 mg/m³
DNEL related information
Overall assessment factor (AF):
1
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
888 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
1
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Acute DNELs:

Worker: Production of IPA 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 IPA and IPA is not classified for acute toxicity via any route of exposure, separate acute DNELs were not derived. Since there are only few and partially only conditionally convincing results concerning the irritant effect of 2-propanol in man and animal, any irritant effect is considered unlikely at this concentration.

Long-term DNELs:

IOEL/OEL

There is no IOEL value for IPA. A German MAK was available and deemed suitable for derivation of the DNEL.

Reference: Deutsche Forschungsgemeinschaft List of MAK and BAT Values 2007 Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area Report No. 43

Translated data:

In animal experiments testing subchronic exposures of at least 500 ml/m³ nasal incrustations were observed in male rats. Since there were no microscopic changes, the toxicological relevance of these results is doubtful. The renal changes also observed in male rats exposed to these concentrations are species- and sex-specific effects. When exposing the animals to 1,500 ml/m³ of 2-propanol, only female mice presented a higher relative liver weight. After chronic exposure of male rats to at least 500 ml/m³, the testicle weights and interstitial cytoadenomas of the testicles were found to be slightly increased. In mice inhaling these concentrations the relative testicle weights were reduced, whereas the absolute and relative liver weights were increased. However, this did not always apply to both sexes. The histological results of these organs were not contributory. For the present, it is difficult to state the human relevance of the partially minimal or sex-specific findings in rats and mice exposed to 500 ml/m³.

'MAK Values and Pregnancy' (examinations on rats, 1989): that inhalation of 400 ml/m³ of 2-propanol presumably does not have any embryotoxic effect has been confirmed by further examinations on another species. 

 

The MAK value of 2-propanol is provisionally lowered to 200 ml/m³ (=500 mg/m3). Since there are only few and partially only conditionally convincing results concerning the irritant effect of 2-propanol in man and animal, any irritant effect is considered unlikely at this concentration.

Starting Dose for DNEL calculation:

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

Modified dose for DNEL Calculation

Worker – Inhalation = 500 mg/m3(no adjustment required)

Worker – Dermal =500 mg/m3x 10 m3/d/70 kg = 71 mg/kg/d; 71 mg/kg/d x 100%/8% (Absorption correction – see absorption data below) = 888 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 = Modified Dose; Worker – Inhalation DNEL = 500 mg/m3; Worker – Dermal DNEL =888 mg/kg/d

Absorption Data

Oral: Oral absorption is nearly 100% as evidenced by the nearly complete lack of radiolabel in feces for up to 168 hours following gavage administration of radiolabeled IPA (see toxicokinetic statement)

Inhalation: IPA 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, inhalation absorption assumed to be 100%.

Dermal: Dermal absorption of IPA is rapid but limited. Following a 4-hour occlusive application 84 to 86% of the applied dose was recovered from the skin and 8 to 9% was lost (presumably to volatilization); thus, approximately 5 to 8% of the applied dose was absorbed systemically (see toxicokinetic statement). For the purpose of the DNEL calculation, dermal absorption was conservatively assumed to be 8%.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
89 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
2
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

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

General Population - Hazard via oral route

Systemic effects

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

General Population - Hazard for the eyes

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; IPA 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 OEL

Starting Dose for DNEL calculation:

500 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 = 500 mg/m3x10/6.7x 8/24 x 5/7 (amortized for continuous exposure) = 178 mg/m3

General Population – Oral =178 mg/m3x 20 m3/d/70 kg = 51 mg/kg/d (no adjustment for absorption)

General Population - Dermal =178 mg/m3x 20 m3/d/70 kg = 51 mg/kg/d; 51 mg/kg/d x 100%/8% (Absorption correction – see above under worker) = 638 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 = Modified Dose; General population – Dermal DNEL = 638mg/kg/d/2 = 319 mg/kg/d;General population – Inhalation DNEL178 mg/m3/2 = 89 mg/m3; General population – Oral DNEL = 51mg/kg/d/2 = 26 mg/kg/d