Registration Dossier
Registration Dossier
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EC number: 219-348-1 | CAS number: 2421-28-5
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.6 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):
- 112.5
- Dose descriptor starting point:
- LOAEC
- Value:
- 136 mg/m³
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 68.34 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The exposure in the animal study was for 6h per day an 5 days/week, whereas for workers 8h per day is assumed. Furthermore, it is expected that workers have an increased respiratory volume at light activity (10 m3 per person instead of 6.7 m3 for the general population). Thus, the dose descriptor starting point was corrected for these two points.
corrected LOAEC = inhalatory LOAEC x exp.condition(rat) / exp.condition(human)
corrected LOAEC = inhalatory LOAEC x (6h/d / 8h/d) x (6.7 m3 (8h) / 10 m3 (8h))
corrected LOAEC = 136 mg/m3 x 0.75 x 0.67
corrected LOAEC = 68.34 mg/m3
- AF for dose response relationship:
- 3
- Justification:
- LOAEC to NOAEC
- AF for differences in duration of exposure:
- 6
- Justification:
- subacute to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- not applicable for concentrations
- AF for other interspecies differences:
- 2.5
- Justification:
- pharmacodynamic (remainder)
- AF for intraspecies differences:
- 5
- Justification:
- factor for workers
- AF for the quality of the whole database:
- 1
- Justification:
- standard information available
- AF for remaining uncertainties:
- 0.5
- Justification:
- use of guinea pig which is more sensitive than humans
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.8 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):
- 0.33
- DNEL extrapolated from long term DNEL
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.37 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 150
- Dose descriptor:
- NOAEC
- Value:
- 55 mg/m³
- AF for dose response relationship:
- 1
- Justification:
- NOAEC available
- AF for differences in duration of exposure:
- 12
- Justification:
- 5 days duration
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- not applicable for concentrations
- AF for other interspecies differences:
- 2.5
- Justification:
- pharmacodynamic (remainder)
- AF for intraspecies differences:
- 5
- Justification:
- factor for workers
- AF for the quality of the whole database:
- 1
- Justification:
- standard information available
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.1 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 0.33
- DNEL extrapolated from long term DNEL
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 3 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
For the derivation of the dermal worker DNEL a NOAEL of 300 mg/kg bw/day obtained in an oral 90 -day study in rats (0, 100, 300 and 1000 mg/kg bw) was chosen as dose descriptor starting point.
Calculation of modified dose descriptor starting point:
Corrected dermal NOAEL = oral NOAEL x (ABS oral-rat / ABS dermal-rat) x (ABS dermal-rat / ABS dermal-human)
In absence of detailed information on absorption parameters, a similar dermal and oral absorption is assumend.
This results in the following equation:
Corrected dermal NOAEL = 300 mg/kg x 1 / 1 = 300 mg/kg
- AF for dose response relationship:
- 1
- Justification:
- The descriptor starting point is a NOAEL. The dose response relationship is considered unremarkable.
- AF for differences in duration of exposure:
- 2
- Justification:
- The DNEL is derived from a subchronic repeated dose toxicity study.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default allometric scaling factor for differences between rats and humans.
- AF for other interspecies differences:
- 2.5
- Justification:
- There is no evidence for species differences in the general mode of action or kinetics. However, standard AF is applied.
- AF for intraspecies differences:
- 5
- Justification:
- Default AF for the worker.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole database is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- No further remaining uncertainties.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- sensitisation (skin)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Additional information - workers
DNELs are derived following guidance from ECHA, Guidance for information requirements and the chemical safety assessment, R.8, Characterisation of dose [concentration]-response for human health, 2012.
For species sensitivity issues, see Gad, SC. The Guinea Pig. In: "Animal Models in Toxicology", 2nd Ed., Gad, Shayne C. (Ed.), CRC Press, Boca Raton, FL, 2007, pp. 333 -370.
General Population - Hazard via inhalation 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
DNEL related information
General Population - 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
General Population - Hazard via oral 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
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
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