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EC number: 408-200-3 | CAS number: 63187-91-7 FRESCOLAT MGA
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.7 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 352.63 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- AF for oral-to-inhalation extrapolation = 1. Based on available toxicokinetic information, complete absorption of the substance following oral administration can be assumed. As a consequence, no assessment factor is required for oral-to-inhalation extrapolation.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 6
- Justification:
- ECHA REACH standard AF for sub-acute to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Not used for inhalation results
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA REACH standard AF for "differences not related to calorimetric differences"
- AF for intraspecies differences:
- 5
- Justification:
- ECHA REACH standard AF for intraspecies differences to workers
- AF for the quality of the whole database:
- 1
- Justification:
- no issues with the quality of the data base
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties identified
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.83 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):
- 300
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 250 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Correction to NOAEL based on TK information on absorption. See below.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 6
- Justification:
- ECHA REACH standard AF for sub-acute to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA REACH standard AF for rat to human extrapolation
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA REACH standard AF for "differences not related to calorimetric differences"
- AF for intraspecies differences:
- 5
- Justification:
- ECHA REACH standard AF for intraspecies differences to workers
- AF for the quality of the whole database:
- 1
- Justification:
- no issues with the quality of the whole database
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties identified
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Additional information - workers
Description of the calculation of the NOAEC used for the worker, systemic effects, long-term DNEL for the inhalation route
NOAEL = 200 mg/kg bw/d taken from the 28d-repeated dose toxicity study in rats (oral administration).
NOAEC = NOAEL (mg/kg bw/d) * (1/0.38 m3/kg bw) * (6.7 m3/10 m3)
NOAEC = 200 * (1/0.38) * (6.7/10) = 352.63 mg/m3
Description of the calculation of the NOAEL used for the worker, systemic effects, long-term DNEL for the dermal route
NOAEL = 200 mg/kg bw/d taken from the 28d-repeated dose toxicity study in rats (oral administration).
corr. NOAEL = NOAEL (mg/kg bw/d) * Abs (oral, rat) / Abs (dermal, human)
with:
- Abs (oral, rat) = 100% according to ECHA's Guidance on Information Requirements and Chemical Safety Assessment, Section R7c.12.2.4
- Abs (dermal, human) = 80% as modeled according to the equation by Kroes (Food and Chemical Toxicology 45 (2007) 2533 -2562)
corr. NOAEL = 200*100/80 = 250 mg/kg bw/d
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.16 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 150
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 173.91 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- AF for oral-to-inhalation extrapolation = 1. Based on available toxicokinetic information, complete absorption of the substance following oral administration can be assumed. As a consequence, no assessment factor is required for oral-to-inhalation extrapolation.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 6
- Justification:
- ECHA REACH standard AF for sub-acute to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Not used for inhalation results
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA REACH standard AF for "differences not related to calorimetric differences"
- AF for intraspecies differences:
- 10
- Justification:
- ECHA REACH standard AF for the general population
- AF for the quality of the whole database:
- 1
- Justification:
- no issues with the quality of the whole database
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties identified
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.41 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):
- 600
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 250 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Correction to NOAEL based on TK information on absorption. See below.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 6
- Justification:
- ECHA REACH standard AF for sub-acute to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA REACH standard AF for rat to human extrapolation
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA REACH standard AF for "differences not related to calorimetric differences"
- AF for intraspecies differences:
- 10
- Justification:
- ECHA REACH default AF for the general population
- AF for the quality of the whole database:
- 1
- Justification:
- no issues with the whole database
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties identified
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown (no further information necessary)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.33 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):
- 600
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 200 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No route to route extrapolation. No correction on the NOAEL applied; oral absorption by rat and human are assumed to be equal.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 6
- Justification:
- ECHA REACH standard AF for sub-acute to chronic extrapolation
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- ECHA REACH standard AF for rat to human extrapolation
- AF for other interspecies differences:
- 2.5
- Justification:
- ECHA REACH standard AF for "differences not related to calorimetric differences"
- AF for intraspecies differences:
- 10
- Justification:
- ECHA REACH default AF for the general population
- AF for the quality of the whole database:
- 1
- Justification:
- no issues with the whole database
- AF for remaining uncertainties:
- 1
- Justification:
- no remaining uncertainties identified
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- high hazard (no threshold derived)
Additional information - General Population
Description of the calculation of the NOAEC used for the general population, systemic effects, long-term DNEL for the inhalation route
NOAEL = 200 mg/kg bw/d taken from the 28d-repeated dose toxicity study in rats (oral administration).
NOAEC = NOAEL(mg/kg bw/d) * (1/1.15 m3/kg bw)
NOAEC = 200 * (1/1.15) = 173.91 mg/m3
Description of the calculation of the NOAEL used for the general population, systemic effects, long-term DNEL for the dermal route
NOAEL = 200 mg/kg bw/d taken from the 28d-repeated dose toxicity study in rats (oral administration).
corr. NOAEL = NOAEL (mg/kg bw/d) * Abs (oral, rat) / Abs (dermal, human)
with:
- Abs (oral, rat) = 100% according to ECHA's Guidance on Information Requirements and Chemical Safety Assessment, Section R7c.12.2.4
- Abs (dermal, human) = 80% as modeled according to the equation by Kroes (Food and Chemical Toxicology 45 (2007) 2533 -2562)
corr. NOAEL = 200*100/80 = 250 mg/kg bw/d
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