Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
52.89 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):
10
Dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
537.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

600 mg/kg bw/d in a rat 90d oral study

--> correct to worker, 8h inhalation:

(600 / 0.38) * (6.7 / 10) = 1057 mg/m3

with:

0.38 m3/kg bw = total volume inhaled by a rat per day per kg bw

6.7 m3 / 10 m3 = correction for inhalation rate for a person performing light activity

--> assessment factor of 2, default value for oral-to-inhalation extrapolation:

NOAEC = 1075 / 2 = 537.5 mg/m3

AF for dose response relationship:
1
Justification:
No assessment factor required.
AF for differences in duration of exposure:
2
Justification:
Default value according to ECHA Guidance R8
AF for interspecies differences (allometric scaling):
1
Justification:
Included in route-to-route justification.
AF for other interspecies differences:
1
Justification:
See below.
AF for intraspecies differences:
5
Justification:
Default value according to ECHA Guidance R8
AF for the quality of the whole database:
1
Justification:
No additional assessment factor required, sufficient data of good quality available.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
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:
150 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):
40
Dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
6 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Modification of dose descriptor based on route-to-route extrapolation:

A dermal absorption rate of 10% was selected based on the low log Kow value of L-isoleucine (- 1.72). According to ECHA Guidance on information requirements and chemical safety assessment Chapter R.7c, substances with a log Kow below -1 are not likely to be sufficiently lipophilic to cross the stratum corneum. Therefore, dermal absorption is likely to be low, and a dermal absorption value of 10% is deemed appropriate. 


AF for dose response relationship:
1
Justification:
No assessment factor required.
AF for differences in duration of exposure:
2
Justification:
Default value according to ECHA Guidance R8
AF for interspecies differences (allometric scaling):
4
Justification:
Default value according to ECHA Guidance R8
AF for other interspecies differences:
1
Justification:
See below.
AF for intraspecies differences:
5
Justification:
Default value according to ECHA Guidance R8
AF for the quality of the whole database:
1
Justification:
No additional assessment factor required, sufficient data of good quality available.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
DNEL (Derived No Effect Level)
Value:
13.04 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):
20
Dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
260.87 mg/m³
Explanation for the modification of the dose descriptor starting point:

600 mg/kg bw/d in a rat 90d oral study

--> correct to general population, 24h inhalation:

(600 / 1.15) = 521.7 mg/m3

with:

1.15 m3/kg bw = total volume inhaled by a rat in 24h per kg bw

--> assessment factor of 2, default value for oral-to-inhalation extrapolation:

NOAEC = 521.7 / 2 = 260.87 mg/m3

AF for dose response relationship:
1
Justification:
No assessment factor required.
AF for differences in duration of exposure:
2
Justification:
Default value according to ECHA Guidance R8
AF for interspecies differences (allometric scaling):
1
Justification:
Included in route-to-route justification.
AF for other interspecies differences:
1
Justification:
See below.
AF for intraspecies differences:
10
Justification:
Default value according to ECHA Guidance R8
AF for the quality of the whole database:
1
Justification:
No additional assessment factor required, sufficient data of good quality available.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
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:
75 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):
80
Dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
6 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Modification of dose descriptor based on route-to-route extrapolation:

A dermal absorption rate of 10% was selected based on the low log Kow value of L-isoleucine (- 1.72). According to ECHA Guidance on information requirements and chemical safety assessment Chapter R.7c, substances with a log Kow below -1 are not likely to be sufficiently lipophilic to cross the stratum corneum. Therefore, dermal absorption is likely to be low, and a dermal absorption value of 10% is deemed appropriate.

AF for dose response relationship:
1
Justification:
No assessment factor required.
AF for differences in duration of exposure:
2
Justification:
Default value according to ECHA Guidance R8
AF for interspecies differences (allometric scaling):
4
Justification:
Default value according to ECHA Guidance R8
AF for other interspecies differences:
1
Justification:
See below.
AF for intraspecies differences:
10
Justification:
Default value according to ECHA Guidance R8
AF for the quality of the whole database:
1
Justification:
No additional assessment factor required, sufficient data of good quality available.
AF for remaining uncertainties:
1
Justification:
No remainin uncertainties.
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:
7.5 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):
80
Dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification ot the dose descriptor required.

AF for dose response relationship:
1
Justification:
No assessment factor required.
AF for differences in duration of exposure:
2
Justification:
Default value according to ECHA Guidance R8
AF for interspecies differences (allometric scaling):
4
Justification:
Default value according to ECHA Guidance R8
AF for other interspecies differences:
1
Justification:
See below.
AF for intraspecies differences:
10
Justification:
Default value according to ECHA Guidance R8
AF for the quality of the whole database:
1
Justification:
No additional assessment factor required, sufficient data of good quality available.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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

Categories Display