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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
83.38 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):
5
Dose descriptor starting point:
NOAEL
Value:
472.9 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
416.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

472.9 mg/kg bw/d in a rat 2y oral study

--> correct to worker, 8h inhalation:

(472.9 / 0.38) * (6.7 / 10) = 833.8 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 = 833.8 / 2 = 416.9 mg/m3

AF for dose response relationship:
1
Justification:
No assessment factor required.
AF for differences in duration of exposure:
1
Justification:
NOAEL from chronic test data available.
AF for interspecies differences (allometric scaling):
1
Justification:
Included in route-to-route extrapolation.
AF for other interspecies differences:
1
Justification:
See below.
AF for intraspecies differences:
5
Justification:
Default value in accordance with ECHA Guidance R.8
AF for the quality of the whole database:
1
Justification:
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:
236.45 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):
20
Dose descriptor starting point:
NOAEL
Value:
472.9 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
4 729 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-Histidine (- 3.32). 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:
1
Justification:
NOAEL from chronic test data available.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value in accordance with ECHA Guidance R.8
AF for other interspecies differences:
1
Justification:
See below.
AF for intraspecies differences:
5
Justification:
Default value in accordance with ECHA Guidance R.8
AF for the quality of the whole database:
1
Justification:
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:
20.56 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:
472.9 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
205.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

472.9 mg/kg bw/d in a rat 2y oral study

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

(472.9 / 1.15) = 411.2 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 = 411.2 / 2 = 205.6 mg/m3

AF for dose response relationship:
1
Justification:
No assessment factor required.
AF for differences in duration of exposure:
1
Justification:
Chronic study data available.
AF for interspecies differences (allometric scaling):
1
Justification:
Included in route-to-route extrapolation.
AF for other interspecies differences:
1
Justification:
See below.
AF for intraspecies differences:
10
Justification:
Default value ECHA Guidance R.8
AF for the quality of the whole database:
1
Justification:
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:
insufficient hazard data available (further information necessary)
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:
118.2 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:
472.9 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
4 729 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-Histidine (- 3.32). 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 needed.
AF for differences in duration of exposure:
1
Justification:
Chronic study data are available.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value in accordance with ECHA Guidance R.8
AF for other interspecies differences:
1
Justification:
See below.
AF for intraspecies differences:
10
Justification:
Default value in accordance with ECHA Guidance R.8
AF for the quality of the whole database:
1
Justification:
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.8 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:
472.9 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
472.9 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification of the dose descriptor is required.

AF for dose response relationship:
1
Justification:
No assessment factor required.
AF for differences in duration of exposure:
1
Justification:
Chronic study result available.
AF for interspecies differences (allometric scaling):
4
Justification:
Default value in accordance with ECHA Guidance R.8
AF for other interspecies differences:
1
Justification:
See below.
AF for intraspecies differences:
10
Justification:
Default value in accordance with ECHA Guidance R.8
AF for the quality of the whole database:
1
Justification:
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