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Registration Dossier
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EC number: 200-745-3 | CAS number: 71-00-1
Toxicological Summary
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
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
