Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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.
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Reaction mass of 1H-Benzotriazole-1-methanamine, N,N-bis(2-ethylhexyl)-6-methyl- and 2H-Benzotriazole-2-methanamine, N,N-bis(2-ethylhexyl)-5-methyl- and N,N-bis(2-ethylhexyl)-4-methyl-1H-benzotriazole-1-methylamine and 2H-Benzotriazole-2-methanamine, N,N-bis(2-ethylhexyl)-4-methyl- and N,N-bis(2-ethylhexyl)-5-methyl-1H-benzotriazole-1-methylamine
EC number: 939-700-4 | CAS number: -
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.3 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):
- 30
- Dose descriptor starting point:
- NOAEL
- Value:
- 45 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 39.7 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Due to lack of repeated dose toxicity data by the inhalation route, a route to route extrapolation was performed. The NOAEL (oral) is converted into a NOAEC (corrected) in accordance to guidance on information requirements and chemical safety assessment, Chapter R.8, ECHA. The NOAEL (oral) has to be divided by a factor of 0.38 m3/kg body weight and corrected for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).In addition, a default factor of 2 is applied to account for differences in oral and inhalative absorption properties. The corrected starting point is therefore:
NOAEC (corrected) = 45 mg/kg / 0.38 m3/kg x 0.5 x (6.7 m3/10m3) = 39.7 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from subacute to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Allometric scaling is part of the route to route extrapolation
- AF for other interspecies differences:
- 1
- Justification:
- see below
- AF for intraspecies differences:
- 5
- Justification:
- standard factor for worker
- AF for the quality of the whole database:
- 1
- Justification:
- GLP and guideline compliant study
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.4 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):
- 120
- Dose descriptor starting point:
- NOAEL
- Value:
- 45 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 45 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The dermal route is typically covered by oral route information in the absence of data for this administration route. No data on dermal penetration are available. Following a worst case approach, dermal absorption of 100% is assumed. The NOAEL for DNEL derivation is therefore 45 mg/kg body weight.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from subacute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- extrapolation from rat to human
- AF for other interspecies differences:
- 1
- Justification:
- see below
- AF for intraspecies differences:
- 5
- Justification:
- standard factor for worker
- AF for the quality of the whole database:
- 1
- Justification:
- GLP-compliant guideline study
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
Identification of relevant dose descriptor
For the derivation of the DNELs, the combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test in rats was qualified as the most relevant study. The dose descriptor chosen was the NOAEL of 45 mg/kg/day.
Rationale for omitting "Factor 2.5"
According to ECETOC’s “guidance on Assessment Factors to derive a DNEL, Technical Report No. 110”, the application of a factor of 2.5 for ‘remaining uncertainties’ is unjustified. There is evidence that multiplicative association between inter- and intraspecies assessment factors is overly conservative and that the inclusion of a factor for remaining differences is unnecessary. ECETOC further recommends using allometric scaling and the 5th percentile of the human distribution of intraspecies variability. Consequently, the ‘remaining uncertainty’ for interspecies variability is already accounted for by the intraspecies AF (Calabrese, 1985; Hattis et al 1987). This is further supported by results of the ongoing ERASM project which examines studies in rats and mice to determine interspecies differences based on a probabilistic approach. In their recent publication (Escher, 2013), the authors confirmed the ECETOC position regarding the factor of 2.5 for remaining uncertainties (i. e. the factor does not apply). Therefore, the factor of 2.5 for remaining uncertainties is omitted for this risk assessment.
Literature:
- Calabrese EJ, Uncertainty factors and interindividual variation, Regul Toxicol Pharmacol. 1985 Jun;5(2):190-6.
- Hattis D et al, Human variability in susceptibility to toxic chemicals-a preliminary analysis of pharmacokinetic data from normal volunteers, Risk Anal. 1987 Dec;7(4):415-26.
- Escher SE et al, Interspecies extrapolation based on the RepDose database—A probabilistic approach, Toxicology Letters 218 (2013) 159– 165
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.3 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):
- 60
- Dose descriptor starting point:
- NOAEL
- Value:
- 45 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 19.5 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Because no inhalation study is available, a route to route extrapolation was performed. The NOAEL (oral) has to be modified into a NOAEC (corrected) in accordance to guidance on information requirements and chemical safety assessment, Chapter R.8, ECHA. Here, the NOAEL has to be divided by a factor of 1.15 m3/kg body weight. In addition, a default factor of 2 is applied to account for differences in oral and inhalative absorption properties. The corrected starting point is therefore: NOAEC (corrected) = 45 mg/kg / 1.15 m3/kg x 0.5 = 19.5 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from subacute to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Allometric scaling is part of the route to route extrapolation
- AF for other interspecies differences:
- 1
- Justification:
- see below
- AF for intraspecies differences:
- 10
- Justification:
- standard factor for the general population
- AF for the quality of the whole database:
- 1
- Justification:
- GLP and guideline compliant study
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
- DNEL (Derived No Effect Level)
- Value:
- 0.2 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):
- 240
- Dose descriptor starting point:
- NOAEL
- Value:
- 45 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 45 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The dermal route is typically covered by oral route information in the absence of data for this administration route. No data on dermal penetration are available. Following a worst case approach, dermal absorption of 100% is assumed. The NOAEL for DNEL derivation is therefore 45 mg/kg body weight.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from subacute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- extrapolation from rat to humans
- AF for other interspecies differences:
- 1
- Justification:
- see below
- AF for intraspecies differences:
- 10
- Justification:
- standard factor for the general population
- AF for the quality of the whole database:
- 1
- Justification:
- GLP-compliant guideline study
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
- 0.2 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):
- 240
- Dose descriptor starting point:
- NOAEL
- Value:
- 45 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 6
- Justification:
- extrapolation from subacute to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- extrapolation from rat to human
- AF for other interspecies differences:
- 1
- Justification:
- see below
- AF for intraspecies differences:
- 10
- Justification:
- standard factor for the general population
- AF for the quality of the whole database:
- 1
- Justification:
- GLP-compliant guideline study
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
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
Identification of relevant dose descriptor
The dose descriptor chosen is the same as for workers (see above). The NOAEL of 45 mg/kg observed in the combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test in rats was used as starting point to derive the DNELs.
Rationale for omitting "Factor 2.5"
According to ECETOC’s “guidance on Assessment Factors to derive a DNEL, Technical Report No. 110”, the application of a factor of 2.5 for ‘remaining uncertainties’ is unjustified. There is evidence that multiplicative association between inter- and intraspecies assessment factors is overly conservative and that the inclusion of a factor for remaining differences is unnecessary. ECETOC further recommends using allometric scaling and the 5th percentile of the human distribution of intraspecies variability. Consequently, the ‘remaining uncertainty’ for interspecies variability is already accounted for by the intraspecies AF (Calabrese, 1985; Hattis et al 1987). This is further supported by results of the ongoing ERASM project which examines studies in rats and mice to determine interspecies differences based on a probabilistic approach. In their recent publication (Escher, 2013), the authors confirmed the ECETOC position regarding the factor of 2.5 for remaining uncertainties (i. e. the factor does not apply). Therefore, the factor of 2.5 for remaining uncertainties is omitted for this risk assessment.
Literature:
- Calabrese EJ, Uncertainty factors and interindividual variation, Regul Toxicol Pharmacol. 1985 Jun;5(2):190-6.
- Hattis D et al, Human variability in susceptibility to toxic chemicals-a preliminary analysis of pharmacokinetic data from normal volunteers, Risk Anal. 1987 Dec;7(4):415-26.
- Escher SE et al, Interspecies extrapolation based on the RepDose database—A probabilistic approach, Toxicology Letters 218 (2013) 159– 165
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.
