Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEC
DNEL value:
365 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
183.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

For the correction of the NOAEC the NOAEC should be multiplied by 6/8 to correct for exposure time per day and with 6.7/10 to correct for breathing volume of workers. The “corrected NOAEC” would then be 365 mg/m3* 6/8 * 6.7/10 = 183.4 mg/m3.

AF for dose response relationship:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEC, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
2
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. So, as only a sub-chronic toxicity study is available, default assessment factor of 2 is to be applied, as a standard procedure.
AF for interspecies differences (allometric scaling):
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, as long as route-to-route extrapolation is not needed, allometric scaling should not be applied in cases where doses in experimental animal studies are expressed as concentrations (e.g. in mg/m3 air, ppm in diet, or mg/L in the drinking water) as these are assumed to be already scaled according to the allometric principle, since ventilation rate and food intake directly depend on the basal metabolic rate. In this case the NOAEC is expressed as concentration (mg/m3), therefore a factor for allometric scaling is not needed.
AF for other interspecies differences:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: If no substance-specific data are available, the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part). In case substance-specific information shows specific susceptibility differences between species, which are not related to differences in basal metabolic rate, the additional factor of 2.5 for ‘remaining differences’ should be modified accordingly. In this case the effects are not dependent on metabolic rate or systemic absorption and no further kinetic considerations apply. Therefore, the default factor for remaining uncertainties of 2.5 could be reduced to 1.
AF for intraspecies differences:
5
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: If the dose descriptor (e.g. N(L)OAEL, benchmark dose, etc.) has been derived from an animal study, animal intraspecies variation/differences has already to some extent been accounted for in that dose descriptor. Ideally therefore, the intraspecies factor should reflect the additional interspecies variability, i.e. the difference between variability in the human population and variability in the animal population.For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill.
AF for the quality of the whole database:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.
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:
DNEL (Derived No Effect Level)
Value:
10.7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
NOAEC
DNEL value:
53.3 mg/m³
AF for dose response relationship:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEC, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: A factor allowing for differences in the experimental exposure duration and the duration of exposure for the population and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. However, a correction for exposure duration for the inhalation rat study (14 weeks) is not appropriate as the local effects are mainly driven by the exposure concentration. The local corrosive effect of amines is expected to set immediately, without time-dependent worsening. Therefore, the default assessment factor of 2 is not applied in this instance.
AF for interspecies differences (allometric scaling):
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, as long as route-to-route extrapolation is not needed, allometric scaling should not be applied in cases where doses in experimental animal studies are expressed as concentrations (e.g. in mg/m3 air, ppm in diet, or mg/L in the drinking water) as these are assumed to be already scaled according to the allometric principle, since ventilation rate and food intake directly depend on the basal metabolic rate. In this case the NOAEC is expressed as concentration (mg/m3), therefore a factor for allometric scaling is not needed.
AF for other interspecies differences:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: If no substance-specific data are available, the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (large r part). In case substance-specific information shows specific susceptibility differences between species, which are not related to differences in basal metabolic rate, the additional factor of 2.5 for ‘remaining differences’ should be modified accordingly. In this case the effects are not dependent on metabolic rate or systemic absorption and no further kinetic considerations apply. Therefore, the default factor for remaining uncertainties of 2.5 could be reduced to 1.
AF for intraspecies differences:
5
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: If the dose descriptor (e.g. N(L)OAEL, benchmark dose, etc.) has been derived from an animal study, animal intraspecies variation/differences has already to some extent been accounted for in that dose descriptor. Ideally therefore, the intraspecies factor should reflect the additional interspecies variability, i.e. the difference between variability in the human population and variability in the animal population. For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill.
AF for the quality of the whole database:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, is to be applied.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
20
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
AF for dose response relationship:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEC, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. In the ECHA’s Guidance a distinction is made between sub-chronic (usually refers to a 90 day study) and chronic studies (usually refers to a 1.5 - 2 year study). However the DNEL is derived from a 12-month study, which is not specifically stated in the ECHA guidance. Worst-case, a 12 month study could be considered “sub-chronic” and an assessment factor of 2 should be applied. However DNELs will be derived for workers and workers will not be exposed their entire life to DEEA, but rather a maximum of 40 years, which is half their life-expectancy. Therefore, an assessment factor of 1 is applied in this procedure.
AF for interspecies differences (allometric scaling):
4
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, allometric scaling extrapolates doses according to an overall assumption that equitoxic doses (when expressed in mg/kg bw/day) scale with body weight to the power of 0.250. This results in a default allometric scaling factor for the rat when compared with humans, namely 4.
AF for other interspecies differences:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: If no substance-specific data are available, the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (large r part). In case substance-specific information shows specific susceptibility differences between species, which are not related to differences in basal metabolic rate, the additional factor of 2.5 for ‘remaining differences’ should be modified accordingly. In this case the effects are not dependent on metabolic rate or systemic absorption and no further kinetic considerations apply. Therefore, the default factor for remaining uncertainties of 2.5 could be reduced to 1.
AF for intraspecies differences:
5
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: If the dose descriptor (e.g. N(L)OAEL, benchmark dose, etc.) has been derived from an animal study, animal intraspecies variation/differences has already to some extent been accounted for in that dose descriptor. Ideally therefore, the intraspecies factor should reflect the additional interspecies variability, i.e. the difference between variability in the human population and variability in the animal population. For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill.
AF for the quality of the whole database:
1
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.
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:
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:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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:
no hazard identified
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

Since diethylethanolamine is used at industrial and professional domains only, no exposure of the general population to diethylethanolamine is expected. Therefore no DNELs for the general population were calculated.