Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
176 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):
3
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
529 mg/m³
Explanation for the modification of the dose descriptor starting point:

The substance does not need to be classified and labelled for systemic toxicity, but adverse effects were seen in the repeated dose toxicity studies. In absence of inhalation toxicity data, the NOAEL from the sub-acute (Zenolide) and (sub)chronic Ethylene glycol oral repeated-dose toxicity study including information on reproduction/developmental toxicity information is used for derivation of the DNEL-long-term for the inhalation route.

Route-to route extrapolation can be done because there is adequate oral toxicity data; the critical effect is systemic rather than the site of contact. Also, there is no evidence that the compound is subject to ‘first pass’ metabolism which would lead to higher inhalation toxicity compared to oral toxicity.

Based on Ethylene glycol effects (a metabolite of Zenolide), it can be concluded that the oral absorption is 100% and therefore the inhalation route absorption is the same as oral absorption (see Toxico-kinetic section).

The respiratory volume of rats (0.38 m3/kg bw) is multiplied by the respiratory volume of human (6.7 m3/person) and corrected for the respiratory volume for light activity to address the workers (10 m3/person). Therefore, the modified dose descriptor is calculated as follows: 300 / 0.38 x (6.7/10) = 529 mg/m3

AF for dose response relationship:
1
Justification:
No additional assessment factor for dose response is needed because the dosing was well spaced in the studies and an overall NOAEL was derived from these repeated dose toxicity studies with Zenolide and Ethylene glycol (ECHA’s guidance, R.8.4.3.1, November, 2012).
AF for differences in duration of exposure:
1
Justification:
An assessment factor of 1 has been applied to extrapolate the NOAEL from sub-chronic to a chronic study which deviates from R.8.4.3.1 and table R.8-5 (ECHA’s guidance, November, 2012). This deviation is justified because the NOAEL of Ethylene glycol is applicable for chronic exposure as presented in the Endpoint summary for repeated dose toxicity and based on Corley et al., 2008.
AF for interspecies differences (allometric scaling):
1
Justification:
An assessment factor of 1 has been used because the difference in metabolic rate between rat and humans has been accounted for in the conversion of NOAEL in mg/kg bw to the NOAEC mg/m3, as presented in ECHA’s guidance R.8, figure R. 8-2 (November, 2012). It should be noted that this is conservative because it has been shown by Corley et al. (2008) that humans are less sensitive compared to rats based on clearance (Table 8 in Corley et al., 2008).
AF for other interspecies differences:
1
Justification:
Additional assessment factors for interspecies differences are not needed as has been derived in the ECETOC report (TR 110, 2010) based on a review of the scientific literature. The concept of adjusting animal dose by allometric scaling predicts reasonably well the appropriate dose in humans. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. This analysis is based on a comparison of animal to actual human data that per se includes intraspecies variability in humans (see below at intraspecies differences). In addition to this, Wistar rats being more sensitive for Ethylene glycol effects compared to other rat species, mice and humans further supports the AF of 1 for interspecies differences.
AF for intraspecies differences:
3
Justification:
An assessment factor of 3 has been used to account for the intraspecies differences. This factor has been retrieved by ECETOC (TR110, 2010). The ECETOC analysis has been based on a comparison between animal and actual human data that per se includes intraspecies variability in humans. In addition, the human population under investigation comprised cancer patients; this represents a very sensitive subpopulation. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. Thus, this standard deviation represented by the GSD of 2.5-2.6 is probably due to potential differences in biological sensitivity between species and includes intraspecies differences.
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:
An assessment factor of 1 is applicable, because there are no remaining uncertainties, which have not already been accounted for.
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 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):
6
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The substance fulfils the REACH Annex VII to Annex XI information requirements in accordance with R7.5-7.7 (2017) for assessing long-term systemic toxicity. In absence of dermal toxicity data, the NOAEL from the sub-acute (Zenolide) and (sub)chronic Ethylene glycol oral repeated-dose including information on reproduction/developmental toxicity information is used for derivation of the DNEL-long-term for the dermal route.

Route-to route extrapolation can be done because there is adequate oral toxicity data; the critical effect is systemic rather than the site of contact. Also, there is no evidence that the compound is subject to ‘first pass’ metabolism which would lead to higher dermal toxicity compared to oral toxicity. Based on Ethylene glycol effects (a metabolite of Zenolide) it can be concluded that the oral absorption is 100%. Though the dermal route exposure is generally slower and lower compared to the oral route the absorption to the dermal route is also considered 100% not to underestimate the dermal exposure route (see Toxico-kinetics section and IGHRC, 2006 as mentioned in the ECHA guidance, R.8.4.2, November, 2012).

AF for dose response relationship:
1
Justification:
No additional assessment factor for dose response is needed because the dosing was well spaced in the studies used for Zenolide and Ethylene glycol (ECHA’s guidance, R.8.4.3.1, November, 2012).
AF for differences in duration of exposure:
1
Justification:
An assessment factor of 1 has been applied to extrapolate the NOAELs from sub-chronic to a chronic study which deviates from R.8.4.3.1 and table R.8-5 (ECHA’s guidance, November, 2012). This deviation is justified because the NOAEL of Ethylene glycol is applicable for chronic exposure as presented in the Endpoint summary for repeated dose toxicity.
AF for interspecies differences (allometric scaling):
2
Justification:
For allometric scaling usually a factor of 4 is applicable using ECHA guidance. This allometric scaling in the present case is not needed. This is because the NOAEL was based on Oxalic acid nephropathy in the Wistar rat that could be related to Ethylene glycol formation. Wistar rats are more sensitive for the Ethylene glycol Oxalic acid nephropathy compared to other rat species, mice and humans as explained in the Repeated dose Endpoint summary.
AF for other interspecies differences:
1
Justification:
Additional assessment factors for interspecies differences are not needed as has been derived in the ECETOC report (TR 110, 2010) based on a review of the scientific literature. The concept of adjusting animal dose by allometric scaling predicts reasonably well the appropriate dose in humans. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. This analysis is based on a comparison of animal to actual human data that per se includes intraspecies variability in humans (see below at intraspecies differences).
AF for intraspecies differences:
3
Justification:
An assessment factor of 3 has been used to account for the intraspecies differences. This factor has been retrieved by ECETOC (TR110, 2010). The ECETOC analysis has been based on a comparison between animal and actual human data that per se includes intraspecies variability in humans. In addition, the human population under investigation comprised cancer patients, these represent a very sensitive subpopulation. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. Thus, this standard deviation represented by the GSD of 2.5-2.6 is probably due to potential differences in biological sensitivity between species and includes intraspecies differences.
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:
An assessment factor of 1 is applicable, because there are no remaining uncertainties, which have not already been accounted for.
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

In deriving the DNELs for hazard identification for inhalation and the dermal route of exposure ECHA’s guidance is used where relevant, which is generally conservative by using default values in absence of data outside the requirements of REACH regulation Annex VII to Annex XI. Based on specific data for the substance and its metabolite Ethylene glycol the AFs for systemic toxicity have been adapted and justified.

In addition, the assessment factors used have been adequately documented. For inter- and intraspecies differences, assessment factors have been used which were conducted to be scientifically sound by ECETOC (TR 110, 2010) and which are based on a thorough review of the scientific literature. Therefore, the DNELs for all human health endpoints relevant for workers are considered sufficiently conservative to be used for the risk characterization.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
52 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:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
260 mg/m³
Explanation for the modification of the dose descriptor starting point:

The substance does not need to be classified and labelled for systemic toxicity, but adverse effects were seen in the repeated dose toxicity study. In absence of inhalation toxicity data, the NOAEL from the sub-acute (Zenolide) and (sub)-chronic Ethylene glycol oral repeated-dose toxicity study including information on reproduction/developmental toxicity information is used for derivation of the DNEL-long-term for the inhalation route. Route-to route extrapolation can be done because there is adequate oral toxicity data; the critical effect is systemic rather than the site of contact. Also, there is no evidence that the compound is subject to ‘first pass’ metabolism which would lead to higher inhalation toxicity compared to oral toxicity. Based on Ethylene glycol effects (a metabolite of Zenolide) it can be concluded that the oral absorption is 100% and therefore the inhalation route absorption is the same as oral absorption (see Toxico-kinetic section).  Starting point is the NOAEL of 300 mg/kg bw. The inhalation and oral absorption are both considered to be 100% (See Toxico-kinetic assessment) and therefore a factor 2 for route to route extrapolation is not needed. For the oral rat repeated dose to human inhalation toxicity extrapolation the following formula is used: 300 mg/kg bw /1.15=260 mg/m3 as is standard according to ECHA guidance.

AF for dose response relationship:
1
Justification:
No additional assessment factor for dose response is needed because the dosing was well spaced in the studies used for Zenolide and Ethylene glycol (ECHA’s guidance, R.8.4.3.1, November, 2012).
AF for differences in duration of exposure:
1
Justification:
An assessment factor of 1 has been applied to extrapolate the NOAEL from sub-chronic to a chronic study which deviates from R.8.4.3.1 and table R.8-5 (ECHA’s guidance, November, 2012), This deviation is justified because the NOAEL of Ethylene glycol is applicable Zenolide and for chronic exposure as presented in the repeated dose toxicity Endpoint summary.
AF for interspecies differences (allometric scaling):
1
Justification:
An assessment factor of 1 has been used because the difference in metabolic rate between rat and humans has been accounted for in the conversion of NOAEL in mg/kg bw to the NOAEC mg/m3, as presented in ECHA’s guidance R.8, figure R. 8-2 (November, 2012).
AF for other interspecies differences:
1
Justification:
Additional assessment factors for interspecies differences are not needed as has been derived in the ECETOC report (TR 110, 2010) based on a review of the scientific literature. The concept of adjusting animal dose by allometric scaling predicts reasonably well the appropriate dose in humans. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. This analysis is based on a comparison of animal to actual human data that per se includes intraspecies variability in humans (see below at intraspecies differences).
AF for intraspecies differences:
5
Justification:
An assessment factor of 5 has been used to account for the intraspecies differences. This factor has been retrieved by ECETOC (TR110, 2010). The ECETOC analysis has been based on a comparison between animal and actual human data that per se includes intraspecies variability in humans. In addition, the human population under investigation comprised cancer patients, this represents a very sensitive subpopulation. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. Thus, this standard deviation represented by the GSD of 2.5-2.6 is probably due to potential differences in biological sensitivity between species and includes intraspecies differences. To keep an additional factor for the sensitivity of the general population compared to workers, the AF used is 5 instead of 3.
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:
An assessment factor of 1 is applicable, because there are no remaining uncertainties, which have not already been accounted for.
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:
30 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):
10
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The substance fulfils the REACH Annex VII to Annex XI information requirements in accordance with R7.5-7.7 (2016) for assessing long-term systemic toxicity.

In absence of dermal toxicity data, the NOAEL from the sub-acute (Zenolide) and (sub)-chronic Ethylene glycol oral repeated-dose including information on reproduction/developmental toxicity information is used for derivation of the DNEL-long-term for the dermal route.

Route-to route extrapolation can be done because there is adequate oral toxicity data; the critical effect is systemic rather than the site of contact. Also, there is no evidence that the compound is subject to ‘first pass’ metabolism which would lead to higher dermal toxicity compared to oral toxicity.

Based on Ethylene glycol effects (a metabolite of Zenolide) it can be concluded that the oral absorption is 100%. Though the dermal route exposure is generally slower and lower compared to the oral route the absorption to the dermal route is also considered 100%. This 100% is used not to underestimate the effects of the dermal exposure route (see Toxico-kinetics section and IGHRC, 2006 as mentioned in the ECHA guidance, R.8.4.2, November, 2012).

AF for dose response relationship:
1
Justification:
No additional assessment factor for dose response is needed because the dosing was well spaced in the studies used for Zenolide and Ethylene glycol (ECHA’s guidance, R.8.4.3.1, November, 2012).
AF for differences in duration of exposure:
1
Justification:
An assessment factor of 1 has been applied to extrapolate the NOAEL from sub-chronic to a chronic study deviates from R.8.4.3.1 and table R.8-5 (ECHA’s guidance, November, 2012), This deviation is justified because the NOAEL of Ethylene glycol is applicable for chronic exposure as presented in the Repeated dose Endpoint summary.
AF for interspecies differences (allometric scaling):
2
Justification:
For allometric scaling usually a factor of 4 is applicable using ECHA guidance. This allometric scaling in the present case is not needed. This is because the NOAEL was based on Oxalic acid nephropathy in the Wistar rat that could be related to Ethylene glycol formation. Wistar rats are more sensitive for the Ethylene glycol Oxalic acid nephropathy compared to other rat species, mice and humans as explained in the Repeated Dose Endpoint summary.
AF for other interspecies differences:
1
Justification:
Additional assessment factors for interspecies differences are not needed as has been derived in the ECETOC report (TR 110, 2010) based on a review of the scientific literature. The concept of adjusting animal dose by allometric scaling predicts reasonably well the appropriate dose in humans. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. This analysis is based on a comparison of animal to actual human data that per se includes intraspecies variability in humans (see below at intraspecies differences).
AF for intraspecies differences:
5
Justification:
An assessment factor of 5 has been used to account for the intraspecies differences. This factor has been retrieved by ECETOC (TR110, 2010). The ECETOC analysis has been based on a comparison between animal and actual human data that per se includes intraspecies variability in humans. In addition, the human population under investigation comprised cancer patients, this represents a very sensitive subpopulation. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. Thus, this standard deviation represented by the GSD of 2.5-2.6 is probably due to potential differences in biological sensitivity between species and includes intraspecies differences. To keep an additional factor for the sensitivity of the general population compared to workers, the AF used is 5 instead of 3.
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:
An assessment factor of 1 is applicable, because there are no remaining uncertainties, which have not already been accounted for.
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:
30 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):
10
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The substance fulfils the REACH Annex VII to Annex XI information requirements in accordance with R7.5-7.7 (2016) for assessing long-term systemic toxicity.

Route to route exposure is not needed. Oral repeated dose toxicity studies are available and therefore the oral rat NOAEL can be used for DNEL derivation. The NOAEL from the sub-acute (Zenolide) and sub-chronic Ethylene glycol oral repeated-dose including information on reproduction/developmental toxicity information is used for derivation of the DNEL-long-term for the oral route.

Based on Ethylene glycol effects (a metabolite of Zenolide) it can be concluded that the oral absorption is 100% as is explained in the Toxico-kinetic section.

AF for dose response relationship:
1
Justification:
No additional assessment factor for dose response is needed because the dosing was well spaced in the studies used for Zenolide and Ethylene glycol (ECHA’s guidance, R.8.4.3.1, November, 2012).
AF for differences in duration of exposure:
1
Justification:
An assessment factor of 1 has been applied to extrapolate the NOAEL from sub-chronic to a chronic study which deviates from R.8.4.3.1 and table R.8-5 (ECHA’s guidance, November, 2012), This deviation is justified because the NOAEL of Ethylene glycol is applicable for chronic exposure as presented in the Repeated dose Endpoint summary.
AF for interspecies differences (allometric scaling):
2
Justification:
For allometric scaling usually a factor of 4 is applicable using ECHA guidance. This allometric scaling in the present case is not needed. This is because the NOAEL was based on Oxalic acid nephropathy in the Wistar rat that could be related to Ethylene glycol formation. Wistar rats are more sensitive for the Ethylene glycol Oxalic acid nephropathy compared to other rat species, mice and humans as explained in the Repeated Dose Endpoint summary.
AF for other interspecies differences:
1
Justification:
Additional assessment factors for interspecies differences are not needed as has been derived in the ECETOC report (TR 110, 2010) based on a review of the scientific literature. The concept of adjusting animal dose by allometric scaling predicts reasonably well the appropriate dose in humans. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. This analysis is based on a comparison of animal to actual human data that per se includes intraspecies variability in humans (see below at intraspecies differences).
AF for intraspecies differences:
5
Justification:
An assessment factor of 3 has been used to account for the intraspecies differences. This factor has been retrieved by ECETOC (TR110, 2010). The ECETOC analysis has been based on a comparison between animal and actual human data that per se includes intraspecies variability in humans. In addition, the human population under investigation comprised cancer patients. This represents a very sensitive subpopulation. A Geometric Standard Deviation (GSD) of 2.5-2.6 suggests the likelihood of some variability or additional uncertainty around the predicted NOAEL in humans. Thus, this standard deviation represented by the GSD of 2.5-2.6 is probably due to potential differences in biological sensitivity between species and includes intraspecies differences. To take into account the sensitivity of general population compared to the workers, the AF used is 5 instead of 3.
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:
An assessment factor of 1 is applicable, because there are no remaining uncertainties, which have not already been accounted for.
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

In deriving the DNELs for hazard identification for inhalation and the dermal route of exposure ECHA’s guidance is used, where applicable, which is generally conservative by using default values in absence of data outside the requirements of REACH regulation Annex VII to Annex XI. Based on specific data for the substance and its metabolite Ethylene glycol the AFs for systemic toxicity have been adapted and justified. In addition, the assessment factors used have been adequately documented. For inter- and intraspecies differences, assessment factors have been used which were conducted to be scientifically sound by ECETOC (TR 110, 2010) and which are based on a thorough review of the scientific literature. Therefore, the DNELs for all human health endpoints relevant for the general population are considered sufficiently conservative to be used for the risk characterization.