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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
1 170.8 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
Value:
23 300 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
11 708 mg/m³
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 ECHA guidance R7.5-7.7 (2017) for assessing long-term systemic toxicity. The selected conservative NOAEC has been derived from a 13-week inhalation toxicity study in rats (OECD TG 413): 23300 mg/m3. However, the exposure duration of the study was 6 hr/ day 5 days/ week which needs to be corrected to the default worker exposure of 8 hr/ day 5 days/ week. Additionally, a correction for activity driven differences in respiratory volumes in active workers in comparison to workers in rest (6.7 m3/ 10 m3) should be applied. This results in the following: 23300 * (6/8) * (6.7/10) = 11708 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-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor as the surrogate for the true no-adverse-effect-concentration (NAEC). 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 (OECD TG 413). Therefore, the default assessment factor of 1 is used.
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-response for human health, 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 NOAEC will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Since the dose descriptor is derived from an OECD TG 413 study, an additional assessment factor of 2 is applied to take into account the extrapolation of sub-chronic to chronic exposure data.
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-response for human health, as long as route-to-route extrapolation is not needed, allometric scaling should not be applied in cases where the dose unit (original or transformed) 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, a NOAEC was derived in terms of mg/m³, therefore additional assessment 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: Characterisation of dose-response for human health, interspecies differences result from variation in the sensitivity of species due to differences in toxicokinetics and toxicodynamics. Substance-specific information derived from PBPK modelling demonstrates that the blood/air partition coefficient in humans is approximately half of the blood/air partition coefficient in rats. In addition, the DNEL is being derived based on data from the most sensitive species (rat). Therefore, the additional factor for remaining differences is not needed.
AF for intraspecies differences:
5
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, intraspecies differences in human result from a multitude of biological factors such as genetic polymorphism affecting e.g. toxicokinetics/ metabolism, age, gender, health status and nutritional status. 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-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:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, there are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.
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:
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

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:
208.1 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):
20
Dose descriptor starting point:
NOAEC
Value:
23 300 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
4 161 mg/m³
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 ECHA guidance R7.5-7.7 (2017) for assessing long-term systemic toxicity. The selected conservative NOAEC has been derived from a 13-week inhalation toxicity study in rats (OECD TG 413): 23300 mg/m3. However, the exposure duration of the study was 6 hr/ day 5 days/ week which needs to be corrected to the default general population exposure of 24 hr/ day 7 days/ week. This results in the following: 23300 * (6/24) * (5/7) = 4161 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-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor as the surrogate for the true no-adverse-effect-concentration (NAEC). 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 (OECD TG 413). Therefore, the default assessment factor of 1 is used.
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-response for human health, 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 NOAEC will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Since the dose descriptor is derived from an OECD TG 413 study, an additional assessment factor of 2 is applied to take into account the extrapolation of sub-chronic to chronic exposure data.
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-response for human health, as long as route-to-route extrapolation is not needed, allometric scaling should not be applied in cases where the dose unit (original or transformed) 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, a NOAEC was derived in terms of mg/m³, therefore additional assessment 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: Characterisation of dose-response for human health, interspecies differences result from variation in the sensitivity of species due to differences in toxicokinetics and toxicodynamics. Substance-specific information derived from PBPK modelling demonstrates that the blood/air partition coefficient in humans is approximately half of the blood/air partition coefficient in rats. In addition, the DNEL is being derived based on data from the most sensitive species (rat). Therefore, the additional factor for remaining differences is not needed.
AF for intraspecies differences:
10
Justification:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, intraspecies differences in human result from a multitude of biological factors such as genetic polymorphism affecting e.g. toxicokinetics/ metabolism, age, gender, health status and nutritional status. For the general population, as standard procedure for threshold effects a default assessment factor of 10 is to be used, which is sufficient to protect the larger part of the population, including e.g. children and the elderly.
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-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:
In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose-response for human health, there are no remaining uncertainties. Since there are no further uncertainties, the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.
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:
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

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