Registration Dossier
Registration Dossier
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EC number: 605-143-8 | CAS number: 158318-67-3
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 23.5 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):
- 75
- Dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 1 760 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Modification of relevant dose descriptor: NOAEL (oral, rat) -> NOAEC (inhalation, general pop 24h) is necessary as there is no adequate study available covering this endpoint and for workers the inhalation NOAEC needs to be corrected caused by different breathing rates.
In conclusion: NOAEC (inhalation, worker 8h) is calculated following ECHA Guidance, 100% absorption is assumed.
- 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 NOAEL, 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:
- 6
- Justification:
- Extrapolation from subacute to chronic exposure.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Already considered in route-to-route correction
- AF for other interspecies differences:
- 2.5
- Justification:
- Default value according to ECHA guidance
- AF for intraspecies differences:
- 5
- Justification:
- Default value according to ECHA guidance
- AF for the quality of the whole database:
- 1
- Justification:
- The database is of good quality.
- AF for remaining uncertainties:
- 1
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:
- 33.4 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):
- 300
- Dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 10 000 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
As a conservative value, the NOAEL of 1000 mg/kg bw based on maternal toxicity in an oral developmental toxicity study with a 14 day (sub-acute) exposure is used as starting point for hazard assessment (BASF 2016).
The DNEL for dermal route cannot be derived directly from an oral study. Modification of the relevant dose descriptor is necessary.
NOAEL (oral, rat)àNOAEL (dermal, rat)
It is known for cosmetic ingredients having a MW above 300 g/mol and log pow >5 that a dermal absorption of approximately 10% can be expected ((Kroes et al., Food Chem Toxicol 2007 Dec; 45(12): 2533-62). Even if the substance is not a cosmetic the phys chem data suggest a low dermal absorption.
With a molecular weight of at least 312 Da and a log Kow of > 6.5, the substance is unlikely to be absorbed dermally.
As worst case, a dermal absorption of 10% is assumed and used for starting point correction.
- 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 NOAEL, 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:
- 6
- 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-acute toxicity study is available, default assessment factor of 6 is to be applied, as a standard 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 0.75. This results in a default allometric scaling factor for the rat when compared with humans, namely 4. In ECETOC Derivation of Assessment Factors for Human Health Risk Assessment – Technical Report No. 86 and ECETOC Guidance on Assessment Factors to Derive a DNEL – Technical Report No. 110, a similar approach is followed. Toxicokinetic differences can be explained by basal metabolic rate which can be accounted for by allometric scaling. The underlying principle is that due to the faster metabolic rate of smaller animals, humans would less effectively detoxify and/or excrete xenobiotics than laboratory animals and thus are more vulnerable. The allometric scaling factor for the rat versus humans is 4.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default assessment factor according to ECHA guidance.
- AF for intraspecies differences:
- 5
- Justification:
- Default assessment factor according to ECHA guidance.
- AF for the quality of the whole database:
- 1
- Justification:
- In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterization 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:
- 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 remaining uncertainties should be used where necessary. As 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)
- Most sensitive endpoint:
- sensitisation (skin)
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
References (not included as endpoint study record)
- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health.Version 2.1. ECHA-2012.
- ECETOC (2010). Technical Report 110.Guidance on assessment factors to derive a DNEL.
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:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
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
DNEL related information
- Explanation for the modification of the dose descriptor starting point:
No consumer uses were identified. The general population does not get in contact with the substance. Therefore, in accordance with the REACH legislation (regulation (EC) No 1907/2006, Annex I, 1.4.1), no DNEL has to be derived for the general population.
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.
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