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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.69 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:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
352 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 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:
6.67 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:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As a conservative value, the NOAEL of 200 mg/kg bw based on maternal toxicity in an oral developmental toxicity study with a 14 day (sub-acute) exposure to a close analogue 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) --> NOAEL (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 ranging from 356 and 4747 Da and a log Kow higher than 4, 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:
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

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:
hazard unknown (no further information necessary)
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