Registration Dossier

Administrative data

Workers - 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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
30 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: TTC concept
Overall assessment factor (AF):
1
Modified dose descriptor starting point:
other: TTC
Value:
30 µg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
It is assumed that oral and dermal absorption rates are equal.
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
AF for intraspecies differences:
1
AF for the quality of the whole database:
1
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:
DNEL (Derived No Effect Level)
Value:
2.5 mg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
other: NOEL 12.5 mg/cm²
AF for intraspecies differences:
5
Justification:
workers
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

According to the REACH Regulation, Annex XI.3 Substance-tailored exposure-driven testing. 3.1 Testing in accordance with Sections 8.6 and 8.7 of Annex VIII and in accordance with Annex IX and Annex X may be omitted, based on the exposure scenario(s) developed in the Chemical Safety Report.

3.2. (a) The manufacturer or importer demonstrates and documents that all of the following conditions are fulfilled:

(i) the results of the exposure assessment covering all relevant exposures throughout the life cycle of the substance demonstrate the absence of or no significant exposure in all scenarios of the manufacture and all identified uses as referred to in Annex VI Section 3.5.

The results of the exposure assessment are described in the CSR chapter 9 and 10. No significant exposure in all scenarios of the manufacture and all identified uses were identified.

(ii), a DNEL or a PNEC can be derived from results of available test data for the substance concerned taking full account of the increased uncertainty resulting from the omission of the information requirement, and that DNEL or PNEC is relevant and appropriate both to the information requirement to be omitted and for risk assessment purposes; (iii) the comparison of the derived DNEL or PNEC with the results of the exposure assessment shows that exposures are always well below the derived DNEL or PNEC.

Due to the identified uses exposure to the environment can be excluded. Exposure

As a basis for exposure-based waiving, the TTC concept as devised by Munro et al. [1,2] is applied. Di-2 -EHTDG is predicted to fall within Cramer Class I (low hazard). Within Cramer class I, the 5th-percentile NOEL has been identified from chronic oral studies or other oral studies e.g., developmental toxicity, if they were more sensitive. The majority of NOELs were defined by studies in the rat.

The generic oral NOEL applicable to Di-2 -EHTDG (Class I) is 3.0 mg/kg bw/day corresponding to a very low DNEL of 30 µg/kg bw/d.

 

[1] Munro, IC,Ford, RA, Kennepohl, E, Sprenger, JG (1996).Correlation of Structural Classwith No-Observed-Effect Levels: A Proposal for Establishing a Threshold of Concern. Food Chem. Toxicol. 34 829-867.

[2] Munro, IC, Kennepohl, E, Kroes, R (1999). A procedure for the safety evaluation of flavouring substances. Food and Chemical Toxicology 37, 207-232.

 

(iii) the comparison of the derived DNEL or PNEC with the results of the exposure assessment shows that exposure are always well below the derived DNEL or PNEC.

The exposure are well below the derived DNEL or PNEC. Please refer to chapter 9 and 10 of the CSR.

Therefore, the EU REACH Regulation clearly indicates the need for non-animal methods and provides the opportunity of waiving testing based on exposure considerations. The use of the TTC approach within REACH can be an appropriate tool in this context.With regard to human exposure, the TTC approach is only applicable in cases with detailed information on all anticipated uses and use scenarios.

In the case of the rubber additive Di-2-EHTDG all information on uses and use scenarios are collected and direct exposure of the substance to humans could only be identified for industrial workers. For industrial exposure scenarios, inhalation and dermal route of exposure should be considered, whereas the oral route can be excluded.

 

Chronic Effects

As a basis for exposure-based waiving, the TTC concept as developed by Munro et al. [1, 2] is applied:

Di-2-EHTDG is chemically well described and without indication of possible genotoxic effects. Therefore, the substance can be linked to the Cramer Class I (low hazard) as described in Munro et al., 1999. For Cramer Class I a human exposure threshold of 30 μg/kg bw/d (corresponding to 1800 μg/person/d) was proposed, using the 5th percentile value of distribution of NOELs for each class of chemicals, a body weight of 60 kg, and an assessment factor of 100 [1].

 

The oral DNEL for workers can therefore be directly derived without applying any assessment factors, because as mentioned above the assessment factors for intra- and interspecies variations are already implemented in the TTC concept of Munro. Thus the oral DNEL corresponds to the TTC value of 30 µg/kg bw/day.

 

Acute Effects

The present TTC concept cannot be applied for establishing tolerable thresholds for the toxicological endpoint of sensitization. In the case of Di-2-EHTDG the most sensitive acute effect is skin sensitization. An EC3 of about 50% was found. According to the ECHA Guidance Document R.8 an EC3 in % can be converted into a local dermal NOEL with the following equation:

EC3 [%]*250 [μg/cm²/% ] = NOEL [μg/cm²]

For Di-2 -EHTDG, the dermal NOEL is 50% * 250 µg/cm²/% = 12.5 mg/cm². Applying an intraspecies factor of 5, the local dermal DNEL is 2.5 mg/cm².

 

[1]Munro, IC, Ford, RA, Kennepohl, E, Sprenger, JG (1996).Correlation of structural class with no-observed-effect levels: a proposal for establishing a threshold of concern. Food and Chemical Toxicology 34, 829-867.

 

[2] Munro, IC, Kennepohl, E, Kroes, R (1999). A procedure for the safety evaluation of flavouring substances. Food and Chemical Toxicology 37, 207-232.

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

DNELs for the general population have not been proposed because Di-2-EHTDG is not used by consumers. Likewise, a direct and relevant exposure of consumers to Di-2 -EHTDG via products or articles is not expected.