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:
1.5 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:
1.5 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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
AF for intraspecies differences:
5

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;

Environment: Due to the identified uses, exposure to the environment can be excluded.

Human health: As a basis for exposure-based waiving, the TTC concept as devised by Munro et al. [1, 2] is applied. MBTester is predicted to fall within Cramer Class III (high hazard). Within Cramer class III, 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 MBTester (Class III) is 0.15 mg/kg bw/day corresponding to a very low DNEL of 1.5 µg/kg bw/d.

 

(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 of MBTester to humans or the environment can be considered as negligible and therefore below the derived DNEL or PNEC. Please refer to chapter 9 and 10 of the CSR.

 

Finally, 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 MBTester 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, only the dermal route of exposure is of relevance in the context of risk assessment.

 

Chronic Effects

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

MBTester is chemically well described and without indication of possible genotoxic effects. Therefore, the substance can be linked to the Cramer Class III (high hazard) as described in Munro et al., 1999. For Cramer Class III a human exposure threshold of 1.5 μg/kg bw/d (corresponding to 1.5μg/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 1.5 µg/kg bw/day.

 

Acute Effects

The substance MBTester does not cause toxic effects in the conducted acute or sensitizing toxicity studies.

 

References

 

[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 MBTester is not used by consumers. Likewise, consumers are not exposed

directly to MBTester via products or articles.