Assessment of the Equivalence of Technical Materials - European ...

More documents

Recommendations

Info

New impurities of unknown toxicological concern (>1g/kg) or increased levels of significantbut non-relevant impurities: these impurities would elicit a further evaluationAssuming suitable information is available, the competent authority considers whether thehazard of the new material is significantly increased compared with that of the referencesource by the presence of the impurity at the respective level 6 .If not enough information is submitted, further data should be generated as indicated inAppendix IV.If worker/operator and consumer exposure to the impurity is below the threshold of concern(TTC, Kroes et al., 2004 & 2005), it may be acceptable to waive the need to generate newdata, but the applicant has to submit a reasoned case 7 . Basically it is a management decision,as to whether the TTC concept is sufficiently conservative to protect the population and toallow decision-making and whether the uncertainties due to the assumptions in this exposureestimation are acceptable.The choice of an appropriate TTC value is a case-by-case decision, which takes into accountinter alia the known/assumed properties of the impurity. Currently, further advice is neededto support the choice and harmonise the approaches between the MSs. The available openliterature on the TTC concept as well as a recently submitted report by CRD could be visitedto support such considerations (Applicability of thresholds of toxicological concern in thedietary risk assessment of metabolites, degradation and reaction products of pesticides;scientific / technical report submitted to EFSA prepared by Chemicals Regulation Directorate(CRD), UK, final report Sept. 2009).b) Determination of an acceptable upper limit concentration for an impurity oftoxicological concernIf an impurity of toxicological concern in the new source does not exceed an acceptable upperlimit concentration, it may help to indicate that there is no increased hazard in the new sourcecompared with the reference source.Initially the following are examined:- Consider case presented by the applicant- Was the impurity present in the test material used in critical toxicity studies and didthe findings indicate that at this concentration the impurity was not having an effect ofconcern?6 It is conceivable that the hazard of the new source is significantly increased by the sum of all new or increasedimpurities rather than by one impurity alone. In this case which is expected to occur only very seldomly,equivalence would also have to be denied.7 The maximum possible level of human exposure to the impurity can be calculated assuming that the impuritywill be present at the maximum level specified in technical grade a.s, exposure to the a.s. will be at 100 % of thea.s. reference doses (AOEL, ADI, ARfD), and that the exposed person has a bw of 70 kg.The following calculation can be applied:Exposure [µg/person/d] = RfD for a.s. [mg/kg bw/d] * 70 kg bw * specified maximum amount of impurity in thea.s. [g/kg=µg/mg].This approach makes some assumptions that may not always be met: e. g. (1) as the AOEL is a systemic value, itis presumed that dermal, oral and inhalation absorption is comparable to the a.s.; (2) the behaviour as a residue iscomparable to the a.s.8
If the answer is yes, it might be appropriate to use the level of the impurity in the testedmaterial as the acceptable upper limit concentration but expert judgement will be particularlyimportant.If the answer is no, consider the guidance in Appendix IV and V.Note: the limit for a relevant impurity may be set at a level less than 1 g/kg (
Page 1 and 2: EUROPEAN COMMISSIONHEALTH AND CONSU
Page 3 and 4: 1 Implementing scheduleThis amended
Page 5 and 6: Significant impuritiesImpurities th
Page 7: 7.1.2 Evaluation processThe objecti
Page 11 and 12: a) Prediction of the expected incre
Page 13 and 14: Bridging across different media (e.
Page 15 and 16: Loewe, S, Muischnek, H. (1926). Üb
Page 17 and 18: 1. Ascertainment of the necessity t
Page 19 and 20: Appendix Ib: Evaluation and decisio
Page 21 and 22: Appendix III, which is based on a l
Page 23 and 24: tests with information provided on
Page 25 and 26: Appendix IV Guideline triggers for
Page 27 and 28: Appendix V How to judge what is an
Page 29 and 30: Appendix VI Example calculations fo
Page 31 and 32: TABLE OF CONTENTS1 STATEMENT OF THE
Page 33 and 34: A.4 MANUFACTURER’S DEVELOPMENT CO
Page 35 and 36: XXXXXXAccuracy:XXXXXXPrecisionXXXXX
Page 37: SUMMARY OF THE TECHNICAL EQUIVALENC

Assessment of the Equivalence of Technical Materials - European ...

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?