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White Paper on the Future Chemical Policy inthe European Union - Implications for AnimalWelfareUrsula G. SauerAkademie fur Tierschutz, D-Neubiberg

SummaryIn February 2001, the European Commission adopted a WhitePaper on a Future Chemicals Policy. Its main goals are betterto protect humans and the environment from unknown risksthrough chemicals. The "promotion of non-animal testing" isone of the key elements of the proposed strategy. For lowproduction volume chemicals, only data from in vitro tests areto be requested. The data requirements for higher productionvolume chemicals shall be designed flexibly so that only datarelevant for the respective chemical are collected. From thepoint of view of animal welfare concrete risk managementstrategies should he defined before test batteries are puttogether. The test catalogues currently listed in the Classifica-tion Directive 6715481EECare to be replaced by tiered testingstrategies, and concrete waiving strategies are to be designed sothat the requested tailor-made testing can actually be realized.Another essential prerequisite for the promotion of non-animaltesting is that the funding of alternative method research isformulated as a key action with a concrete budget in the SixthResearch Framework Program of the European Union.

Zusammenfassung: Das WeiBbuch fur eine zukunftige EU-Chemikalienpolitik - Tierschutzrelevante AspekteIm Februar 2001 hat die Europiiische Kommission einWeijJbuchfur eine zukiinftige Chemikalienpolitik vorgelegt.

1 Background

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The great majority of chemicals currentlyin use are so-called existing chemicals thatwere put on the market before 1981, whenthere was no legislation in force regulat-ing the marketing or use of chemicals.100.106 chemicals are listed in the Euro-pean Inventory of Existing CommercialChemical Substances (EINECS) and areregulated by Council Regulation (EEC)793/93 on the evaluation and control ofrisks of existing substances (OJ L 84,5.4.1993, p.l). It is recognised that for thevast majority of the existing chemicals theeffects on humans or the environment are

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Ziel ist es, den Menschen und die Umwelt besser als bisher vorunbekannten Gefahren durch Chemikalien zu schiazen. ImWeijJbuehwird .Forderung von Priifungen ohne versuchstie-re" als eines del' Schliisselelemente der neuen Chemikalienpo-litik genannt. Um dies zu verwirklichen, sollen fiir niedrigvolu-mige Steffe nur Daten aus in vitro Verfahren vorgeschriebenwerden. Die Datenanforderungen jur hohervolumige Stoifesollen flexibel gestaltet werden, so dass nur die fur dieBewertung des jeweiligen Stoffes notwendigen Tests durchge-fiihrt werden. Aus der Sicht des Tierschutzes ist weiterhin zufordern, dass konkrete Risikomanagementstrategien festgelegtwerden, bevor Testbatterien ausgestaltet werden. Die Testbat-terien, die derzeit in der Klassifizierungsrichtlinie 6715481EECaufgefuhrt werden, sind durcli stufenweise hierarchisierteTestreihen zu ersetzen. Die Forderung nacn zugeschnittenenTestbatterien muss so ausgestaltet werden, dass sie in derPraxis greifen kann. Wesentlich ist auch, dass die im WeijJbuehformulierte Forderung der verstarkten Forderung tierver-suchsfreier Verfahren im 6. Forschungsrahmenprogramm derEU konkret umgesetzt wird.

Keywords: chemicals, legislation, safety testing, risk manage-ment, in vitro toxicity, test strategies

unknown (Danish Board of Technology,1996).In contrast, only approximately 2.400

chemicals have been put on the marketafter 1981 and are thus listed as newchemicals in the European List of Noti-fied Chemical Substances (ELINCS). Themajor legal instruments currently in forcein the European Union in regard to themarketing and use of new chemical sub-stances and preparations are Council Di-rective 67/548/EEC relating to the classi-fication, packaging and labeling of dan-gerous substances, as amended (OJ 196,16.8.1967, p. 1), Directive 88/379/EECrelating to the classification, packaging

and labeling of dangerous preparations(OJL 187, 16.7.1988,p.14)andDirec-tive 76/769/EEC relating to restrictionson the marketing and use of certain dan-gerous substances and preparations (OJL 262, 27.9.1976, p. 20]).On November 18'h,1998, the Commis-

sion adopted a report on the evaluation ofthe EU legislation on industrial chemicals(Commission of the European Commu-nities, 1998). It was acknowledged thatthere was a general lack of knowledgeabout the properties and the uses of exist-ing substances. The risk assessment pro-cess was recognised to be slow and re-source-intensive and not to allow the sys-

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tern to work efficiently and effectively. Inconsequence, in June 1999, the Councilof Environmental Ministers assigned theGeneral Directorates Environment andEnterprise (DO ENV and ENTR) of theEuropean Commission with the joint taskto submit a policy document outlining anew chemicals strategy by the end of theyear 2000. After a small delay, this WhitePaper for a future Chemicals Policy wasadopted on February 13th, 2001 (Com-mission of the European Communities,2001a).

2 Future EU chemicals policy -political developments relevant foranimal welfare

In the White Paper, seven key elements ofthe strategy for a new Chemicals Policyare defined, such as the protection of hu-man health and the environment and dif-ferent economical factors. Number six ofthe seven key elements is the "promotionof non-animal testing". This key elementis subdivided into three objectives:

"Maximising use of non-animal testmethods: Testing requirements will be metasfar as practicable through use of exist-ing non-animal test methods.Encouraging development of new non-

animal test methods: Development of newnon-animal test methods will be encour-aged.Minimising test programs: Measures to

increase testing thresholds and moreflex-ible test regimes will limit the needfor test-ing."

Chapter 3.2. of the White Paper furtherspecifies how laboratory animals are to beprotected in a revised chemicals policy:"The following elements of the new sys-tem have been developed with a view tokeep animal testing to a minimum:~ Existing information on the toxicity andecotoxicity of substances, including epi-demiological studies, will be taken into ac-count,~ The general testing requirements willbe modified to incorporate exposure-driventesting where appropriate,~ Tailor-made testingprogrammes for suh-stances will be developed under the con-trol of authorities for Levell and 2 testing,~ The development of further alternativetesting methods using fewer or no animalswill befostered,

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~ Existing substances will be grouped tominimize testing, where appropriate."

It is planned to replace the current no-tification system for new chemicals by theREACH system, which calls for the Reg-istration, Evaluation or Authorization ofChemicals, depending on their productionvolume and level of concern. It shall beapplied both to new and existing chemi-cals. Among other issues, the productionvolume of the chemical will determine theamount of data required for the market-ing of a specific substance. For substancesproduced or imported in quantities be-tween 1-10 tonnes "data on the physico-chemical, toxicological andecotoxicological properties of the sub-stance" are to be requested and it is stated:"Testing should generally be limited to invitro methods."

When turning the strategy depicted inthe White Paper into a new EU legisla-tion on chemicals, the European Commis-sion has to take into account the com-ments on the White Paper made by theEnvironment and Internal Market Coun-cil and by the European Parliament. TheCouncil of Environmental Ministers dis-cussed the White Paper during their 2355th

session on June T", 2001 in Luxembourg.In conclusion No. 23 published as an out-come of this discussion (Council, Envi-ronment, 2001), the Council underlinesthat: " ... animal testing should be limitedto the level necessary to deliver the ob-jectives of the strategy, including a highlevel of protection for human health andthe environment. Industry should make allexisting data available to avoid duplica-tion of testing. Mechanisms are neededto ensure that unnecessary testing require-ments are avoided. Adequate resourcesmust be provided for research, develop-ment and validation of globally acceptedtest guidelines for alternative in vitro testmethods, so that work can be acceleratedat all levels. Activities under the newFramework Programme for Researchshould consider these requirementsamong its priorities. ln addition to pro-moting this issue in ECVAM, the Commu-nity should playa more active role in theGECD, to encourage wider adoption ofvalidated, alternative, non-animal testingmethods."

In addition, in conclusion No. 40, theCouncil invites the Commission, "to study

how to develop screening procedures toeffectively identify chemicals with poten-tially harmful properties or uses of con-cernfor the purposes of prioritising sub-stances for which further information isurgently needed and those requiring ac-celerated risk management" and (Coun-cil Conclusion No. 42) to " ... study fur-ther the data requirements for substancesproduced in volumes below 10 tonnes inorder to ensure that the information pro-vided will be sufficient for classificationand labeling and to assess the need forrisk reduction measures. The data setsmust also provide appropriate informa-tion for handling cases of unintentionalreleases and to enable the protection ofthe health and safety of workers whilstensuring a minimum of animal testing."

The European Parliament, as of the be-ginning of November 2001, has not yetput forward a final opinion on the WhitePaper. However, a report on the WhitePaper has been prepared by MEP IngerSchorling (European Parliament, 2001),which has been voted on in the Commit-tee on the Environment, Public Health andConsumer Policy of the European Parlia-ment on October 16, 2001. In thisamended but not finalised report, RecitalT states: " ... animal tests must be replacedwith more humane alternatives, and co-ordinated action is needed to bring newnon-animal tests into use." Paragraph 13of the draft report states that the EuropeanParliament "calls on the Commission toensure that animal testing is reduced tothe absolute minimum, firstly by ensur-ing that all existing data is made avail-able and considered, and secondly byimplementing, as far as possible, a step-wise non-animal testing strategy, thatmakes full use of computer models thatpredict hazards based on chemicalstructure (QSAR), as well as of physico-chemical tests for persistency andbioaccumulation, and cascades of in vitrotests, also with a view to reducing testingtime and costs."

3 Ways to implement the promotionof non-animal testing in a newchemicals policy

From the point of view of animal welfarethe deficiencies in the current chemicalspolicy are also an evidence for the short-comings of animal testing strategies, be-

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ing that the testing strategies are either toocumbersome to be pursued on a largescale or that the animal tests performedare not relevant enough to lead to appro-priate decisions. Furthermore the short-comings of the current system are causedby deficiencies in strategies on how tomanage risks caused by dangerous sub-stances.It is the aim of the White Paper to over-

come these problems and to ensure thathuman health and environmental integrityare not put at risk by man-made chemi-cals and at the same time to avoid the useof animal tests. The Environment Coun-cil has confirmed these goals, and it canbe foreseen that the European Parliamentwill also confirm them. However, thesegoals can only be reached if the key ele-ments of the new strategy to "maximise"the use of alternatives, to "minimise" theuse of animal tests, and to achieve "flex-ibility" in testing strategies are furtherelaborated and specified.

3.1 Risk management strategiesThe appropriate starting point for deve-loping a new chemicals policy is the de-velopment of risk management strategies.Before risks are determined through anykind of evaluation, sound risk manage-ment strategies have to be agreed upon.It is imperative that the bodies involveddecide on actions to be taken when spe-cific chemicals are found to have certainhazardous properties. And these decisionshave to be made before chemicals are ac-tually tested and evaluated. In the nextstep, the need for particular types of in-formation has to be identified andprioritised and the appropriate method ofobtaining the necessary information hasto be determined. For example, if the re-sponsible bodies agree that certain prod-ucts would be considered unacceptablewhen found to be bioaccumulative or per-sistent, the determination of these char-acteristics would render further testingsuch as toxicity testing unnecessary.

3.2 Safety testing strategiesNon-animal testing strategies should notappJy to low production volume chemi-cals only, as depicted in the White Paper,but to all levels of production volume. Inorder to avoid animal tests and at the sametime to ensure maximum safety to humansand the environment, the following step-

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wise testing strategy is to be recom-mended in line with the strategy de-manded in the draft report adopted by theEnvironmental Committee of the Euro-pean Parliament:In the first step. all existing information

on the respective substance and on sub-stances with similar structure is to be col-lected, making use of data available in theindustry, with the authorities, and also atscientific and medical centers. In the nextstep, hazard prediction shall be madebased on the structure of the chemical, forexample by means of QSAR models. Thefollowing step covers the evaluation ofphysico-chemical properties and the per-formance of persistency and bioaccumu-Iation tests. Next, a battery of basic in vitrotests is to be applied covering endpointssuch as basal cytotoxicity, in vitro muta-genicity, skin penetration and corrosivity,in vitro metabolism and in vitroecotoxicity. Taking into account the re-sults of this initial battery of in vitro test-ing, in the following step a battery of spe-cific in vitro tests should be applied withthe performance of cell transformationtests and evaluations of the effects on spe-cific cell types such as embryonic stemcells, hepatocytes or neurons.After each step it should be evaluated

if a classification of the respective sub-stance is already possible. For the safetyof humans and the environment, sub-stances that provide reason for concernin non-animal tests should be classifiedaccordingly without further testing. Thequestion of whether an animal test shouldbe performed for the classification of achemical should only be put forward af-ter all possibilities to collect the neces-sary data without animals have been takeninto account. When deciding whether toperform a specific animal test, advicefrom experts in the field of alternativemethods should be sought.

3.3 Waiving mechanismsA clear strategy on when to omit whichtests should be developed tailoring test-ing according to the results of the evalua-tion of existing data, physico-chemicalproperties, the use and the exposure to thesubstance. This strategy should be imple-mented in concrete official guidelines andmust allow every possible opportunity toavoid animal and non-animal testing andto classify a given chemical making use

of the minimum information necessary forthat purpose.

3.4 Funding of alternative testdevelopment and validationIt is scientifically feasible to determinethe relevant toxicological and ecoto-xicological endpoints without animals.However for many endpoints officiallyaccepted non-animal test methods are notyet available. In order to overcome thisdeficit, the status of alternative methodsmust be identified for each relevantendpoint, distinguishing betweenendpoints, for which accepted alternativesexist or, respectively, validated alterna-tives, alternatives in the process ofprevalidation, alternatives in the processof development, or only scientific propos-als on how a specific endpoint could beevaluated without animals.In the White Paper concrete deadlines

for the registration of chemicals have beenset down. Therefore immediate action toclose the respective knowledge gaps isindispensable, if significant progress is tobe made in developing, validating and ac-cepting non-animal test methods in timeto have an impact on the testing to be donein order to meet these deadlines, and asubstantial amount of funding is required.Initially this work should focus on thoseendpoints that will be requested at baseset level and on those tests with the great-est potential to save animals in regard tothe registration of existing chemicals, forexample in vitro sensitisation tests or invitro skin and eye irritation tests.Thus, research in alternative methods

for the testing of chemicals should becomea priority key action in the sixth Frame-work Programme for Research currentlyunder discussion on the level of the Euro-pean Union. The Environment Council hasexplicitly formulated this same request,and reference is made to it in the draft re-port of the European Parliament. In addi-tion, national funding programmes in theEU member states should supplement EUfunding.So far, this demand has only partly been

taken up. In October 2001, the EuropeanCommission (Commission of the Euro-pean Communities, 2001b) has proposeda series of initial research priorities withthe aim of "providing health, security andopportunity to the people of Europe". It isstated that research in this area will focus

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on (amongst other issues) the "develop-ment of improved methods for risk assess-ment, including non-animal test methodsfor chemical substances". Whereas thisstatement is to be welcomed, a specifiedand adequate amount of the researchbudget remains to be designated to thisarea of research in order to ensure thatthe goal will be met.It is to be noted that the task of deter-

mining the current status of alternativemethods for all relevant toxicity testendpoints has been taken up by ECVAM,the European Centre for the Validation ofAlternative Methods of the Joint ResearchCentre of the European Commission. Adocument covering the outcome of theirwork is currently under preparation. Thisdocument should be taken into accountwhen designing testing strategies for thenew chemicals policy and also when de-termining areas of priority for funding inalternative method research and for thefunding of alternative method validationstudies.When validating alternative methods

and when deciding on their acceptability,the hurdles set should not be higher thanthose set for the acceptance of animaltests. In order to speed up the acceptanceof new alternative methods, the requestof the Environment Council, that the Eu-ropean Commission should play a more

active role on the level of the OECDshould be taken into regard. In additionclassifications schemes for the relevantendpoints applicable to the respective al-ternative test methods have to be designedand agreed upon.

4 Conclusions

In the White Paper for a future chemicalspolicy in the European Union a high goalhas been set, that is to design a new policythat will improve the safety for humansand the environment and at the same timeto minimise animal testing. It is possibleto reach this goal if all responsible bodiesand organisations involved cooperate andstrive to reach the objectives laid down inthe White Paper. However, a lot remainsto be done, and substantial financial sup-port is needed.

References

Commission of the European Communi-ties (1998). Report on the evaluation ofthe EU legislation on industrial chemi-cals. Commission Working DocumentSEC(1998) 1986 final.

Commission of the European Communi-ties (2001a). White Paper- Strategy forafuture Chemicals Policy. COM(2001)88final. February 27,2001.

Commission of the European Communi-ties (2001b). Amended proposal for aCouncil Decision concerning the spe-cific programme 2002-2006 for re-search, technology development anddemonstration aimed at integratingand strengthening the European re-search area. COM(2001) 594final.October 17, 2001.

Council, Environment (2001). Report on2355th Session of the Council "Envi-ronment" , Luxembourg, 7 June 2001.

Danish Board ofTechnology (1996). Thenon-assessed chemicals in EU. Reportand recommendations from an interdis-ciplinary group of Danish experts.ISBN: 87-90221-1 0-9.

European Parliament (2001). Draft Reporton the Commission White Paper onStrategy for a future Chemicals Policy.Committee on the Environment, PublicHealth and Consumer Policy. Rappor-teur Inger Schorling. Provisional 2001/2118(COS), 24 July 2001.

Correspondence addressDr. med. vet. Ursula G. SauerAkademie fur TierschutzSpechtstrasse 1D-85579 NeubibergTel.: +49 89 600 201 0Fax.:+498960029115ursula.sauer@tierschutzakademie.de

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