ology 2

94 Abstracts / Toxic

packages were used to cover 13 substances, bring-ing potential animal use down from around 900 to<300. Over recent years, use of read across in the UKhas avoided the use of many thousands of animals.

(3) Identification of possible reductions in animal num-bers, through collation of the test results submittedby notifiers. For example, when the minimum groupsizes specified by the OECD guideline for the guineapig maximisation test were halved, based on findingsfrom HSE experience with new chemicals, the sav-ings since 1993 in the UK alone amount to over 5300guinea pigs.

(4) Lessening of the testing requirements for certaintypes of regulatory situation. Until June 2003, forexample, HSE used to require a basic package ofinformation, usually derived from up to four par-ticular animal tests, for well-controlled substancessupplied solely for research purposes. This require-ment has now been waived with over 5000 animalsspared to date.

(5) Opposition to proposals to increase animal testingrequirements, where the potential human health ben-efit is outweighed by the animal welfare costs. Thus,in 1993 HSE raised strong concerns within the EU toprevent the addition of an animal-based reproductivetoxicity screen to the basic notification requirementfor new industrial chemicals. In the UK alone thishas avoided the use of several thousand animalsevery year since.

(6) Consideration of available toxicological informationand human exposure patterns to minimise the addi-tional testing generally required for high tonnagechemicals. For example, no further testing might berequired if there is little toxicological concern fora particular end-point, and experience in the use ofthe chemical indicates human exposure to be negligi-ble. Use of this sort of approach reduced animal usefor the nine highest-tonnage substances from about21,000 to 7300.

(7) Encouraging the early use of refined methods. Forexample, when the OECD guideline for the locallymph node assay for skin sensitisation was pub-lished in 2002, HSE informed notifiers that conductof the previously predominant guinea pig max-imisation test would require full justification ona case-by-case basis. In practice, conduct of themaximisation test to support UK new substance noti-fications is now very rare.

Whilst further development of alternative methodsfor full replacement of animals in regulatory testingis still required in many areas, it is also the case that

31 (2007) 91–99

other approaches such as those described above, to bringreductions and refinements, provide a valuable means ofimproving the situation in the shorter term.

doi:10.1016/j.tox.2006.11.014

Exposure driven testing to minimize animal use

Mike Comber ExxonMobil, Belgium

Under the terms of the proposed REACH legislation,all substances will need to provide a defined level ofinformation, dependant upon tonnage of use. Althoughthere are various descriptions within the legislation thatsuggest that testing may be waived based on exposure,the conditions for this waiving are not defined. Over thelast 3 years, there have been a number of activities whichhave attempted to describe what “Exposure Based Waiv-ing/Trigger” of tests could entail. A number of proposalshave been outlined by ECETOC in the Targeted RiskAssessment report and the Alternatives in EnvironmentalEndpoints report as well as the REACH ImplementationProject 3.2.1 scoping study.

doi:10.1016/j.tox.2006.11.015

Implementation of screening approaches to minimiseanimal use

Robert L. GuestE-mail address: rguest@safepharm.co.uk.

Safepharm Laboratories Ltd., P.O. Box 45, DerbyDE12BT, United Kingdom

The 3Rs of Russell and Burch have become a pri-mary consideration when designing toxicological studyprotocols or programmes of work. However, adoptionof the 3Rs can present significant challenges when thetoxicological assessment is required to satisfy a specificregulatory requirement, as there may be limited scope todeviate from official test methods. Adoption of replace-ment methods has to be the ultimate goal, but this ispossible only after formal validation of the method andregulatory acceptance. There have been a number of suc-cesses with respect to replacement, but these have mainlybeen for evaluation of the more simple endpoints. Wherereplacement has not yet been achieved, other strategies,such as screening approaches, can be employed to min-imise animal usage and severity of procedures. This is not

a new concept, but with the increasing pressures to testmore and more substances and at the same time reduceanimal usage, greater importance will be placed on theseapproaches.