372 British Toxicology Society Abstracts, Spring 2

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Cytotoxic effect of dibutylphthalate and/or methomyl on cere-bellum and cerebrum of male albino rats

doi:10.1016/j.tox.2010.08.133

TP

ig. 1. Increase in p53 expression in GSTP1/2(−/−) mice. Whole cell lysates from 10-eek-old mice on a 129xMF1 background were analysed by western blotting usingprimary antibody for p53.

ism may exist between p53 and GSTP, and this is currently beingnvestigated further.

eference

dler, V., Yin, Z., Fuchs, S.Y., et al., 1999. EMBO J. 18 (5), 1321–1334.enderson, C.J., Smith, A.G., Ure, J., et al., 1998. Proc. Natl. Acad. Sci. U.S.A. 95 (9),

5275–5280.itchie, K.J., Henderson, C.J., Wang, X.J., et al., 2007. Cancer Res. 67 (19), 9248–9257.itchie, K.J., Walsh, S., Sansom, O.J., et al., 2009. Proc. Natl. Acad. Sci. U.S.A. [Epub

ahead of print].u, Y., Fan, Y., Xue, B., et al., 2006. Oncogene 25 (42), 5787–5800.

oi:10.1016/j.tox.2010.08.131

52

EACH: The need for a truly multidisciplinary approach towardshe integration of toxicological, epidemiological and environ-

ental sciences with socio-economic analysis

hilip Holmes ∗, Meg Postle, Nigel Tuffnell, Daniel Vencovsky,anos Zarogiannis

Risk and Policy Analysts, Loddon, Norfolk NR14 6LT, United Kingdom

-mail address: philip.holmes@rpaltd.co.uk (P. Holmes).

REACH (EC 1907/2006) is now in force and aims to improveuman/environmental protection by requiring risk assessmentsRA) on chemicals. The initial step, Registration, is intended toather hazard, use and exposure data to inform a RA. Manage-ent options are then considered to ensure adequate control. For

able 1otential impact of a ban on cadmium in brazing alloys in Europe (from RPA, 2009).

Endpoint Potential saving

Number cases avoided

Lung cancer in professional users inEU15

6–29 deaths/year (using AF and CAREX)

Emphysema in professional users inEU15

9 cases/year (from HSE incidence rates andEU15 worker data)

All cause deaths (age-standardised) inheavy hobby users

0.08–0.155 cases/year in heavy hobby user(based on risk association between urinarylevels and death rate)

010 / Toxicology 278 (2010) 341–378

some substances of very high concern (SVHC)’ or those that pose asignificant risk at an EU level, individual uses may require ‘autho-risation’ or be subject to ‘restriction’. Part of these processes is asocio-economic analysis (SEA) to establish the balance betweenthe overall benefits and costs of regulatory actions. These SEAsrequire consideration of available hazard and exposure informa-tion and comparison of the benefits with the costs from usingalternative chemicals or processes. Methods to facilitate such cross-disciplinary analysis are poorly developed. Using SEA techniquesas a starting point, several ‘real world’ examples are being devel-oped (e.g. polybrominated flame retardants, 1,4-dichlorobenzene,chromium VI and cadmium (Cd)). For each, toxicological, epidemio-logical and ecotoxicity assessment techniques are used to estimatethe adverse impact(s) from use of the chemical and to estimatehow this may change under various regulatory scenarios. To theextent possible, the estimated health and environmental ‘savings’from introducing regulatory measures are then converted to moneyvalues and compared with estimated costs of introducing restric-tions on use using various socio-economic techniques; an exampleis given for Cd in Table 1. When completed, the study will informthe process of combining RA with SEAs under REACH to facilitaterobust, science-based policy decisions to be made.

Acknowledgements: This work draws on a series of projectsfunded by the European Commission.

Reference

RPA, 2009. Socio-economic impact of a potential update of the restric-tions on the marketing and use of cadmium. Risk and Policy Analysts,Published on line by DG Enterprise at: http://ec.europa.eu/enterprise/sectors/chemicals/files/markrestr/study cadmium dec09 en.pdf.

doi:10.1016/j.tox.2010.08.132

P53

Potential cost to industry (D , million)

Present value estimate(discount over 20 years; D ,million)

97.85–472.94 D 57.8–352 over 20 years(estimated using cost-benefittechniques)0.13

sCd

1.3–3.79