1. Health and Safety Executive UK Approach to Risk Assessment of Genotoxic Carcinogens in the Occupational Setting Dr Susy Brescia Chemicals Regulation Directorate

2. Setting the scene For some chemicals/uses (cosmetics, biocides for the amateur, food additives, etc), mutagenic property sufficient to ban/not authorise use by the general public no risk assessment required; For industrial/professional uses of chemicals with a mutagenic property, societal position has been not to ban, but to seek to manage the risk risk needs to be considered.

3. Legal framework for industrial/professional uses of chemicals Chemical Agents Directive; Carcinogens Directive; REACH; Classification, Labelling and Packaging Regulation;

4. Genotoxic carcinogens: definition Induce tumours, increase tumour incidence and/or malignancy or shorten time to tumour occurrence in animals or humans; Evidence of mutagenic activity in vivo; Assumption made – genotoxicity key event in mechanism of carcinogenesis

5. Genotoxic carcinogens: identifiable threshold or not identifiable threshold? Increasing evidence even directly acting genotoxicants have (rather than can be postulated to have) a biological threshold – difficult to identify experimentally; Where mechanistic data available and practical dose threshold identified RA according to threshold approach; Where threshold cannot be identified – we do not know whether a threshold exists (any exposure might carry some risk);

6. UK approach to RA of non (identifiable)- threshold genotoxic carcinogens A safe level of exposure cannot be identified; No attempt to quantify levels of risk; ALARP: reduce exposure ‘As Low As is Reasonably Practicable’;

7. UK approach: why no quantification of risks?

8. ALARP Not a risk assessment methodology; Risk management tool; Emphasis on adequacy of controls to achieve sufficiently low level of exposure at which there could still be a level of cancer risk, but if so, the judgement is that it is low; To ensure exposure is reduced at the lowest achievable and reasonably practicable level;

9. Lowest Reasonably Practicable Level In theory, balance between costs of controls and health benefits; In practice, as no estimation of risks, ALARP has been as low as possible without astronomic costs/closure of business; Or According to REACH, in principle, level at which socio-economic benefits of the substance outweigh the risks; In practice, as no risk estimation in the UK, difficult to implement it in transparent manner; But At this level still continuing duty on industry towards improved control

10. Benefits and disadvantages of ALARP BENEFITS Simple - based on hazard identification and exposure control; No concerns about accuracy of risk estimates; Regulators not forced to defend inaction at “acceptable/tolerable” levels of risks (10 -6 is 200 in 20 million); DISADVANTAGES Not completely transparent; No absolute reference point – best practice tends to be current practice that is best;

11. ALARP in practice in the workplace (1) Elimination/total ban (M+U restriction/REACH restriction from 1 June 09) - technically and economically viable, less hazardous substitutes (underlying principle of CAD, Carc Dir and REACH) REACH Authorisation of nominated SVHCs (including genotoxic carcinogens): Industry to show - Invest in research of safer alternatives; - Develop substitution plan; - Continuing duty to improve controls;

12. ALARP in practice in the workplace (2) Very high level of containment - Closed automated systems; - Redesign of the process; - Engineering controls e.g. equipment under negative pressure; - Regularly cleaned and maintained equipment; - PPE (appropriate gloves, respirators and goggles) and LEV for system breaches (sampling, packing, maintenance/repair); But - Some processes less efficient/do not work when enclosed; - Costs for closed systems may be too high for small companies;

13. ALARP in practice in the workplace (3) Other measures to control risks - Dust and mist suppression methods (e.g. tablets or pellets rather than powder); - Control of staff to work area; - Change of PPE regularly; - Training of employees in the handling of dangerous chemicals; - Air and biological monitoring to show exposure levels are low and PPE is working; - Health surveillance;

14. RA of genotoxic carcinogens: some personal thoughts Unless dramatic scientific advance in developing methods to identify thresholds for genotoxicants, regulatory system has no magic solution to offer; Both qualitative and quantitative approaches based on assumptions and not facts – hence inherently faulty; Question From what we know today on the mechanisms of gentoxicity, is it time to push the boundaries?

15. Is there a satisfactory alternative to ALARP? ApproachProblems ALARPNot transparent No absolute reference point Modelled and model-free linear extrapolation Highly uncertain risk estimates of no biological validity MoE/Large AF (acceptable MoE/AF of 10,000) Not practical in the workplace Practical thresholdCurrently applicable to very few genotoxic carcinogens

16. Health and Safety Executive THANK YOU