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ealth effects and the environmental impacts should be considered.he implementation of Human Health Risk Assessment methodol-gy, through the construction of environmental health indicatorsntegrated with the technological processes of the oil and gas indus-ry can be an efficient strategy to provide a holistic approach for thisector.

This strategy also contributes to understand how and why tossess the human health effects at beginning of the first stages ofhe Environmental Impact Assessment (EIA) will be an essentialnowledge base needed to respond effectively and quickly to thehallenge of the energy sector.

The use of integrated indicators for health and environmenty the industries has acquired an enormous importance in thentrepreneurial sustainable development. The complexity of theealth and environment problems, that our generation and futurenes to come need to address, will continue to increase. Theemand and urgency for decisions and solutions will also continueo grow, so the identification and framing of new approach willrovide tools for the challenges scientific and the integrative needf health and environment issues.

The relationship study of cause and effect between the expo-ure to several environmental agents and the respective humanealth impacts should consider the application of the toxicology,pidemiology, and the human health risk management, where theevelopment and the use of environmental health indicators havevery relevant contribution. This methodology finds some diffi-

ulties related to the financial and information limitations, as thehortage and the quality of the available data and the uncertaintiesue to the aggregation of reports from several areas and sections,s the oil, gas and energy industry.

oi:10.1016/j.toxlet.2010.03.367

106-031isk assessment of synthetic food color exposure in Thaiopulation

. Benjapong, S. Srianujata, A. Nitithamyong, W. Karnpanit, P.isetchat, J. Wonglek, R. Peeratikorncharoenkul

Institute of Nutrition, Mahidol university, Thailand

he standard of synthetic food colors has been established by thehai Food and Drug Administration based on General Standard forood Additive (GSFA). However, food habits vary from country toountry. This study assesses risk from the exposures of syntheticood colors based on the maximum use levels of the GSFA and theeal exposure in the Thai population in order to conform food safetyo international standards and to improve national food safety. Theisk was estimated following the standard methodology for riskssessment of food additives recommended by the Joint FAO/WHOxpert Committee on Food Additives (JECFA). The assessment wasone by comparing the estimated exposure of synthetic food coloro the Acceptable Daily Intake (ADI). The real exposure was assessedn school children from three provinces of Thailand. The exposuresstimated from all food categories using color additives based onhe maximum use levels that are considering in all steps of theodex commodity indicated that Thai children were exposed to 7ynthetic food colors, including carmoisine, ponceau 4R, erythro-ine, riboflavins, tartrazine, sunset yellow and indigotine aboveheir ADIs. Thus it should reduce the maximum use levels of these

olor additives in some food categories based on the health risknd technological justification. However probabilistic risk estima-ion of the real exposure indicated that the average intake of eachynthetic color found in food which students preferred to consume

196S (2010) S37–S351 S103

did not provide adverse effects because the degree of exposure waslower than the ADI. But higher risk was observed in extreme intake(95th percentile) of food containing high levels of synthetic foodcolors, especially in the color for which JECFA has established a lowADI value including erythrosine and sunset yellow.

doi:10.1016/j.toxlet.2010.03.368

P106-032CEFIC-LRI workshop on skin sensitisation methods: Workshopreport

J.C. Carrillo 1, D. Eigler 2, P. Kern 3, R. Kreiling 4, M. Woolhiser 5

1 Shell International, Netherlands, 2 Evonik Goldschmidt GmbH,Germany, 3 Procter & Gamble Eurocor, Belgium, 4 Clariant Produkte(DE) GmbH, Germany, 5 DOW Chemical Company, USA

Skin sensitisation is an important toxicological endpoint thatis assessed for all chemicals. Currently, two in vivo OECD testguidelines are used to assess this hazard for regulatory purposes.The more recently developed LLNA (OECD 429) is the prescribedmethod under REACH over the traditional guinea pig tests (OECD406). In the context of animal welfare benefits and the ease ofpotency quantification, the LLNA is commonly regarded as the ‘goldstandard’ for sensitisation testing.

Repeated discrepancies between the results obtained with theLLNA and guinea pig tests have been reported for certain classes ofchemicals (e.g. surfactants, unsaturated fatty acids, and siloxanes).Such substances are not thought to be sensitising based on years oftest results and a lack of human experience. These results suggest aneed for improved characterization of test results to enable a betterunderstanding of potential confounding chemistries.

In order to broaden the awareness among stakeholders a CEFICLong-range Research Initiative workshop was organized to presentand discuss these experiences with a panel of experts from regu-latory, academic and industrial organizations. Focused discussionsinvolved the definition of a ‘gold standard’, applicability domainsand the use of LLNA, guinea pig and human experiences for thedevelopment of next generation tests.

The findings and recommendations of the workshop will serveas a guide in a research strategy to understand critical aspects ofthese test results and the development of reliable alternative meth-ods, while advancing a flexible and intelligent skin sensitisationtesting strategy across different chemical classes.

doi:10.1016/j.toxlet.2010.03.369

P106-033Refinement of the dermal sensitisation threshold for skinsensitisation

B. Safford, N. Gilmour, N. Aptula

SEAC, United Kingdom

In a recent publication [1] the concept of the Dermal Sensitisa-tion Threshold (DST) was proposed, based on the principles of theTTC. In that paper a probabilistic analysis was presented basedon an understanding of the incidence of sensitisers in the world

of chemicals and the distribution for sensitisation potency basedon published Local Lymph Node Assay data. From the analysis ofthese data sets it was concluded that a DST could be establishedbelow which there is no appreciable risk of sensitisation, even for anuntested ingredient. Use of a DST would preclude the need for sensi-

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isation testing of ingredients where dermal exposure is sufficientlyow.

Further work has now been conducted to refine the DST pro-ess such that it can be used confidently as a risk assessment tool.he additional work described in this presentation consists of theollowing steps:

. Expanding the dataset used in the original published DST anal-ysis to investigate whether the distribution of potencies ofsensitisers would hold true when additional chemicals areadded.

. Investigation of whether the use of mechanistic chemistrydomains could improve the robustness of the DST methodology.

Based on this work it is concluded that classification of mech-nistic chemistry domains based on structure provides a usefulechanism of refining the DST and, for chemicals that are pre-

icted to be non-reactive to proteins, a DST can be establishedelow which there is a very small chance of an untested mate-ial posing a skin sensitisation risk. This DST value for non-reactivehemicals is higher than the DST originally determined, and at theame time provides a higher level of comfort. Chemicals which areredicted to have a protein binding potential would need to be riskssessed on a case-by-case basis.

eference

afford, R.J., 2008. Regul. Toxicol. Pharmacol. 51, 195–200.

oi:10.1016/j.toxlet.2010.03.370

106-034eer-reviewing of herbal medicine toxicity test reports underhe Korean National Toxicology Program

.J. Yu 1, M.S. Dong 2, J.Y. Lee 1, J.H. Lee 1, M.C. Moon 1, C.S. Kang 1,.S. Han 1, M.H. Kang 1

Hoseo University, South Korea, 2 Korea University, South Korea

he Korean National Toxicology Program (KNTP) was establishedn 2001 as a multi-disciplinary program supported by the Koreanood and Drug Administration (KFDA). The objectives of KNTP areo prevent human health from toxic chemical exposure, and to pro-ide science based toxicity information to citizens to keep any socialisturbance from the invalid toxic information. The activities of theNTP include: sponsoring chemical toxicity testing, establishing

oxicity evaluation infra-structure, developing alternative testingethods, building toxicity database with integrated toxic chemi-

al management program, organizing inter-ministerial cooperativerogram, and initiating toxicology research centers to evaluateoxic chemicals in depth and systemic. The toxic substances anderbal medicines will be selected, tested, and monitored throughhe KNTP and finally utilized for assessing the risk of the substances.he typical KNTP toxicity battery was consisted of 14–90 daysepeated dose toxicity tests, genotoxic tests including Ames test,hromosomal aberration, and in vivo micronucleus test. Especiallyoxicity test reports for herbal medicines that were suspected forheir toxicity were peer-reviewed annually by the expert panel con-isting of specialists in exposure, animal experiment, epidemiology,

nd mechanism. After peer-reviewing, the review panel submitsechnical reports both in Korean and English. These activities even-ually will be helpful in improving public health and regulatoryolicy. The KNTP is also interesting in establishing internationalooperation program to share the toxicology program experiences

196S (2010) S37–S351

with other countries and to collaborate toxicity assessment activi-ties.

doi:10.1016/j.toxlet.2010.03.371

P106-035Ethical considerations of acceptability of biological samplingby participants in a research study

N. Noisel, C. Caux, G. Carrier, M. Bouchard

University of Montreal, Canada

Acceptability of biological sampling is always a consideration whenestablishing a research protocol. In a controlled research studylooking at the time course of selenium in biological matrices fol-lowing a 1-month therapeutic shampoo treatment, ten healthyuniversity volunteers were asked to provide repeated blood, urineand hair samples. Blood samples were collected by a nurse over a3-month period, once a week during treatment and once every twoweeks over two months post-treatment. With a similar sequence,volunteers were asked to provide ∼12 h urine collections. Duringthe 3-month study period, two hair samples were also taken fromthe root. At the end of the study, volunteers were invited to fill aself-administered questionnaire to document their perception andacceptability of sampling methods.

Most volunteers reported that repeated blood sampling was theless annoying and that repeated 12 h urine collections were moreinconvenient. In fact, 12 h urine collections were reported to be con-straining (necessity to stay at home, leave the bottle in the fridge)and not well perceived by other people around. Transport is alsodelicate (public areas, risk of spills). On the contrary, volunteersreported that blood sampling took little time, was facilitated by thefact that the appointment with the nurse was set in advance and itwas not necessary to remember any procedure key points. As forhair sampling, most volunteers were more reluctant for aestheticreasons.

This exploratory survey initiates a reflection concerning theacceptability of biological sampling. Factors such as age, educa-tional level, research protocol and other context elements caninfluence sampling acceptability in volunteers. Acceptability andrisk perception by volunteers should also be considered by ethicsboards, to define what is ethically acceptable or induces a risk ofprejudice. These aspects should be further investigated in futurebiomonitoring studies, especially those implying multiple sam-plings.

doi:10.1016/j.toxlet.2010.03.372

P106-036REACH regulation (EC) 1907/2006: A survey of companiessituation in view of the first registration deadline

R. Butera 1, A. Caldiroli 1, C. Osnaghi 2, A. Sacchi 3, L. Manzo 1

1 IRCCS Maugeri Foundation and University of Pavia, Italy,2 InterConsortia, Milan and Bruxelles, Italy, 3 Sacchi Consulting, Milanand Bruxelles, Italy

In view of the first deadline for registration of phase-in chemicals

according to REACH Regulation (EC) 1907/2006, a questionnairewas sent in January 2010 to the Italian members of InterConsor-tia, a transversal consortium mainly addressed to distributors andimporters. The questionnaire was developed in order to determineif and to what extent companies had already undertaken actions to