Application of the TT21C strategy to safety assessment using genetic toxicology as a case study

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S132 Abstracts / Toxicology Letters 229S (2014) S40–S252

Assessment of risk to human health when exposed to pesticidesbased on principles of assessment of potential and real danger intheir total entry into a human body with food, water and air.

In assessing the potential risk of pesticides on the basis ofsanitary-toxicological studies and analysis of the literature, takinginto account the criteria for evaluating toxic, specific and long-termeffects (embryotoxic, teratogenic, mutagenic, carcinogenic, aller-genic and reproductive toxicity), with the limiting value of adverseeffect, a hazard class is being established.

Development of hygienic standards in Russia is carried out usingthe principle of integrated hygienic regulation in which the totalamount of an active ingredient of a pesticide entering a body fromdifferent sources (food, water and atmospheric air) must not exceedADI for humans.

Analysis of residues content of studied pesticides in productsamples at maximum application rate and frequency of treatmentsfor 2 seasons, taken from 3 soil-climatic zones of Russia is beenconducted.

Exposure assessment is an important step in the risk assess-ment when a quantitative entry of a xenobiotic to a human body isestablished.

Determination of exposure levels for risk assessment and riskmanagement allows to set the following:

- populations with high and low exposure levels;- the contribution of various sources of pollution into exposure

levels;- priority action to reduce exposure level and compliance of these

measures with achieving safe to health levels of exposure.

The said methodical approach was tested on pesticides derivedfrom atranilamidos and acetochlor.

http://dx.doi.org/10.1016/j.toxlet.2014.06.469

P-2.124Application of the TT21C strategy to safetyassessment using genetic toxicology as a casestudy

Yeyejide Adeleye 1,∗, Clewell Rebecca 2, Melvin Andersen 2, BinSun 2, Andrew White 1, Paul Carmichael 1, Dent Matt 1, FowlerPaul 1

1 Unilever, Sharnbrook, UK, 2 The Hamner Institutes for HealthSciences, NC, USA

The US National Academy of Sciences/National Research Coun-cil report on TT21C (Krewski et al., 2010) proposes an approachto toxicity testing that could ultimately negate the requirement togenerate hazard data in animals. At the core of this vision is the useof in vitro approaches to investigate perturbations in the critical cel-lular processes that lead to adverse events (toxicity pathways), anda safety assessment approach that ensures human exposure is keptbelow the level that is expected to cause adverse effects. Our organi-zations have been collaborating to investigate what this type of riskassessment may look like in practice for an ingredient in a consumerproduct, using the p53 DNA damage repair pathway as a prototypetoxicity pathway. This pathway was chosen for its known relation-ship to the development of human cancer. We have used a varietyof techniques to determine perturbations in this pathway in humancell lines, investigating both adverse outcome (micronuclei for-mation) and biomarkers such as H2AX and TP53. Computationalmodels of the circuitry of the p53 pathway have been constructedto attempt to characterize the dose–response of these changes.Finally, physiologically based kinetic models describing exposure

to our case study chemical have enabled us to perform an in vitroto in vivo extrapolation, and so compare changes in the pathwaywith expected human exposure in tissues and plasma arising fromconsumer use of the product.

http://dx.doi.org/10.1016/j.toxlet.2014.06.470

P-2.125Optimized ultrasound-assisted dispersiveliquid–liquid microextraction for simultaneoustrace multielement determination of heavymetals in environmental water samples byICP-MS

Xiaojun Wang 1, Jingjing Chen 1, Ying Zhou 1,2,∗, Lijia Wang 1

1 College of Chemical Engineering, Zhejiang University of Technology,Hangzhou, Zhejiang, China, 2 Research Center of Analysis andMeasurement, Zhejiang University of Technology, Hangzhou,Zhejiang, China

In recent years, the environmental pollution by heavy elementshas been dramatically increased and developing an efficient andsimple method for determination of heavy metals in environmentalwater samples is a very important task. As one of miniatur-ized separation and extraction techniques, dispersive liquid–liquidmicroextraction (DLLME) has been widely applied in the fieldof environmental monitoring and assessment. In this study,a simultaneous trace multielement determination method wasdeveloped for Zn, Co, Cu and Ni in environmental water samplesusing ultrasound-assisted dispersive liquid–liquid microextraction(UADLLME) method, followed by inductively coupled plasma-mass spectrometry (ICP-MS). Diethyldithiocarbamate (DDTC) andcarbon tetrachloride were selected as the chelating agent andextraction solvent. Several parameters that affect the extractionefficiency, such as the volume of the extraction solvent, pH of sam-ple solution, concentration of the chelating agent, salt effect, andsonication time were investigated and optimized. Under the bestexperimental conditions, the limits of detection (LODs) for Zn, Co,Cu and Ni were 0.034, 0.048, 0.017, 0.028 �g L−1, respectively. Thelinear dynamic range for Zn, Co, Cu and Ni was 0–250 �g L−1 andthe correlation coefficient (R2) was higher than 0.9997. The relativestandard deviations (RSDs, C = 50 �g L−1, n = 7) were in the range of2.1–3.6%. The relative recoveries at the spiking level of 50 �g L−1

were between 92% and 99%. The method was successfully appliedto determination of Zn, Co, Cu and Ni in tap, river and lake watersamples.

http://dx.doi.org/10.1016/j.toxlet.2014.06.471

P-2.126Identification of the most common pathogensformed by environmental fungus toxins inhuman’s eye

Alireza Ebadollahinatanzi 1,∗, Gholamreza Arabrahmatipour 2,Seyed Ali Tabatabaei 3

1 The Institute of Applied Scientific Education of Jihad-e-Agriculture,Imam Khomeini Higher Education Center, Karaj-Tehran, Iran,2 Farabi Hospital Laboratory, Medical Sciences of Tehran University,Tehran, Iran, 3 Emergency Ward, Farabi Hospital, Medical Sciences ofTehran University, Tehran, Iran

Objectives: Presently our information regarding to pathogenicmicroorganisms and their producing toxins are in progress.