Equivalence limit scaled differences for untargeted safety assessments: Comparative analyses to guard against unintended effects on the environment or human health of genetically modified maize.

Safety assessments guard against unintended effects for human health and the environment. When new products are compared with accepted reference products by broad arrays of measurements, statistical analyses are usually summarised by significance tests or confidence intervals per endpoint. The traditional approach is to test for statistical significance of differences. However, absence or presence of significant differences is not a statement about safety. Equivalence limits are essential for safety assessment. We propose graphs to present the results of equivalence tests over the array of endpoints. It is argued that plots of the equivalence limit scaled difference (ELSD) are preferable over plots of the standardised effect size (SES) used previously for similar assessments. The ELSD method can be used either with externally specified equivalence limits or with equivalence limits estimated from (historical) data. The method is illustrated with two examples: first, environmental safety of MON810 Bt maize was assessed using field trial count data of arthropods; second, human safety of herbicide tolerant NK603 maize was assessed using haematological, biochemical and organ weight data from a 90-day rat feeding study. All assessed endpoints were classified in EFSA equivalence categories I or II, implying full equivalence or equivalence more likely than not.

Uptake of azoles by lamb's lettuce (Valerianella locusta L.) grown in hydroponic conditions.

An uptake and translocation study of azole compounds was performed in lamb's lettuce (Valerianella locusta L.) grown in nutrient solution fortified with different azoles. Three azoles, (clotrimazole, fluconazole and propiconazole), which have different physico-chemical properties and are ubiquitous in the aquatic environment, were the compounds selected. An analytical method, based on matrix solid phase dispersion (MSPD) followed by LC-MS/MS determination, was developed to quantify these compounds in aqueous solution and in roots and leaves. The physicochemical properties of azoles are the main factors governing the uptake and plant accumulation. These azoles were detected in leaves indicating their transport within lamb's lettuce. Translocation from nutrient solution to the aerial part of lamb's lettuce was found to be highly dependent on the hydrophobicity of the azole. Clotrimazole accumulates in roots causing necrosis in roots and leaves, whereas fluconazole was the azole with the highest concentration in leaves without causing apparent phytotoxicity symptoms. The assessment of the levels of these azoles in leaves indicates that the risk for human health is negligible.