Indicator Of Potential Toxicity Research Articles

Reduction of Fumonisin Toxicity by Extrusion and Nixtamalization (Alkaline Cooking)

Fumonisins are mycotoxins found in corn. They are toxic to animals and cause cancer in rodents and neural tube defects in LM/Bc mice. Reducing their concentrations in corn-based foods is therefore desirable. Chemical analysis or in vitro bioassays of food extracts might not detect toxic fumonisin reaction products that are unknown or unextractable from food matrices, thus potentially underestimating in vivo toxicity. The effectiveness of two common cooking methods, extrusion and nixtamalization (alkaline cooking), to reduce the toxicity of fumonisin-contaminated corn grits (extrusion) and whole kernel corn (nixtamalization) was shown by means of rat feeding bioassays using fumonisin-specific kidney effects as indicators of potential toxicity. A third bioassay showed that in contrast to fumonisin B1 (FB1), hydrolyzed fumonisin B1 (HFB1; formed from FB1 during nixtamalization) did not cause neural tube defects in LM/Bc mice. The findings indicate that extrusion and nixtamalization reduce the potential toxicity of FB1-contaminated corn.

Tissue accumulation of aluminium is not a predictor of toxicity in the freshwater snail, Lymnaea stagnalis

The amount of toxic metal accumulated by an organism is often taken as an indicator of potential toxicity. We investigated this relationship in the freshwater snail, Lymnaea stagnalis, exposed to 500 μg l −1 Al over 30 days, either alone or in the presence of phosphate (500 μg l −1 P) or a fulvic acid surrogate (FAS; 10 mg l −1 C). Behavioural activity was assessed and tissue accumulation of Al quantified. Lability of Al within the water column was a good predictor of toxicity. FAS increased both Al lability and behavioural dysfunction, whereas phosphate reduced Al lability, and completely abolished Al-induced behavioural toxicity. Tissue accumulation of Al was not linked to toxicity. Higher levels of Al were accumulated in snails exposed to Al + P, compared to those exposed to Al alone, whereas FAS reduced Al accumulation. These findings demonstrate that the degree of tissue accumulation of a metal can be independent of toxicity.

Prospective, Randomized, Controlled Evaluation of a Gentamicin Loading Dose in Neonates

A prospective, randomized, controlled evaluation comparing a 4-mg/kg loading dose (LD) of gentamicin to the standard regimen of 2.5 mg/kg every 12, 18 or 24 h was conducted in critically ill neonates. The objective of the study was to compare the time required to achieve a therapeutic peak serum concentration (i.e. the number of dosing intervals) and to compare the number of serum concentrations outside the therapeutic range as an indicator of potential toxicity between the treatment groups. Eighteen of 26 patients, 5 of 13 in the control group and 13 of 13 in the LD group (p = 0.012) achieved an initial peak concentration of > or = 5 micrograms/ml following the first gentamicin infusion. There were no significant differences between the control and LD group in the number of potentially toxic serum concentrations. When patients were subdivided according to gestational age (GA), patients of < or = 34 weeks had significantly lower initial peak concentrations. A LD of 4 mg/kg in neonates, particularly those of < or = 34 weeks GA, produced a therapeutic peak concentration following the initial dose. There is a minimal risk of attaining serum concentrations commonly associated with toxicity providing the dosage interval is adjusted based on serum creatinine determinations. Based on this study, infants of > 34 weeks GA generally achieve therapeutic peak concentrations after the first dose with conventional dosing; however, in younger infants an appropriate LD is required to reach therapeutic concentrations early in therapy.

Similarities in the Mechanisms of Antibacterial Activity (Microtox™ Assay) and Toxicity to Vertebrates

The structural determinants associated with inhibition of bacterial growth (Microtox assay), as well as those associated with other toxicological activities, were identified using the CASE/Multi-CASE structure-activity relational system. CASE/Multi-CASE also possesses the ability to compare structural determinants associated with different biological phenomena. The extent of the homology between structural determinants can be used to evaluate common mechanisms of action. Using this approach, significant commonalities between structural determinants associated with the Microtox assay and those associated with toxicity to mammals and fish were found, suggesting that there may be a mechanistic relationship between these toxicological activities. The findings indicate that, within these structural similarities, the Microtox assay can be used as an indicator of potential toxicity to mammals and fish.

Accumulation, regulation and toxicity of copper, zinc, lead and mercury in Hyalella azteca

Zinc, lead and mercury accumulation in the amphipod Hyalella azteca increases with increasing exposure to metals. During 10 week chronic toxicity tests, metal accumulated at the highest non-toxic/lowest toxic concentration was 126/136 µg Zn g−1, 7.1/16 µg Pb g−1 and 56/90 µg Hg g−1 dry weight. Concentrations of lead and mercyry in control animals were substantially lower (1.3 µg Pb g−1 and 0.4 µg Hg g−1), but concentrations of zinc in controls (74 µg g−1) were about one half those of the lowest toxic concentration. Copper was completely regulated. Accumulated copper concentrations after 10 weeks exposure to all waterborne copper concentrations resulting in less than 100% mortality were not significantly different from controls (79 µg g−1). Lead and mercury concentrations in wild H. azteca should be useful indicators of potential toxicity. Zinc accumulation may also be a useful indicator of zinc toxicity, but careful comparison with control or reference animals is necessary because of the small differences between toxic and control concentrations. Copper is not accumulated by H. azteca under chronic exposure conditions and body burdens of field animals cannot be used as an indicator of exposure or potential toxic effects. Short term exposures to copper, however, result in elevated copper concentrations in H. azteca, even at concentrations below those causing chronic toxicity. Short term bioaccumulation studies might, therefore, provide a useful indication of potential chronic copper toxicity.