The chlorophenoxy herbicide MCPA: a mechanistic basis for the observed differences in toxicological profile in humans and rats versus dogs.

Metabolism data for MCPA in rat, dog and human shows a single oral dose is quantitatively and rapidly absorbed with evidence of non-linear kinetics at >100 mg/kg bw. The extent of metabolism is low and consistent between rat and human, with substantially higher metabolic conversion in dog. Parent accounts for 50%-67% dose in rat, ∼40% in human and 2%-27% in dog. No dog specific metabolite is apparent.In rat and human, MCPA and metabolites are rapidly eliminated in urine (65%-70% within 24 h) but in dog, excretion is via urine and faeces (20%-30% within 24 h), with renal excretion saturating between 5 and 100 mg/kg bw.The species difference in excretion is reflected in pharmacokinetics. Terminal half-life is similar in rat and human (15-17 h) but higher in dog (47 h). Modelling shows species differences in single dose kinetics profoundly affect systemic exposure following repeat dosing.The difference in renal excretion and systemic exposure of MCPA between dogs and rats has been attributed to species differences in active transporters (OAT1/OAT3). A new in vitro flux study in renal proximal tubules supports this hypothesis with net secretion in rat and human of a similar magnitude but significantly less in dog.

Emergent Literacy Assessment in Children With Autism Spectrum Disorder Who Have Limited Verbal Communication Skills: A Tutorial.

Purpose Children with autism spectrum disorder (ASD) are at increased risk of experiencing difficulties with the development of literacy, including the emergent literacy skills recognized to underpin conventional literacy success. Comprehensive assessment is essential. Characteristics of ASD can make assessment challenging, and this can be compounded when children are unable to demonstrate their skills using spoken language. The purpose of this clinical tutorial is to outline the process of emergent literacy assessment for children with ASD who have limited verbal communication skills. A case example of a 5-year-old boy is presented. Method Pertinent literature is reviewed around the literacy profiles of children with ASD, the subgroup of children with ASD who have limited verbal communication skills, key components of emergent literacy, and previous research examining the emergent literacy abilities of children with ASD. The case report is described in depth and emphasizes the key factors to consider when designing an assessment battery and protocol. Results The case example information is interpreted, and its application is discussed. Key outcomes are highlighted including a greater understanding of the child's literacy strengths and needs and the implications for individualized instruction. Conclusion The clinical tutorial highlights the need for a comprehensive, well-planned assessment approach that involves all members of the educational team, and that is considerate to the needs of the individual child and responsive to their communication needs.

Genotoxicity assessment of the flavouring agent, perillaldehyde.

Perillaldehyde, a natural monocyclic terpenoid found most abundantly in the herb perilla, has a long history of use as a flavouring ingredient to add spiciness and citrus taste to foods. Previously, it was judged to be safe by several international expert panels. To confirm the safety of flavourings placed on the European Union list of flavourings, perillaldehyde was selected by the European Food Safety Authority as a representative of a subgroup of alicyclic aldehyde flavouring substances to be evaluated for genotoxic potential. Perillaldehyde was tested in a bacterial reverse mutation assay, an in vitro micronucleus assay in human lymphocytes, an HPRT assay in mouse lymphoma cells, and a micronucleus/comet assay in Han Wistar rats. In contrast to previously published results, perillaldehyde induced mutation in Salmonella typhimurium strain TA98 in the absence of metabolic activation. The comet assay was negative for duodenum and weakly positive for liver but only at a hepatotoxic dose of perillaldehyde. All other genotoxicity assays were negative. These data do not provide an indication of any genotoxic potential for perillaldehyde, and they provide the primary basis for recent scientific opinions regarding perillaldehyde genotoxicity announced by several international organizations responsible for safety assessment of food additives and flavourings.