ABSTRACT
Piperonyl butoxide (PBO) is a popular insecticide synergist present in thousands of commercial, agricultural, and household products. PBO inhibits cytochrome P450 activity, impairing the ability of insects to detoxify insecticides. PBO was recently discovered to also inhibit Sonic hedgehog signaling, a pathway required for embryonic development, and rodent studies have demonstrated the potential for in utero PBO exposure to cause structural malformations of the brain, face, and limbs, or more subtle neurodevelopmental abnormalities. The current understanding of the pharmacokinetics of PBO in mice is limited, particularly with respect to dosing paradigms associated with developmental toxicity. To establish a pharmacokinetic (PK) model for oral exposure, PBO was administered to female C57BL/6J mice acutely by oral gavage (22-1800 mg/kg) or via diet (0.09 % PBO in chow). Serum and adipose samples were collected, and PBO concentrations were determined by HPLC-MS/MS. The serum concentrations of PBO were best fit by a linear one-compartment model. PBO concentrations in visceral adipose tissue greatly exceeded those in serum. PBO concentrations in both serum and adipose tissue decreased quickly after cessation of dietary exposure. The elimination half-life of PBO in the mouse after gavage dosing was 6.5 h (90 % CI 4.7-9.5 h), and systemic oral clearance was 83.3 ± 20.5 mL/h. The bioavailability of PBO in chow was 41 % that of PBO delivered in olive oil by gavage. Establishment of this PK model provides a foundation for relating PBO concentrations that cause developmental toxicity in the rodent models to Sonic hedgehog signaling pathway inhibition.
ABSTRACT
Purpose The purpose of this scoping review was to identify current measures used to evaluate the language abilities of multilingual preschoolers within the framework of the International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY; World Health Organization, 2007 ). Method This review adhered to established models for conducting a comprehensive, iterative scoping review outlined by Arksey and O'Malley (2005) and Levac, Colquhoun, and O'Brien (2010) and included the following phases: (a) articulating the research question; (b) identifying relevant studies; (c) selecting studies; (d) charting the data; and (e) collating, summarizing, and reporting the results. The ICF-CY was used to frame the identified measures ( World Health Organization, 2007 ). Results Three hundred twenty-five peer-reviewed publications were identified and included in this review. The majority of publications used measures that evaluated the activity component of multilingual preschoolers' language (70%), with few evaluating participation (9%). Most identified measures (73%) assessed children's semantic language skills. We also observed that 88% of studies explicitly measured children's language input to interpret assessment results. Conclusions A variety of measures are currently used that address the activity component of the ICF-CY with a particular emphasis on semantics. There is, however, a dearth of measures examining language abilities for participation. The authors strongly recommend an increased focus on the development, use, and evaluation of measures that explicitly assess multilingual preschoolers' language participation, particularly in school-based settings. Supplemental Material https://doi.org/10.23641/asha.8637206.
