Prenatal exposure to pesticide ingredient piperonyl butoxide and childhood cough in an urban cohort.

RATIONALE: Previously we reported that airborne concentrations of cis-permethrin, but not trans-permethrin, measured during pregnancy in an inner city pediatric cohort was associated with cough by age 5. However, the effect of subsequent exposures to both permethrins during early childhood, and to piperonyl butoxide (PBO, a synergist for residential pyrethroid insecticides) remains to be elucidated. We hypothesized that prenatal and age 5-6 year measures of PBO and permethrins would be associated with cough at age 5-6 years in this cohort. Further, we explored the associations between these pesticide measures and wheeze, asthma, seroatopy, and fractional exhaled nitric oxide (FeNO). METHODS: PBO and permethrins were measured in personal air during the third trimester of pregnancy and indoor residential air at age 5-6 years (n=224). Health outcome questionnaires were administered to the mothers of 5-6 year old children. Indoor allergen specific and total immunoglobulin (Ig) E production was measured from sera collected at age 5, and FeNO was measured at 5-6 years. The hypotheses were tested using regression models adjusting for common confounders. RESULTS: Noninfectious cough was reported among 14% of children at age 5-6 years. Measures of prenatal PBO, but not age 5-6 year PBO or permethrins, increased the odds of cough [OR (95% CI): 1.27 (1.09-1.48), p<0.01; n=217]. No significant associations were found for other measured health outcomes. CONCLUSIONS: Prenatal PBO exposure was associated with childhood cough. It is unclear whether the observed effect is due mainly to PBO itself or residential pyrethroids of which PBO is an indicator.

Plasma achiral and chiral pharmacokinetic behaviour of intravenous oxfendazole co-administered with piperonyl butoxide in sheep.

Co-administration of piperonyl butoxide (PB) potentiates fenbendazole (FBZ) in small ruminants. The resultant increase in bioavailability of FBZ and its metabolite oxfendazole (OFZ) has important implications for the efficacy of these drugs against benzimidazole (BZD)-resistant strains of Teladorsagia circumcincta. This study evaluated the racemic (achiral) and enantiomeric (chiral) plasma disposition kinetics of OFZ and its metabolites after the co-administration of PB and OFZ in sheep. Six 6-8-month-old, parasite-free, female Dorset sheep (30-40 kg) were used in a two-phase crossover experiment. In phase I, three sheep received 30 mg/kg PB orally, followed by a single intravenous (i.v.) injection of OFZ at 5 mg/kg. The other three animals were treated similarly except that 5 mL of water replaced PB. In phase 2, treatments for the two groups were reversed and were given 14 days after the initiation of phase I. Three analytes OFZ, FBZ and fenbendazole sulphone (FBZSO(2)) were recovered in plasma up to 48 h post-treatment in both experimental groups. Achiral and chiral pharmacokinetic (PK) profiles for OFZ, after the co-administration of PB, were characterized by a significantly greater area under the concentration--time curve (AUC) and a longer mean residence time (MRT). Chiral OFZ distribution ratios were comparable in both treatment groups. Piperonyl butoxide treatment markedly influenced the plasma PK profiles for FBZ and FBZSO(2) following OFZ administration. Production of FBZ was enhanced as reflected by increased (> 60%) AUC, delayed T(max) and a significantly delayed (> 45%) elimination (t(1/2)(el)). Although AUC values for FBZSO(2) were not significantly different between groups, this metabolite was depleted more slowly from plasma (t(1/2)(el) > 60% and MRT > 42%) following PB treatment. This study demonstrated that PB co-administration is associated with an inhibition of OFZ biotransformation, as evidenced by the significantly higher plasma concentrations of OFZ and FBZ, and this could have important implications in terms of anti-parasite therapy against BZD-resistant parasite strains.

Determination of traces of pyrethrins and piperonyl butoxide in biological material by high-performance liquid chromatography.

A liquid chromatographic method for the determination of pyrethrins and of the synergist piperonyl butoxide in human plasma after C18 solid-phase extraction is described. UV detection was found to be sensitive enough to determine concentrations far below the limit of toxicity. With respect to future investigations concerning studies in biological materials, a column-switching system for sample preparation was developed and compared with solid-phase extraction. Both methods show comparable limits of detection, but the column-switching technique has the advantage of fully automating the system.