Dose-dependent difference of nuclear receptors involved in murine liver hypertrophy by piperonyl butoxide.

Nuclear receptors play important roles in chemically induced liver hypertrophy in rodents. To clarify the involvement of constitutive androstane receptor (CAR) and other nuclear receptors in mouse liver hypertrophy induced by different doses of piperonyl butoxide (PBO), wild-type and CAR-knockout mice were administered PBO (200, 1,000, or 5,000 ppm) in the basal diet for 1 week. Increased liver weight and diffuse hepatocellular hypertrophy were observed at 5,000 ppm for both genotypes, accompanied by increased Cyp3a11 mRNA and CYP3A protein expression, suggesting that CAR-independent pathway, possibly pregnane X receptor (PXR), plays a major role in the induction of hypertrophy. Moreover, wild-type mice at 5,000 ppm showed enhanced hepatocellular hypertrophy and strong positive staining for CYP2B in the centrilobular area, suggesting the localized contribution of CAR. At 1,000 ppm, only wild-type mice showed liver weight increase and centrilobular hepatocellular hypertrophy concurrent with elevated Cyp2b10 mRNA expression and strong CYP2B staining, indicating that CAR was essential at 1,000 ppm. We concluded that high-dose PBO induced hypertrophy via CAR and another pathway, while lower dose of PBO induced a pathway mediated predominantly by CAR. The dose-responsiveness on liver hypertrophy is important for understanding the involvement of nuclear receptors.

Effects of pyperonyl butoxide on the female reproductive tract in rats.

This study was investigated the effects of piperonyl butoxide (PBO) on the female reproductive tract. Female Crj:Donryu rats were fed a basal diet containing 5,000, 10,000 or 20,000 ppm PBO for 28 days, and compared with food-restricted rats of comparable body weights to those in the PBO 10,000 or 20,000 ppm groups. Although treatment with 20,000 ppm PBO for 28 days depressed body weight gain, the abnormal estrous cyclicity, mainly prolonged diestrus, was also induced by the PBO treatment which was not correlated with body weight change. 20,000 ppm PBO treatment markedly decreased uterine weights and slightly decreased ovarian weights. 10,000 and 20,000 ppm PBO treatment increased liver weights. These cycle and organ weight changes were linked to atrophic uterus and increased atretic follicles in the ovary. In hormone assays, PBO at both doses reduced serum E2 levels, but did not affect corticosterone levels. An anti-uterotrophic assay showed a slight but significant decrease in absolute uterine weight and a reduction of endometrial epithelium height in the 20,000 ppm group. PBO was positive in an ER α antagonist reporter gene assay, although the activity was much weaker than that of 4-hydroxytamoxifen. These results indicate that high-dose PBO treatment directly induces atrophic changes in the female reproductive tract in rats, and these effects are likely the result of a hypoestrogenic state and the anti-estrogenic activity of PBO.

Impact of prenatal exposure to piperonyl butoxide and permethrin on 36-month neurodevelopment.

OBJECTIVE: Recent pesticide-monitoring results suggest that a shift in residential pesticide exposure from organophosphorus insecticides to pyrethroid insecticides has occurred. Pyrethroid insecticides are potential neurodevelopmental toxicants and have not been evaluated for developmental toxicity. Our objective was to explore the association between prenatal exposure to permethrin (a common pyrethroid) and piperonyl butoxide (a pyrethroid synergist) and 36-month neurodevelopment. METHODS: Participants is this study were part of a prospective cohort of black and Dominican mothers and newborns living in low-income neighborhoods in New York City. We examined 36-month cognitive and motor development (using the Bayley Scales of Infant Development, second edition) as a function of permethrin levels measured in maternal and umbilical cord plasma collected on delivery and permethrin and piperonyl butoxide levels measured in personal air collected during pregnancy. All models were controlled for gender, gestational age, ethnicity, maternal education, maternal intelligence, quality of the home environment, and prenatal exposure to environmental tobacco smoke and chlorpyrifos. RESULTS: Prenatal exposure to permethrin in personal air and/or plasma was not associated with performance scores for the Bayley Mental Developmental Index or the Psychomotor Developmental Index. After data adjustment, children more highly exposed to piperonyl butoxide in personal air samples (>4.34 ng/m(3)) scored 3.9 points lower on the Mental Developmental Index than those with lower exposures (95% confidence interval: -0.25 to -7.49). CONCLUSIONS: Prenatal exposure to piperonyl butoxide was negatively associated with 36-month neurodevelopment.

A randomised, assessor blind, parallel group comparative efficacy trial of three products for the treatment of head lice in children--melaleuca oil and lavender oil, pyrethrins and piperonyl butoxide, and a "suffocation" product.

BACKGROUND: There are many different types of pediculicides available OTC in Australia. In this study we compare the efficacy and safety of three topical pediculicides: a pediculicide containing melaleuca oil (tea tree oil) and lavender oil (TTO/LO); a head lice "suffocation" product; and a product containing pyrethrins and piperonyl butoxide (P/PB). METHOD: This study was a randomised, assessor-blind, comparative, parallel study of 123 subjects with live head lice. The head lice products were applied according to the manufacturer's instructions (the TTO/LO product and the "suffocation" product were applied three times at weekly intervals according to manufacturers instructions (on Day 0, Day 7 and Day 14) and the P/PB product was applied twice according to manufacturers instructions (on Day 0 and Day 7)). The presence or absence of live lice one day following the last treatment was determined. RESULTS: The percentage of subjects who were louse-free one day after the last treatment with the product containing tea tree oil and lavender oil (41/42; 97.6%) and the head lice "suffocation" product (40/41, 97.6%) was significantly higher compared to the percentage of subjects who were louse-free one day after the last treatment with the product containing pyrethrins and piperonyl butoxide (10/40, 25.0%; adj. p < 0.0001). CONCLUSION: The high efficacy of the TTO/LO product and the head lice "suffocation" product offers an alternative to the pyrethrins-based product. TRIAL REGISTRATION: The study was entered into the Australian/New Zealand Clinical Trial Registry, ACTRN12610000179033.

Human exposure to insecticide products containing pyrethrins and piperonyl butoxide (2001-2003).

Pyrethrum, used as an insecticide for centuries, is derived from dried and ground flowers of Chrysanthemum cinerariaefolium. Its current major use is in insecticide products to the control insects in the home and food handling establishments. We investigated human incidents reported through the American Association of Poison Control Centers (AAPCC) Toxic Exposure Surveillance System (TESS) associated with regulated insecticides containing pyrethrins and piperonyl butoxide (PY/PBO) from 2001 to 2003. Special attention was paid to dermal and respiratory effects. Although there are limitations associated with TESS data, we observed that In view of their widespread use, the data indicates that PY/PBO products can be used with a relatively low risk of adverse effects. Moreover, the data suggest that they are not likely to cause reactions in people with asthma or allergies.

North American efficacy and safety of a novel pediculicide rinse, isopropyl myristate 50% (Resultz).

BACKGROUND: Head lice infestations are a major nuisance in school-aged children and are a worldwide public health problem. There are growing concerns about the effectiveness of current treatments owing to increasing resistance, safety, and patient noncompliance. A safe, easy to use, effective alternative is needed. OBJECTIVE: A pediculicide rinse, 50% isopropyl myristate (IPM), was assessed in two phase 2 trials conducted in North America. The first trial was a nonrandomized (proof of concept) trial without a comparator conducted in Winnipeg, Canada. The second trial, conducted in the United States, was an evaluator-blinded, randomized superiority trial comparing 50% IPM rinse with a positive control (RID; pyrethrin 0.33%, piperonyl butoxide 4%). The primary end points were to determine the safety and efficacy of 50% IPM as a pediculicide rinse. METHODS: Subjects meeting inclusion criteria were enrolled in the above-mentioned trials with efficacy end points 7 and 14 days post-treatment. Subjects were also evaluated on days 0, 7, 14, and 21 for the presence of erythema and edema using the Modified Draize Scale. Other comments associated with the safety evaluation (ie, pruritus) were collected. RESULTS: IPM was found to be effective in the proof of concept study and comparator trial using a positive control. IPM was also well tolerated, with minimal adverse events. All adverse events were mild, resolving by completion of the study. CONCLUSION: Data suggest that IPM is a safe and effective therapy for the treatment of head lice in children and adults. IPM's mechanical mechanism of action makes development of lice resistance unlikely.

Intoxicación por piretrinas: una causa singular de convulsiones en el lactante / Intoxication from pyrethrins: a singular cause of seizures in the infant

Las piretrinas naturales y los piretroides sintéticos soninsecticidas que se encuentran en varios productos comerciales, destinados a la erradicación de insectos en establecimientos públicos y en hogares. Aunque se consideran poco tóxicos, la exposición a estos productos puede causar en humanos trastornos cutáneos, respiratorios, gastrointestinales y, excepcionalmente, neurológicos. La información relativa a los efectos de estas sustancias en niños es muy escasa. Se describeel caso de un niño de cinco meses con convulsiones,en el que la exposición a un insecticida y los estudios complementarios han permitido establecer el diagnóstico de intoxicación por piretrinas como causa más probable del cuadro clínico. Su interés radica en destacar la presentación clínica poco habitual y la baja frecuencia con que se diagnostica este tipo de intoxicaciones. Se refieren también las formas clínicas de intoxicación por piretrinas y piretroides y su tratamiento, subrayando la dificultad del diagnóstico

Pathological laughter.

A man experienced one hour and 40 minutes of continual, inappropriate, uncontrollable laughter. The onset was preceded by a single-inhalation exposure to an insecticide of very low toxicity. The episode was terminated by a single dose of IV diazepam. A discussion of pathological laughter, including its proposed pathophysiology, differential diagnosis, clinical relevance, and management, is presented.

Anticonvulsant activity and neurotoxicity of piperonyl butoxide in mice.

Piperonyl butoxide, a microsomal monooxygenase inhibitor, administered intraperitoneally to mice exerts peak anti-maximal electroshock activity and peak neurotoxicity at 5 and 7h, respectively. The median neurotoxic dose is 1,690 mg/kg. In the maximal electroshock seizure test, the median effective dose (ED50) is 457 mg/kg and the protective index (PI) is 3.69. In the subcutaneous pentylenetetrazol test, the ED50 is 443 mg/kg and the PI is 3.81. Piperonyl butoxide prevents seizure spread and elevates seizure threshold. Its PI compares favorably with PIs of clinically useful anticonvulsants.