Derivation and application of indoor air screening values for inhalation exposure to semi-volatile organic compounds.

Semi-volatile organic compounds (SVOCs) are being increasingly studied in indoor air. The absence of health-based inhalation exposure guidelines for most SVOCs impedes the interpretation of indoor air concentrations from a health risk context. To accelerate the derivation of screening values for a large number of SVOCs, a tiered framework was developed to evaluate and adjust published hazard assessments for SVOCs to calculate benchmarks relevant for evaluation of inhalation risk. Inhalation screening values were derived for 43 SVOCs considered in this study, most of which required extrapolation from oral exposure guidelines. The screening values were compared to published SVOC concentrations in homes in Canada to evaluate the potential health risks of chronic exposure to SVOCs in indoor residential environments. SVOCs that could be prioritized for further evaluation were dibutyl phthalates (DBP), di(2-ethylhexyl) phthalate (DEHP) and polybrominated diphenyl ethers (PBDEs). The framework could be applied more broadly in the future to derive screening values for other non-traditional indoor air contaminants with limited inhalation hazard data or assessments.

Estimation of multi-route exposures to various chemicals during Children's clay toy use.

Clay toys have been used as play materials and educational tools for children. Clay toys exhibit adherent properties, and may facilitate chemical ingestion via dermal absorption and oral (hand-to-mouth, HTM) exposures. Inhalation exposure also be considered when contain volatile chemicals. The purpose of this study was to estimate the exposure dose for chemicals in clay toys via three exposure routes, and to evaluate the relationship between the exposure contribution of each route considering both the chemical properties and children's age. Chemical analysis was conducted for 9 semi-volatile organic compounds (SVOCs), 17 volatile organic compounds (VOCs), and 7 metal elements in clay toys (n = 66) purchased from Korean market. Exposure factors for usage pattern of clay toys were conducted based on a nationally representative survey in Korea. A total of 12,144 (60.7%) children responded positively to playing with clay toys. Exposure to SVOCs and VOCs in clay toys via HTM, inhalation, and dermal absorption were estimated. The exposure level was the highest in styrene with 5.2 × 10-3 mg/kg-bw/day (95th percentile population), which was approximately 13% of the acceptable daily dose for styrene. In 3-year-old children, dermal absorption route contributed the highest at 59.2-100%. Chemicals with higher octanol-water partition coefficient (Kow) had the greater the contribution of the dermal absorption route and the weaker the contribution of the HTM route. In infants (0-2 years), the contribution via HTM exposure was higher than that in the other age groups. The contribution of inhalation exposure differed depending on the volatility of the chemicals. Furthermore, the exposure route contribution significantly differed due to age-dependent behavioral changes in children. These results suggest that the exposure assessments for children could be considered with multiple exposure routes related to chemical properties.

Strategies for overcoming the biological barriers associated with the administration of inhaled monoclonal antibodies for lung diseases.

INTRODUCTION: Monoclonal antibodies (mAbs) should be administered by inhalation rather than parenterally to improve their efficiency in lung diseases. However, the pulmonary administration of mAbs in terms of aerosol technology and the formulation for inhalation is difficult. AREAS COVERED: The feasible or suitable strategies for overcoming the barriers associated with administering mAbs are described. EXPERT OPINION: Providing mAbs via inhalation to individuals with lung disorders is still difficult. However, inhalation is a desirable method for mAb delivery. Inhaled mAb production needs to be well thought out. The illness, the patient group(s), the therapeutic molecule selected, its interaction with the biological barriers in the lungs, the formulation, excipients, and administration systems must all be thoroughly investigated. Therefore, to create inhaled mAbs that are stable and efficacious, it will be essential to thoroughly examine the problems linked to instability and protein aggregation. More excipients will also need to be manufactured, expanding the range of formulation design choices. Another crucial requirement is for novel carriers for topical delivery to the lungs since carriers might significantly enhance proteins' stability and pharmacokinetic profile.

Assessment of Drug Usage Pattern among Bronchial Asthma Patients in a Tertiary Care Teaching Hospital, Tamilnadu: A Cross-sectional Study.

BACKGROUND: Asthma is a chronic inflammatory disease of the small airways. Chronic inflammation often causes hyper responsiveness of airways with wheezing, breathing difficulty, cough and chest tightness. OBJECTIVE: The present study aimed to evaluate the drug usage pattern of anti-asthma drugs among asthma patients. METHODS: The present study was a prospective, observational cross-sectional study carried out among 422 outpatients being treated at the respiratory medicine department, SRM Medical College Hospital and Research Centre. Data regarding the prescribing indicators and patient indicators were collected from the patients' prescription slips and entered in the preformed proforma. Prescribing indicators were taken into consideration in evaluating the rationality of prescriptions. RESULTS: In the present study, 49% of patients were between the age group of 20-40 years. Genderwise distribution showed 58.05% of males and 41.95% of females. A family history of asthma was seen in 68% of the study population. The present study reported smoking among 51% and tobacco chewing in 21% of the study population. Low economic strata were observed in 77.9% of the study population. According to asthma grading, 65.8% were in the mild intermittent, and 25% were in the mild persistent group. Patients were on ß2 agonists (35.4%) and corticosteroids (32%). The most commonly used fixed drug combination was a short-acting ß2 agonist with corticosteroid (40.5%). A total of 68% of drugs were used by the inhalational route and 29% by the oral route. CONCLUSION: The findings showed that, the most frequently prescribed drug was a short-acting ß2 agonist with corticosteroid in a fixed-dose combination via inhalational route.

Therapeutic Use of an Inhaled Drug Delivery in Pulmonary Hypertension: A Review.

Pulmonary arterial hypertension (PAH) is a serious condition in which there is increased blood pressure in arteries of the lungs (pulmonary arteries). The therapies or drugs for PAH have expanded with the revelation of three key pathological processes - encompassing prostacyclin, nitric oxide (NO), and endothelin pathways. An outlook for patients suffering from PAH is still mediocre amidst recent advancements. The evolution of pre-clinical and clinical research on PAH has facilitated the identification of several new targeted therapies for the disease. In this article, we examine recent data on new pulmonary hypertension physiological pathways, primarily concentrating on administering drugs through the inhalation route and their effects. Although they have been given clinical use approval, medications based on these routes are presently being studied in clinical or pre-clinical settings. To confirm these innovative medicines' therapeutic efficacy and safety, extensive clinical trials are needed.

The future of inhalation therapy in chronic obstructive pulmonary disease.

The inhaled route is critical for the administration of drugs to treat patients suffering from COPD, but there is still an unmet need for new and innovative inhalers to address some limitations of existing products that do not make them suitable for many COPD patients. The treatment of COPD, currently limited to the use of bronchodilators, corticosteroids, and antibiotics, requires a significant expansion of the therapeutic armamentarium that is closely linked to the widening of knowledge on the pathogenesis and evolution of COPD. The great interest in the development of new drugs that may be able to interfere in the natural history of the disease is leading to the synthesis of numerous new molecules, of which however only a few have entered the stages of clinical development. On the other hand, further improvement of inhaled drug delivery could be an interesting possibility because it targets the organ of interest directly, requires significantly less drug to exert the pharmacological effect and, by lowering the amount of drug needed, reduces the cost of therapy. Unfortunately, however, the development of new inhaled drugs for use in COPD is currently too slow.

Preclinical Characterization of Antinociceptive Effect of Bergamot Essential Oil and of Its Fractions for Rational Translation in Complementary Therapy.

Bergamot essential oil (BEO) is endowed with consistent and reproducible antinociceptive and anti-allodynic properties when administered via an inhalation route. However, the effects of its main constituents and of its decolored (DEC) and deterpenated (DET) fractions, which are enriched in limonene or in linalool and linalyl acetate, respectively, on spontaneous motor activity related to anxiety and on formalin-induced licking/biting biphasic behavior have never been investigated before. Therefore, the present research aims to characterize the role of BEO components on an experimental pain model that is relevant to clinical translation. Under our present experimental conditions, a paper filter disc soaked with different volumes of the phytocomplex and of its fractions that was applied at the edge of the observation chamber allowed the effects on the spontaneous motor activity and on the formalin-induced nocifensive response in ddY-strain mice to be studied. The present research demonstrated the effects of the DEC fraction of BEO on motor activity and on formalin-induced licking/biting behavior for the first time, proving that limonene is implicated in reduced motor activity and that it is important for the analgesic effect.

Pharmacokinetic/pharmacodynamic approaches to drug delivery design for inhalation drugs.

Introduction: Inhaled drugs are important in the treatment of many lung pathologies, but to be therapeutically effective they must reach unbound concentrations at their effect site in the lung that are adequate to interact with their pharmacodynamic properties (PD) and exert the pharmacological action over an appropriate dosing interval. Therefore, the evaluation of pharmacokinetic (PK)/PD relationship is critical to predict their possible therapeutic effect.Areas covered: We review the approaches used to assess the PK/PD relationship of the major classes of inhaled drugs that are prescribed to treat pulmonary pathologies.Expert opinion: There are still great difficulties in producing data on lung concentrations of inhaled drugs and interpreting them as to their ability to induce the desired therapeutic action. The structural complexity of the lungs, the multiplicity of processes involved simultaneously and the physical interactions between the lungs and drug make any PK/PD approach to drug delivery design for inhalation medications extremely challenging. New approaches/methods are increasing our understanding about what happens to inhaled drugs, but they are still not ready for regulatory purposes. Therefore, we must still rely on plasma concentrations based on the axiom that they reflect both the extent and the pattern of deposition within the lungs.

Comparison of PBTK model and biomarker based estimates of the internal dosimetry of acrylamide.

Estimates of internal dosimetry for acrylamide (AA, 2-propenamide; CASRN: 79-06-1) and its active metabolite glycidamide (GA) were compared using either biomarkers of internal exposure (hemoglobin adduct levels in rats and humans) or a PBTK model (Sweeney et al., 2010). The resulting impact on the human equivalent dose (HED, oral exposures), the human equivalent concentration (HEC, inhalation), and final reference values was also evaluated. Both approaches yielded similar AA HEDs and HECs for the most sensitive noncancer effect of neurotoxicity, identical oral reference doses (RfD) of 2×10(-3) mg AA/kg bw/d, and nearly identical inhalation reference concentrations (RfC=0.006 mg/m(3) and 0.007 mg/m(3), biomarker and PBTK results, respectively). HED and HEC values for carcinogenic potential were very similar, resulting in identical inhalation unit risks of 0.1/(mg AA/m(3)), and nearly identical oral cancer slope factors (0.4 and 0.5/mg AA/kg bw/d), biomarker and PBTK results, respectively. The concordance in estimated HEDs, HECs, and reference values from these two diverse methods increases confidence in those values. Advantages and specific application of each approach are discussed. (Note: Reference values derived with the PBPK model were part of this research, and do not replace values currently posted on IRIS: http://www.epa.gov/iris/toxreviews/0286tr.pdf.).