Mosquito coil smoke inhalation toxicity. Part II: subchronic nose-only inhalation study in rats

This paper addresses the results of a subchronic inhalation study in rats exposed to the smoke of burning mosquito coils manufactured in Indonesia. The objective of the study was a comparative assessment of different mosquito coils, including a blank coil, utilizing the OECD No. 413 testing paradigm, however, with the focus on hazard identification at a single maximum tolerated exposure concentration rather than concentration-response. Groups of rats were nose-only exposed 6 h a day, 5 days a week for 13 weeks to an average particulate concentration of 30 mg m(-3) from either blank coils or coils that contain the insecticidal ingredient transfluthrin. Nose-only air-exposed rats served as a control. A range of markers of exposure have been characterized to define the most critical exposure metrics with regard to total suspended particulate matter (TSP) and potentially noxious volatile products of combustion. During the course of the exposure period the smoke-exposed rats showed clinical signs suggestive of acute upper respiratory tract sensory irritation. Body weights were mildly affected in the male rats, but food and water consumption were indistinguishable amongst the groups. Carboxyhemoglobin concentrations were approximately 11% throughout the exposure period in smoke exposed rats. Hematology, clinical pathology and urinalysis as well as the analysis of organ weights and histopathology of extrapulmonary organs and the lung did not reveal any evidence of adverse systemic or local effects, whereas in the anterior region of the nasal passages, and to some extent also in the larynx, irritant-related changes typical for water-soluble upper respiratory irritants were found. Markers of pulmonary inflammation or increased phagocytosis and lysosomal activity in bronchoalveolar lavage were indistinguishable amongst the groups. gamma-Glutamyltranspeptidase was significantly increased in the smoke exposure groups, which is taken as indirect evidence of an adaptive upregulation of the pulmonary antioxidant glutathione. In rats exposed to mosquito coil smoke containing transfluthrin, a somewhat increased frequency of alveolar macrophages with foamy appearance was identified through cytodifferentiation but not histopathology compared with the blank coil. From the specific staining of intracellular phospholipids, the notion is supported that this equivocal finding is probably related to an increased uptake of modified pulmonary surfactant rather than increased engulfment of insoluble particulate matter since pigmentation or clustering or intra-alveolar cells did not occur. The results of this subchronic inhalation study support the conclusion that smoke from burning mosquito coils in concentrations high enough to elicit acute upper respiratory tract irritation due to the presence of common wood-combustion products (such as aliphatic aldehydes) did not cause any adverse effect in the lower respiratory tract or any other extrapulmonary organ. The most critical mode of action is related to acute and readily perceivable sensory irritation. The concentration tested was estimated to be well above that occurring under more realistic exposure conditions. Therefore, overnight exposure to the smoke from burning mosquito coils (manufactured in Indonesia) is unlikely to be associated with any unreasonable health risk.