Household insecticides: evaluation and assessment of inhalation toxicity: a workshop summary.
Particularly in tropical countries household insecticides are used on a day-by-day basis to control mosquitoes, other crawling and flying insects to prevent the spread of vector-borne diseases. The products used most often are spray-cans, oil-sprays, mosquito coils as well as slow-release vaporising systems such as mats and liquid vaporiser. The extent and duration of exposure of humans is highly dependent on the type of product used. The objective of this workshop was to analyse the necessity and feasibility of inhalation studies with household insecticides taking into account the specific constrains associated with each type of end-use product. The standardisation of inhalation studies with regard to the generation of test atmospheres, mode and duration of exposure, and selection of adequate toxicological endpoints were addressed. Due to the complex nature of exposure atmospheres generated by some household insecticides, viz. mosquito coils, it is scientifically challenging to characterise the pathomechanism of most concern, since irritant combustion gases, volatile and semi-volatile organic substances, particulates (soot), condensation aerosols and re-condensed substances onto particulates may act independently, synergistically or mixture specific. It has been concluded that for the comparative safety evaluation and risk assessment of indoor insecticide end-use products generally recognised guidance for harmonised inhalation testing is required: 1) For high-dose release products, such as spray-cans, acute inhalation testing appears to be most relevant. 2) For low-dose, slow-release devices, subchronic inhalation studies of 13-weeks, duration of exposure 6 hours/day for 5 consecutive days per week, should be performed on rats preferably with the end-use product. A dose-range finding study of 2-weeks duration, daily exposure, should be available for the justification of dose selection and to demonstrate that the findings of 5 days/week exposure is not different from that utilising a daily exposure. 3) In certain instances, inhalation testing of shorter duration, for example 2 or 4 weeks, may be appropriate if the inhalation toxicity of the basic formula has already been characterised or the major constituents contained in the formulation have been examined in extant studies. The duration of study should also depend on actual use and exposure pattern, the accumulation potential and the mode of action of the ingredients of concern. 4) Particularly for mosquito coil smokes, the possible physico-chemical interactions of particulates, potentially irritant water soluble or nonsoluble vapours and aerosol or vapours of the active ingredient(s) are virtually impossible to predict without appropriate inhalation testing. 5) Physiological measurements may be useful for the detection and quantification of the respiratory tract sensory irritation potency. Biochemical endpoints in lung lavage and conventional histopathology of the lungs and extrathoracic airways are considered to be important. 6) It has been agreed that the nose-only exposure technique provides the most cost-effective and controlled means to expose small laboratory animals to well defined atmospheres as long as the limitations of this technique are taken into account.