Acute pulmonary Toxicity/ Pathogenicity test for the evaluation of MPCA (Microbial Pest Control Agents). EPA-OPPTS 885. 3150: 1996 - Acute pulmonary toxicity, pathogenicity evaluation.
Test accredited by ENAC (Spanish National Accreditation Entity).
Test with the Certificate of Good Laboratory Practices (GLPs).
The results obtained with the pulmonary toxicity/pathogenicity studies following this guideline, provide information on the health risks that can be derived after a single respiratory (intranasal or intratracheal) exposure of an MPCA (Microbial Pest Control Agent) product intended for pest control, using a single high dose in a test with experimental animals, and carrying out post-exposure monitoring.
The MPCA product can contain any type of infectious agent (bacteria, fungi, parasites or viruses). The MPCA agent evaluated must be quantified by the appropriate microbiological methods according to the type of agent, so the manufacturer must report the microbial content of the product and its quantification per unit volume or weight of the product since the method requires a dose of 108 MPCA units to each animal. The MPCA product must have an aerodynamic average diameter that allows its penetration by respiratory route (intranasal instillation or intratracheal inoculation), and if this is not possible, the isolated forms of the agents it contains should be tested. Therefore, the manufacturer must report the size of the particles that make up the MPCA product.
The recommended animals are rodents (mice or rats) young adults of both sexes, of similar weight, although with justification other types of animals can be used (in IVAMI we use mice). The inoculated animals should be evaluated with a daily follow-up from the beginning of the inoculation until a later period of 21 days (unless it should be prolonged or shortened by persisting the signs of toxicity and pathogenicity, or animals die, respectively). The clinical monitoring to observe the corporal and behavioral manifestations of the animals must be complemented with the pathological examination of a part of the inoculated animals (6 animals) three days after the administration of the product, and later on a weekly basis, after the administration (4 evaluations with internal organs study of 6 animals in each of them). In addition, a control group inoculated with the same inactivated MPCA product must be included and subjected to the same type of monitoring. If the toxicity of the vehicle (excipient) of the MPCA product is not known, another toxicity control group of the vehicle (excipient) of the product must be included, so the manufacturer/promoter of the test must inform about it. Periodic and final follow-up, in addition to the observations to detect clinical manifestations, will include the weighing of the animals, the macroscopic examination of internal organs and detection/quantification of the MPCA agent in the lungs, liver, brain, kidneys, spleen, lymph nodes, blood and cecal content. The aim of the qualitative and quantitative microbiological evaluation is to evaluate the organic dissemination and the clearance, where appropriate, of the MPCA agent.