Acute oral toxicity/pathogenicity test for the evaluation of MPCA (Microbial Pest Control Agents) products. EPA-OPPTS 885. 3050: 1996 - Acute Oral Toxicity/Pathogenicity.
Test with the Certificate of Good Laboratory Practices (GLPs).
The results obtained with the oral toxicity/pathogenicity studies following this standard provide information on the health hazards that may arise after a single oral exposure of a MPCA (Microbial Pest Control Agent) product intended for pest control, using a single high dose in a test with experimental animals, and with post-exposure monitoring. If the test substance cannot be administered in a single exposure, it should be distributed in small doses over 24 hours.
The MPCA product can contain any type of infectious agent (bacteria, fungi, parasites or viruses). The evaluated MPCA agent 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 of volume or weight of the product since the method requires administering a dose of 108 MPCA units to each animal.
The recommended animals are rodents (mice or rats) young adults of both sexes, of similar weight, although other types of animals may be used with justification. Inoculated animals should be evaluated with daily follow-up from the start of inoculation to a subsequent period of 21 days (unless it must be prolonged or shortened due to persisting signs of toxicity and pathogenicity, or the animals die, respectively). The clinical follow-up to observe the corporal and behavioral manifestations of the animals should be complemented with the pathological examination of a part of the inoculated animals (6 animals) three days after the administration of the product, and subsequently weekly, after the administration. (4 evaluations at days 3, 7, 14 and 21, with study of internal organs of 6 animals in each of them). In addition, a non-inoculated control group must be included and will be subjected to the same type of follow-up. In case 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 trial must report this. A third control group can be included with the inactivated product. The 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 the detection/quantification of the MPCA agent in the lungs, liver, brain, kidneys, spleen, lymph nodes, blood and cecal content. The objective of the qualitative and quantitative microbiological evaluation is to evaluate the organic spread and clearance, if applicable, of the MPCA agent.
Information required from the manufacturer/developer
For the above reasons, the manufacturer/promoter of the MPCA trial must report the type of presentation of the MPCA product; the size of the particles if they are solid or are suspended in a liquid; of the agent (microorganism) included in the product and in the case of fungi if it contains conidia (spores) or also mycelial hyphae; its quantification per unit of weight or volume; and knowledge, if any, of the toxicity of the vehicle (excipient). With the information provided, the laboratory will be able to evaluate the total number of animals necessary to carry out the study, as well as the microbiological methods necessary for its evaluation. In addition to the required untreated control group, the EPA guide includes two additional control groups: a vehicle (excipient) control group (only required when vehicle toxicity is unknown) and a control group administered the inactivated MPCA product (necessary when the final product is tested to evaluate the toxic properties of MPCA). Depending on the product under test, the study should be performed with the indicated controls. An additional 20 animals should be used for each of the chosen control groups.