Kit de Herramientas para el Registro de Plaguicidas

#642 Toxicological and Exposure Data of MPCA

Objective of the study

Microorganisms developed for biocontrol purposes generally represent a low risk to humans. However, data or reasoned cases must be provided which satisfactorily explain the pathogenic potential, their ability to infect the test animal, and pattern of clearance. Any information on health and safety from the use and production of the Microbial Pest Control Active (MPCA) and from good quality literature is also provided.

Circumstances under which the study is recommended to be required

Always required.

Principles about reasoned cases for non-provision of studies

This requirement can have a reasoned case for non-provision of studies. For example, if there is good data provided for the strain that demonstrates that it is unable to grow at human body temperatures, then a case can be made for absence of pathogenicity. Or if metabolites are demonstrated to be absent then toxicity can be excluded.

Test organism or substrate

The entire MPCA.

Typical information to be provided by the applicant

Information provided for pathogenicity and toxicity usefully includes details about the health effects of the MPCA, using good quality studies and literature. If the microorganism produces toxicologically relevant secondary compounds (metabolites), then results from studies or literature on the human health effects expected from that secondary compounds (metabolites) can usefully be included.

  1. Acute toxicity (single exposure toxicity/pathogenicity) studies.
  2. Higher tier studies.
  3. Genotoxicity is required if relevant secondary compounds (metabolites) are present.
  4. Reports of adverse effects of the MPCA.

Ref 1: Basic studies, using protocols adapted for microorganisms, should include infectivity and pathogenicity and toxicity from oral and intratracheal routes. In some cases, it may be possible to present a reasoned case for non-provision of study data. The only microorganism adapted test methods are those developed by the USA EPA, these OPPTS guidelines for microbial active substances maintain that a single dose level of at least 108 CFU/test animal should be used for oral and intratracheal studies, and a 107 for injection studies. Often, this level is not possible for administration with MPCA, and a justification for a lower dose is required. Microbials can also have an issue with meeting the conditions for validity for pulmonary testing; in this case, an explanation with accompanying lab data is submitted.

Ref. 2: For the MPCA repeat dose, sub-chronic or chronic studies are not usually necessary. However, if adverse effects are noted in the acute studies these may need to be further investigated. When relevant secondary compounds (metabolites) are confirmed to be present are toxic, additional studies may be considered.
Ref. 4 Data should be provided of records of any reported incidence of adverse effects in literature and any studies done to establish that the MPCA does not cause unacceptable adverse effects for humans.Ref. 4: Occupational health and safety reports from the production facility are considered useful.

Typical endpoints of the study

Typically, endpoints will be the amount of cfu/kg body weight for an effect to be observed. Often, no significant adverse effects are observed even at the highest rate, leaving the official endpoint to be represented above the tested dose or concentration, according to the test method used.

Testing guidelines

There is no single guideline appropriate for use for MPCA. The applicant will use either one of the guidelines below or a combination, with adjustments suited for the test product. The information will also be from good quality literature, company statements, plus some experimental reports. Due to the commitment to reduce vertebrate testing, it is encouraged to allow alternative test methods if valid.