Assessing Risks of Plant-Based Pharmaceuticals: II. Non-Target Organism Exposure

ABSTRACT

Plant-based pharmaceuticals potentially offer a cleaner method of producing a protein for drug manufacturing than traditional methods because plants are free of mammalian infectious agents. However, in the open environment they have the potential for intra-and inter-species gene flow, protein exposure to the public and non-target organisms, and they also have the potential to contaminate livestock feed. This study used probabilistic approaches to quantify the non-target organism risks associated with three pharmaceutical proteins produced in field-grown maize. The risk assessment for plant-based pharmaceuticals was conducted for four receptor species used as surrogates for a wider range of species. Body weights and maize consumption rates for each species were modeled from currently available information and used to calculate the exposure based on expression levels of three proteins. The acute dietary exposure for the receptor species was a single-day event in which the total maize consumption came from the recombinant maize. The non-target organism risk assessment demonstrated that risks will vary between species and between proteins, based primarily on differences in toxic endpoint and consumption rates. It also shows the utility of probabilistic, quantitative risk assessment methodologies and the importance of assessing risks from plant-based pharmaceuticals on a case-by-case basis.

Key Words:

• biotechnology
• risk assessment
• aprotinin
• gastric lipase
• Escherichia coli heat-labile enterotoxin B subunit (LT-B)

ACKNOWLEDGMENTS

We thank J. Wolt (Iowa State University) and R. Davis (Montana State University) for reviewing a previous version of this article. This study was funded by a grant from the Biobased Institute at Montana State University and the Montana Agricultural Experiment Station.

Notes

^a Risk Quotient = Ingestion Exposure ÷ Toxic Endpoint.

^a Percent contribution of input variable to output variance.