Assessing Risks of Plant-Based Pharmaceuticals: I. Human Dietary Exposure

ABSTRACT

Protein-based drugs are the fastest growing class of drugs for the treatment of disease in humans and other animals. However, the current method of producing proteins for pharmaceutical application is predicted to fall short because of population growth and demographic trends. This study characterized human dietary risks using quantitative risk assessment techniques for three pharmaceutical proteins produced in field-grown maize. The three proteins were aprotinin, gastric lipase, and Escherichia coli heat-labile enterotoxin B subunit (LT-B). The human dietary risks from the three proteins inadvertently occurring in food were evaluated using three different exposure scenarios so that potential risks could be compared. The three exposure scenarios ranged in conservatism to evaluate the range of risk between the proteins and scenarios. Risk quotients (RQs) were calculated for all three scenarios to integrate exposure and effect (toxicity). The risk assessments revealed that the most conservative scenario produced higher RQs than the other two scenarios. The dietary risks from scenario 1 for aprotinin were three orders of magnitude greater than for scenario 2, and four orders of magnitude greater than for scenario 3. This risk assessment revealed that dietary risks will vary dramatically and depend on factors such as the specific pharmaceutical protein, protein expression, and exposure scenarios. The assessment also reinforced the need for case-by-case assessments.

Key Words:

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

ACKNOWLEDGMENTS

We thank J. Wolt (Iowa 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 RQ = Risk Quotient [dietary exposure ÷ toxic endpoint].

^a RQ = Risk Quotient [dietary exposure ÷ toxic endpoint];

^b non-nursing (< 1 yr. old);

^c 1–6 yr. old;

^d pregnant not nursing.

^a RQ = Risk Quotient [dietary exposure ÷ toxic endpoint];

^b non-nursing (< 1 yr. old);

^c 1–6 yr. old;

^d pregnant not nursing.

^a RQ = Risk Quotient [dietary exposure ÷ toxic endpoint];

^b non-nursing (< 1 yr. old);

^c 1–6 yr. old;

^d pregnant not nursing.

^a RQ = Risk Quotient [dietary exposure ÷ toxic endpoint];

^b non-nursing (< 1 yr. old);

^c 1–6 yr. old;

^d pregnant not nursing.

^a RQ = Risk Quotient [dietary exposure ÷ toxic endpoint];

^b non-nursing (< 1 yr. old);

^c 1–6 yr. old;

^d pregnant not nursing.

^a RQ = Risk Quotient [dietary exposure ÷ toxic endpoint];

^b non-nursing (< 1 yr. old);

^c 1–6 yr. old;

^d pregnant not nursing.