Identification of Phthalates in Medications and Dietary Supplement Formulations in the United States and Canada

TLDR

Phthalates such as DEHP and DBP are reproductive toxicants, humans are widely exposed, and the impact of medication‑derived exposure remains unclear. This study aimed to identify and characterize prescription, over‑the‑counter, and dietary supplement products marketed in the US and Canada since 1995 that contain phthalate excipients. The authors compiled modified‑release drug lists, verified phthalate content through electronic databases, package inserts, manufacturer communication, and internet keyword searches, and identified polymers like HMP, CAP, and PVAP in 75 prescription products. They found 6 prescription drugs containing DBP, 45 containing DEP, 3 OTC and supplement products with DBP, 64 with DEP, and over 90 products containing phthalate polymers, indicating widespread use across therapeutic categories.

Abstract

In animal studies, some ortho-phthalates, including di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP), have been shown to be reproductive and developmental toxicants. Human studies show widespread population exposure to background levels of phthalates. Limited evidence suggests that particularly high exposure levels may result from orally ingested medicinal products containing phthalates as excipients (inactive ingredients).In this study we aimed to identify and describe the scope of prescription (RX) and nonprescription (over-the-counter; OTC) medicinal products and dietary supplements marketed in the United States and Canada since 1995 that include phthalates as excipients.We used lists of modified-release drug products to identify potential drug products. Inclusion of phthalates was verified using available electronic databases, print references, published package inserts, product packages, and direct communication from manufacturers. Additional products were identified using Internet searches utilizing keywords for phthalates.Based on labeling information, 6 RX drug products included DBP as an excipient, and 45 specified the use of diethyl phthalate (DEP). Phthalate polymers with no known toxicity--hypromellose phthalate (HMP), cellulose acetate phthalate (CAP), and polyvinyl acetate phthalate (PVAP)--were included in 75 RX products. Three OTC drug and dietary supplement products listed DBP, 64 listed DEP, and > 90 indicated inclusion of polymers.Numerous RX and OTC drug products and supplements from a wide range of therapeutic categories may use DBP or DEP as excipients in oral dosage forms. The potential effects of human exposure to these phthalates through medications are unknown and warrant further investigation.