Medications as a source of human exposure to phthalates.

Abstract

Phthalates are a group of multifunctional chemicals used in consumer and personal care products, plastics, and medical devices. Laboratory studies show that some phthalates are reproductive and developmental toxicants. Recently, human studies have shown measurable levels of several phthalates in most of the U.S. general population. Despite their widespread use and the consistent toxicologic data on phthalates, information is limited on sources and pathways of human exposure to phthalates. One potential source of exposure is medications. The need for site-specific dosage medications has led to the use of enteric coatings that allow the release of the active ingredients into the small intestine or in the colon. The enteric coatings generally consist of various polymers that contain plasticizers, including triethyl citrate, dibutyl sebacate, and phthalates such as diethyl phthalate (DEP) and dibutyl phthalate (DBP). In this article we report on medications as a potential source of exposure to DBP in a man who took Asacol [active ingredient mesalamine (mesalazine)] for the treatment of ulcerative colitis. In a spot urine sample from this man collected 3 months after he started taking Asacol, the concentration of monobutyl phthalate, a DBP metabolite, was 16,868 ng/mL (6,180 micro g/g creatinine). This concentration was more than two orders of magnitude higher than the 95th percentile for males reported in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). The patient's urinary concentrations of monoethyl phthalate (443.7 ng/mL, 162.6 micro g/g creatinine), mono-2-ethylhexyl phthalate (3.0 ng/mL, 1.1 micro g/g creatinine), and monobenzyl phthalate (9.3 ng/mL, 3.4 micro g/g creatinine) were unremarkable compared with the NHANES 1999-2000 values. Before this report, the highest estimated human exposure to DBP was more than two orders of magnitude lower than the no observable adverse effect level from animal studies. Further research is necessary to determine the proportional contribution of medications, as well as personal care and consumer products, to a person's total phthalate burden.

Di-n-butylphthalate and butylbenzylphthalate — urinary metabolite levels and estimated daily intakes: pilot study for the German Environmental Survey on children

“…Furthermore, we want to point out that both models are not based on worst case assumptions but try to accommodate the most likely exposure scenario for each individual child. As two case studies in the US and Germany have shown (Hauser et al, 2004;Koch et al, 2005a), actual individual exposures to DnBP through medications can be manifold higher than reported in this study.…”

“…In two case studies both in the USA and in Germany, extraordinary high urinary MnBP concentrations (16.9 mg/l and 31.0 mg/l) were reported after DnBP-containing medications have been taken (Hauser et al, 2004;Koch et al, 2005a). These values are about a 100-1000 times higher than the median values in all previously investigated populations.…”

“…Kavlock et al (2002) point out that DnBP has not been used for a considerable time in the USA to plasticize PVC. Peak DnBP exposures can be caused through DnBP-containing medications both in the US (Hauser et al, 2004) and Germany (Koch et al, 2005a). For BBzP, daily intake values are roughly the same in the USA and Germany over the whole range.…”

Human body burdens of chemicals used in plastic manufacture

“…Phthalates also are used as industrial solvents and lubricants, additives in the textile industry, in pesticide formulations and as components in personal-care products (David et al 2001;EC 2008). One of them, dibutyl phthalate (DBP), is also used in the pharmaceutical field as a constituent of the enteric coating of some medications (Hauser et al 2004).…”

The effects on steroidogenesis and histopathology of adult male Japanese quails (Coturnix coturnix japonica) testis following pre-pubertal exposure to di(n-butyl) phthalate (DBP)

“…PEs are used extensively as plasticizers, in several consumer plastic products, including children toys, food wrappings, cosmetics, paints, some biomedical devices (e.g. dialysis tubing and intravenous bags), and enteric coatings of some pharmaceuticals (Hauser et al, 2004;Oehlmann et al, 2009). Because PEs are not covalently bound to polymer plastics, they can easily leach out over time into the environment, reaching humans and wildlife species through ingestion, inhalation, and dermal exposure (Heudorf et al, 2007).…”