A urinary biomarker for monitoring exposures to 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate in rats.

Abstract

2,2,4-Trimethyl-1,3-pentanediol monoisobutyrate (TMPD-MB) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TMPD-DB) are widely used primarily as surface stabilizers for water-based paints and plasticizers, respectively. Exposure to these compounds has been suspected as being associated with sick building syndrome and allergic diseases such as asthma in general populations. Therefore, it is very important to be able to know the amounts of these compounds absorbed into the body in order to evaluate its adverse effects on humans in living environments. In the present study, the urinary excretion kinetics of TMPD-MB and TMPD-DB were studied in animals to establish for urinary metabolites suitable as biomarkers for monitoring exposure. A single dose (48-750mg/kg body weight) of TMPD-MB or TMPD-DB was administered intraperitoneally to male Sprague-Dawley rats, and their urine was collected periodically for a week. Two major metabolites, 2,2,4-trimethyl-1,3-pentanediol (TMPD) and 3-hydroxy-2,2,4-trimethylvaleric acid (HTMV), were measured in the urine samples. Their kinetics were evaluated by moment analysis of the urinary excretion rates of the metabolites versus time curves. The urinary excretion amounts of HTMV were suggested to be proportional to the absorption amounts over a wide exposure range of both TMPD-MB and TMPD-DB. The amounts of HTMV accounted for almost the same level, i.e., 4-5% of the dose at the lowest dosage, in rats tested for both TMPD-MB and TMPD-DB. Urinary HTMV was considered to be an optimal biomarker for monitoring exposure to mixtures of these compounds.