The association between biomarker-based exposure estimates for phthalates and demographic factors in a human reference population.

Abstract

Phthalates are important industrial chemicals used in the manufacture of a wide range of plastic and nonplastic products and can be divided into two basic groups: those used as plasticizers for synthetic polymers that are incorporated into food wrap, medical tubing, and molded toys, and those used primarily in consumers products such as varnishes, perfumes, nail polishes, and insect repellents. It is conceivable that the route of exposure of an organism to phthalates is an important parameter when considering metabolism of these chemicals in vivo. Phthalates are readily metabolized in the gut, such that oral exposure would not lead to accumulation of high concentrations of these chemicals (1). However, few data are available on the metabolism of this group of chemicals after inhalation or dermal exposure. The primary route of phthalate exposure to the general human population has been presumed to be ingestion. Lower molecular-weight phthalates such as diethyl phthalate (DEP) and di-nbutyl phthalate (DBP) can be absorbed percutaneously, and the more volatile congeners can be inhaled. Dermal absorption is important for products applied to skin. (3) applied a simple pharmacokinetic model to estimate the total daily intake of phthalates that would result in the reported urinary concentrations of monoester metabolites. These intake estimates were used as a measure of total exposure to diethyl phthalate (DEP), di-n-butyl phthalate (DBP), n-butyl benzyl phthalate (BBP), dicyclohexyl phtha-Blount et al. (2) reported a considerable number of observations in which the analyte levels in urine were below the limit of detection (LOD) for the procedure being used. This analysis excluded analytes for which more than 25% of the studied individuals were below the LOD and discarded individuals below the LOD for analytes they did analyze. This represents a substantial loss of information. Maximum likelihood methods for censored observations (4-7) have been used for many years to analyze survival data and data for which some observations cannot be seen, but it is known that the observation is beyond some critical point. For urinary metabolite data, an observation below the LOD can be assumed to have a metabolite concentration less than the LOD. Methods have been developed for analyzing biomarkers of exposure-including observations below the LOD-by using statistical likelihoods and regression methods for censored data (8). Using a likelihood for censored data, these fractional pieces of information contribute to the overall interpretation of the data and can be used in a natural framework to estimate parameters and test for population differences. To account for strata differences of demographic factors, we estimated population-based exposures to phthalates using a weighted analysis in which weights were assigned for each individual group depending on the frequency of their demographic variables in the general U.S. population.The aim of this study was to present methods for the analysis of exposure estimates based on urinary biomar...

Estimated daily intake of phthalates in occupationally exposed groups

“…Creatinine concentrations in spot urine samples from NHANES III were significantly higher among non-Hispanic blacks as compared with other racial/ethnic groups (Barr et al, 2005); however, race/ethnicity was confounded within sector in our study (Hines et al, 2009). Demographic characteristics such as education, family income, and place of residence have also been associated with concentrations of certain urinary phthalate metabolites in a subset of NHANES III participants (Koo et al, 2002).…”

“…Biomarker-based estimates of phthalate daily intake are available for adults and children in the United States, Germany, Korea, Japan, and Taiwan (David, 2000;Kohn et al, 2000;Koo et al, 2002;Clark et al, 2003;Itoh et al, 2005;Koo and Lee 2005;Itoh et al, 2007;Koch et al, 2007Koch et al, , 2006Koch et al, , 2003bWittassek et al, 2007;Chen et al, 2008;Wittassek and Angerer, 2008), for pregnant women (Marsee et al, 2006) and for infants in neonatal intensive care units (Calafat and McKee, 2006;Weuve et al, 2006); however, phthalate daily intake estimates for occupationally exposed groups are lacking. In 2003-2005, the National Institute for Occupational Safety and Health (NIOSH) conducted a preliminary study of phthalate exposures among 156 workers in eight industry sectors where materials containing diethyl phthalate (DEP), dibutyl phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP) were manufactured or used as part of the workers' regular job duties.…”

Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

“…Separate variances were estimated for ketamine and norketamine enantiomers. Data below the limit of detection were treated as censored observations using the method of Koo et al (2002). Estimated parameters are presented in Table 1.…”

“…Confidence bounds for the estimated parameters and statistical tests based on the model were all done using the likelihood ratio test as described by Koo et al (2002). Standard deviation for the model for ketamine (R or S) and for norketamine (R or S) were 3.03 and 1.00, respectively.…”

Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers.

“…This is especially true when comparing monoester results of the higher-molecularweight phthalate monoesters, such as MEHP, with the lower-molecular-weight monoesters, such as MEP, because the metabolism of the higher-molecular-weight phthalates is more complex and results in more metabolites, thus decreasing the relative amounts of their monoester metabolites. To properly interpret and model the data (David 2000;Kohn et al 2000;Koo et al 2002), one must have knowledge of the pharmacokinetics of each of the phthalates. For example, the higher urinary concentrations and frequency of detection of the oxidative DEHP metabolites MEOHP and MEHHP relative to that of MEHP suggest that the two oxidative metabolites are more sensitive indicators of DEHP exposure than is MEHP alone and that exposure to DEHP may be higher than previously thought based on the NHANES data, which measured MEHP only.…”