Larry L. Needham

Chlorinated hydrocarbon levels in human serum: Effects of fasting and feeding

Twenty healthy adult humans had serum samples drawn on four occasions within a 24-hr period: after a 12 hr overnight fast, 4–5 hr after a high fat breakfast, at midafternoon, and the next morning after another 12 hr fast. Nonfasting samples had 22% to 29% higher mean concentrations (p < 0.05) than did fasting samples for polychlorinated biphenyls (PCBs, 4.81 vs 3.74 ng/g serum wt), hexachlorobenzene (HCB, 0.163 vs 0.134 ng/g serum wt), andp,p′-dichlorodiphenyldichloroethylene (p,p′-DDE, 6.74 vs 5.37 ng/g serum wt) measured by electron capture gas liquid chromatography. Total serum lipids were estimated from measurements of total cholesterol, free cholesterol, triglycerides, and phospholipids and were 20% higher in nonfasting samples than in fasting samples (7.05 g/L vs 5.86 g/L). When PCBs, HCB, andp,p′-DDE concentrations were corrected by total serum lipids, results from fasting and nonfasting samples were not statistically different. Because of the differences in these chlorinated hydrocarbon concentrations observed with different sample collection regimens, meaningful comparison of analytical results requires standardizing collection procedures or correcting by total serum lipid levels.

Correlation between serum and adipose tissue levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in 50 persons from Missouri.

Paired human serum and adipose tissue samples were analyzed from 50 persons for 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) by high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). On a lipid weight basis, the range of values in adipose tissue spanned approximately 2.5 orders of magnitude, from 3.3 to 969 parts per trillion (ppt). After adjusting the adipose tissue 2,3,7,8-TCDD levels for total lipid content and the serum 2,3,7,8-TCDD levels for total lipid content, the mean of the partitioning ratio of adipose tissue to serum 2,3,7,8-TCDD was 1.09 (standard deviation = 0.385, standard error = 0.060). On this same total lipid weight basis, the adipose tissue and serum levels of 2,3,7,8-TCDD were highly correlated, r = 0.98. The high correlation between adipose tissue and serum 2,3,7,8-TCDD levels in this study indicates that serum 2,3,7,8-TCDD is a valid measurement of 2,3,7,8-TCDD body burden concentration.

Do human milk concentrations of persistent organic chemicals really decline during lactation? Chemical concentrations during lactation and milk/serum partitioning.

Background Conventional wisdom regarding exposures to persistent organic chemicals via breast-feeding assumes that concentrations decline over the course of lactation and that the mother’s body burden reflects her cumulative lifetime exposure. Two important implications stemming from these lines of thought are, first, that assessments of early childhood exposures should incorporate decreasing breast milk concentrations over lactation; and, second, that there is little a breast-feeding mother can do to reduce her infant’s exposures via breast-feeding because of the cumulative nature of these chemicals. Objectives We examined rates of elimination and milk/serum partition coefficients for several groups of persistent organic chemicals. Methods We collected simultaneous milk and blood samples of 10 women at two times postpartum and additional milk samples without matching blood samples. Results Contrary to earlier research, we found that lipid-adjusted concentrations of polybrominated diphenyl ethers, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins and furans, and organochlorine pesticides in serum and milk do not consistently decrease during lactation and can increase for some women. Published research has also suggested an approximate 1:1 milk/serum relationship (lipid adjusted) on a population basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin; however, our results suggest a more complex relationship for persistent, lipophilic chemicals with the milk/serum relationship dependent on chemical class. Conclusions Decreases in concentration of lipophilic chemicals on a lipid-adjusted basis during lactation should no longer be assumed. Thus, the concept of pumping and discarding early milk as means of reducing infant exposure is not supported. The hypothesis that persistent lipophilic chemicals, on a lipid-adjusted basis, have consistent concentrations across matrices is likely too simplistic.

Pentachlorophenol measurements in body fluids of people in log homes and workplaces.

Human exposure to pentachlorophenol (PCP) was evaluated in the normal population (controls), residents of PCP-treated log homes, and persons exposed primarily in the workplace. Blood and urine samples were analyzed by gas chromatography after extraction and acetylation. For 34 controls, serum PCP values ranged from 15–75 ppb with a mean of 40 ppb. For 123 residents of log homes, serum levels ranged from 69–1,340 ppb with a mean of 420 ppb. In such homes, serum levels for children were significantly higher than those for parents, averaging 1.8 times greater. Serum and urine values for workers varied widely, depending on the workplace, with serum levels ranging from 26 to 84,900 ppb of PCP. Urinary concentrations when corrected for creatinine values correlated well (r=0.92) with serum concentrations. Coating PCP-treated logs of home interiors with a sealant reduced serum PCP levels in the residents.

Age- and Concentration-Dependent Elimination Half-Life of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Seveso Children

Objective Pharmacokinetic and statistical analyses are reported to elucidate key variables affecting 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in children and adolescents. Design We used blood concentrations to calculate TCDD elimination half-life. Variables examined by statistical analysis include age, latency from exposure, sex, TCDD concentration and quantity in the body, severity of chloracne response, body mass index, and body fat mass. Participants Blood was collected from 1976 to 1993 from residents of Seveso, Italy, who were < 18 years of age at the time of a nearby trichlorophenol reactor explosion in July 1976. Results TCDD half-life in persons < 18 years of age averaged 1.6 years while those ≥18 years of age averaged 3.2 years. Half-life is strongly associated with age, showing a cohort average increase of 0.12 year half-life per year of age or time since exposure. A significant concentration-dependency is also identified, showing shorter half-lives for TCDD concentrations > 400 ppt for children < 12 years of age and 700 ppt when including adults. Moderate correlations are also observed between half-life and body mass index, body fat mass, TCDD mass, and chloracne response. Conclusions Children and adolescents have shorter TCDD half-lives and a slower rate of increase in half-life than adults, and this effect is augmented at higher body burdens. Relevance Modeling of TCDD blood concentrations or body burden in humans should take into account the markedly shorter elimination half-life observed in children and adolescents and concentration-dependent effects observed in persons > 400–700 ppt.

Residues of chlorinated phenols and phenoxy acid herbicides in the urine of Arkansas children.

Urine samples from 197 Arkansas children were analyzed for eight chlorinated phenols and four chlorinated phenoxy herbicides by using a new procedure that combined gas chromatography with tandem mass spectrometry. With the detection limit of 1 part per billion (ppb), six of these pesticides were detected in more than 10% of the samples. 2,5-Dichlorophenol (a metabolite ofp-dichlorobenzene), and pentachlorophenol were detected in 96% and 100%, respectively, of the childrens urine at median concentrations of 9 ppb and 14 ppb, respectively. 2,4,5-Trichlorophenol was detected in 54% of the childrens urine at a median concentration of 1 ppb. One trichlorophenol and three other dichlorophenols were found in 3% to 27% of the samples. The herbicide 2,4-dichlorophenoxyacetic acid was observed in 20% of all samples. The concentrations of all analytes are reported as background or reference levels for use in future studies. The finding of 2,5-dichlorophenol as a ubiquitous contaminant merits further study.

Partitioning of in vivo bound PCDDs/PCDFs among various compartments in whole blood

Abstract We have determined the in-vivo distribution in the various blood compartments of all of the PCDDs/PCDFs normally found in humans. We compare the in-vivo and in-vitro distribution of 2,3,7,8-TCDD among the protein and lipoprotein fractions. In addition, our previously presented serum method is validated for all of the 2,3,7,8-substituted PCDDs and PCDFs.

Adipose tissue/serum partitioning of chlorinated hydrocarbon pesticides in humans

Abstract As more measurements of chlorinated hydrocarbons pesticides are being performed in serum as opposed to adipose tissue, it is important to know how these compounds partition between these two compartments. We have determined concentration ratios for seven of these compounds in humans; these ratios were calculated on an adipose lipid weight vs. serum whole weight, lipid weight and albumin content.

Contaminants in L-Tryptophan associated with eosinophilia myalgia syndrome

In late 1989, an epidemic of eosinophilia-myalgia syndrome (EMS) that resulted in several thousand cases of the syndrome and 36 deaths was recognized in the United States. Physicians in New Mexico linked the epidemic to the ingestion of L-tryptophan (LT). Results of studies indicated that one or more trace contaminants in LT were likely causes of the EMS epidemic. Investigators traced the LT that was taken by most patients with EMS to a single manufacturer, Showa Denko K.K. of Japan.We now report results of high performance liquid chromatographic analysis of LT samples from this manufacturer. Three sets of blind-coded samples were analyzed: the priority case lot set, which included 54 case-associated LT lots and 50 noncase-associated LT lots that were taken by case and control subjects who used only one brand of LT; the single lot case set, which included 73 case-associated LT lots and 25 noncase associated LT lots taken by case and control subjects who used only a single lot of LT; and the South Carolina tablet set, which included LT tablets taken by case subjects (n=26) and by control subjects (n=52). We statistically compared the concentration of each contaminant in case-associated, noncase-associated, and control samples of each sample set. The analyses showed that there were more than 60 minor contaminants in the LT from Showa Denko K.K., and that six of these contaminants were associated with EMS. The structures of three contaminants are known, but the identities of the other three contaminants are currently unknown. In this paper, we discuss each sample set and results of the analysis of each, the combined results of all sets, the identity of the six contaminants, and implications for future research into the etiology of EMS.

Medical evaluation of subjects with known body levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin

Forty-one persons with a history of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure and measured adipose tissue TCDD levels were evaluated for potential health effects. No pattern of clinical abnormalities emerged related to TCDD levels.