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Biomedical subjects

C N Park

Publications and source records attributed to C N Park.

At least 19 recordsLinked to original sources
PubMed2000

Methodology for characterizing distributions of incremental body burdens of 2,3,7,8-TCDD and DDE from breast milk in North American nursing infants.

A clear picture of ranges of doses of breast-milk contaminants experienced by nursing infants in North America has not yet been described, resulting in a significant gap in our understanding of potential health risks to infants from those contaminants. While point estimates of incremental dose have appeared in the published literature, these do not account for the wide variability in exposures experienced by nursing infants. This research expands on the current state of understanding of breast-milk contaminant exposure by characterizing distributions, rather than point estimates, of dose. Distributions of milk intake by nursing infants were characterized to examine intake of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and dichlorodiphenyl dichloroethane (DDE). The results indicate that, despite the uncertainties inherent in modeling incremental body burdens of chemicals from nursing, estimating incremental infant body burdens of lipophilic chemicals from breastfeeding using point estimates may result in overly conservative estimates of the contribution of breastfeeding to long-term body burdens of those chemicals in children. To develop reliable estimates of incremental body burden from nursing, depuration via lactation and half-life in the infant should be considered. Further, incremental infant body burdens of lipophilic chemicals increase rapidly at the start of lactation, but decrease after approximately 5 to 6 mo; by 2 yr postpartum, incremental body burdens have decreased substantially. Given the benefits afforded to infants who breastfeed, and because breastfeeding does not necessarily lead to significantly increased long-term body burdens in infants, breastfeeding should be encouraged and promoted.

Body Burden↗
PubMed1990

Development of a physiologically based pharmacokinetic model for risk assessment with 1,4-dioxane.

A six compartment physiologically based pharmacokinetic (PB-PK) model was developed to describe the disposition of diethylene-1,4-dioxide (dioxane) and its principal metabolite beta-hydroxyethoxyacetic acid in rats, mice, and humans. The model was developed from experimentally measured partition coefficients (reported here for the first time) as well as pharmacokinetic data previously reported. The completed PB-PK model adequately described data from gavage and intravenous studies in rats, as well as inhalation studies in rats and humans. Substantial nonlinearities were observed in the kinetic behavior of dioxane under high exposure conditions (water concentrations greater than 0.1% dioxane and atmospheric concentrations greater than 300 ppm dioxane). The PB-PK model was subsequently used to prepare quantitative estimates of the "plausible upper bounds" on carcinogenic risk for human populations exposed to dioxane in air or water. Based on these quantitative estimates, it appears that human populations continuously exposed to 740-3700 ppb dioxane in air or 20,000-120,000 ppb dioxane in water would be unlikely to experience increased frequencies of tumors.

Animals↗
PubMed1989

Mathematical models in quantitative assessment of carcinogenic risk.

Regulatory guidelines have specified default assumptions for the calculation of upper bounds on potential carcinogenic risk. These default "science policy" assumptions are used in the absence of more appropriate biological information, but can, in theory, be overridden by compound-specific data. As a screening tool, the standard LMS procedure provides a useful yardstick for regulators to compare hazard potential across compounds and across exposure scenarios. This standard methodology does not estimate actual risk, however. When specific compounds are being considered for detailed evaluation, methodology for more accurately estimating the true risk is often available. Pharmacokinetic models can be used to more accurately define the high-dose to low-dose extrapolation as well as to provide insight into across route and across species extrapolations. "More central" estimates of the upper bound on risk can be derived, or decision analysis techniques can be used to define the probability distribution of risk estimates, as the assumptions are changed. These data give the risk manager more information as to the relevance of the upper bound, and should be presented in any risk estimate to provide a richer demonstration as to the true risk.

Animals↗
PubMed1988

Incorporation of in vitro enzyme data into the physiologically-based pharmacokinetic (PB-PK) model for methylene chloride: implications for risk assessment.

Physiologically-based pharmacokinetic (PB-PK) models provide a mechanism for reducing the uncertainty inherent in extrapolating the results of animal toxicity tests to man. This paper discusses a technique for incorporating data from in vitro studies of xenobiotic metabolism into in vivo PB-PK models. Methylene chloride is used as an example, and carcinogenic risk estimates incorporating PB-PK principles are presented.

Animals↗
PubMed1986

Cytogenetic variability of lymphocytes from phenotypically normal men: influence of age, smoking, season, and sample storage.

A cytogenetic study was conducted on cultured lymphocytes from a group of 60 male volunteers to determine the baseline of chromosomal aberrations in nonchemical workers. Only males were included in the study to avoid any sex effects on the results. Blood samples were collected from each man every 13 w (quarterly) over a period of 12 m. A single batch of culture medium was used for the entire study. The influence of storing the blood samples prior to culture, donor's age, cigarette smoking, and seasonal variation on lymphocyte mitotic index and chromosomal aberration yield was analyzed. A significant decrease in mitotic activity was observed in cultures from samples stored for 3 d at room temperature (22 +/- 1 degree C). Storing of samples at refrigerator temperature (4 +/- 1 degree C) for up to 3 d prior to culture did not affect lymphocyte growth. Although the mitotic index was found to be inversely proportional to the age of the donors, a significant influence of age on total cytogenetic aberrations was not detectable. A group of 15 smokers appeared to have higher number of chromosomal aberrations; however, the difference in mean mitotic activity between lymphocytes of the two groups was not statistically significant. No detectable seasonal influence was found on any chromosomal aberration category except in the number of chromatid gaps. The mitotic indices of the first quarter cultures, on the other hand, showed significant differences from the other three quarters. The chromosomal aberration baseline of the group was not strikingly different from the ones reported by other investigators.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Analysis of sister chromatid exchanges in lymphocytes cultured from 71 healthy men.

Sister chromatid exchanges (SCE) were analyzed in peripheral blood lymphocytes from a select group of 71 healthy men, 56 nonsmokers and 15 cigarette smokers. In addition to estimating baseline SCE, data were examined to seek relationships of SCE frequencies to age and smoking. The baseline value of 7.53 SCE per cell from the 56 nonsmokers was within the range (5.60 to 9.10 SCE/cell) reported for other human populations. No relationship was found between the mean SCE frequency per cell and age. However, a significant increase in the SCE mean value was observed in smokers as compared to nonsmokers. The results of this study are compared with those of other reports on SCE effects of age and smoking.

Adult↗
PubMed1985

Supernumerary chromosomal elements in lymphocytes cultured from phenotypically normal human adult males.

In a group of phenotypically normal men there were approximately 0.24% of metaphase lymphocytes with extra chromosomal elements along with the regular 46 chromosomes. They ranged in size from small acrocentric-acentric elements to elements longer than any chromosome arm. These elements have been referred to as supernumerary chromosomal elements. No significant effects due to donor's age, smoking history, season, storage of blood samples prior to culture, or culture medium, were found either in the frequency of supernumerary elements per cell or in the frequency of cells with supernumerary elements. Furthermore, the same subject did not consistently exhibit supernumerary elements. Furthermore, the same subject did not consistently exhibit supernumerary elements when sampled during four successive quarters of the year. Some of these elements in pairs were identified by G-banding technique as translocation chromosomes bearing long arms of chromosome number 2 and presumptive short arms of chromosome 8, acentric long arms of chromosome 4, and iso-acentric chromosomes for the long arms of chromosome 5. Presumably, more than one type of cytogenetic event occurred in their formation. Circumstantial evidence has been presented to show that the means of elimination of these supernumerary elements is a process of chromosomal disintegration.

Adult↗
PubMedDate not supplied

Quantitative risk assessment: state-of-the-art for carcinogenesis.

A critical evaluation of the use of statistical models in carcinogenic risk assessment is made with emphasis on the strengths and weaknesses of current practice. The objective is to bring together information from the fields of toxicology and statistics to develop a sound scientific basis for making risk decisions. It is emphasized that risk assessment is a complex, multifaceted process that is not easily quantified and, at present, must be based on qualitative as well as quantitative information. It is evident that dose-response modeling of tumor incidence data from animal studies is of limited value in estimating human risk associated with low-dose chemical exposures. The models take into account only one part of the complex process and have no accepted basis in biology. The key decision points, qualitative factors, and quantitative considerations are identified and discussed and a risk assessment framework that incorporates these inputs is presented. A model that incorporates the tumorigenic dose-response information as well as the qualitative and quantitative biological factors that affect the estimate of risk is proposed. It is concluded that much work needs to be done before a completely quantitative approach to risk assessment is to be useful; in particular pharmacokinetic modeling should be pursued more aggressively.

Animals↗
PubMedDate not supplied

Behavioral effects of 0 and 0.05% blood alcohol in male volunteers.

Five behavioral tests were evaluated to determine their sensitivity to the subtle central nervous system (CNS) depressant effects produced by ingestion of ethanol. Twenty-one adult male volunteers received 0 and 1.4 ml 100 proof vodka/kg body weight according to a "double-blind" crossover design. Behavioral tests were conducted between 15 and 65 minutes after ethanol ingestion, when blood alcohol concentrations (BAC's) were between 0.05 and 0.06%. Tests evaluated were Archimedes spiral, digit span memory, critical flicker fusion, stabilometry and tachistoscope. Multivariate analysis of variance (MANOVA) using composite scores representing the individual tests indicated that the battery as a whole was sensitive to ethanol effects. Repeated measures analysis of variance (ANOVA) on each test indicated that critical flicker fusion, stabilometry and tachistoscope contributed more to the overall sensitivity of the battery than did digit span memory and Archimedes spiral.

Animals↗