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Biomedical subjects

B G Callahan

Publications and source records attributed to B G Callahan.

4 recordsLinked to original sources

Methodology to estimate the amount and particle size of soil ingested by children: implications for exposure assessment at waste sites.

Despite considerable efforts to improve the design of soil ingestion studies, substantial variability in daily soil ingestion rates based on different tracer estimates exists in the same subjects. The present study assessed the hypothesis that one of the unexplored causes of this intertracer variation in soil ingestion estimation was related to differences in soil tracer concentration by particle size. The study analyzed the tracer concentration in soil for children in the Anaconda, Montana soil ingestion study for the particle size fraction less than 250 microm [corrected] in diameter. Soil ingestion estimates for these children were recalculated based on the new soil concentration values and compared to previous findings (E. J. Calabrese, E. J. Stanek, P. Pekow, and R. M. Barnes, submitted, 1996) when the soil concentrations were determined for soil particle size diameter of <2 mm. The results indicated that five tracers (Al, Si, Ti, Y, and Zr) did not have their soil concentrations changed by particle size. However, for three tracers (La, Ce, and Nd) the concentration increased by two- to fourfold with the smaller particle size. Recalculation of soil ingestion estimates indicates that the soil ingestion estimates of the five tracers not varying by particle size did not change while those of the remaining three tracers were decreased by approximately 60%. The revised calculations provide a substantial improvement in intertracer estimates of soil ingestion and suggest that the children ingested soil of small particle size. These findings are of significance since they (1) identify an important potential cause of intertracer variability in soil ingestion estimates, (2) establish a new criterion for soil tracer selection, and (3) develop a method for not only providing improved soil ingestion estimates but also determining the particle size of the ingested soil. These findings offer important potential applications for risk assessment practices at contaminated sites since soil ingestion is frequently the dominant route of estimated contaminant exposure in children.

Child↗

Utilization of quantitative structure-activity relationships (QSARs) in risk assessment: alkylphenols.

Alkylphenols are a class of environmentally pervasive compounds, found both in natural (e.g., crude oils) and in anthropogenic (e.g., wood tar, coal gasification waste) materials. Despite the frequent environmental occurrence of these chemicals, there is a limited toxicity database on alkylphenols. We have therefore developed a "toxicity equivalence approach" for alkylphenols which is based on their ability to inhibit, in a specific manner, the enzyme cyclooxygenase. Enzyme-inhibiting ability for individual alkylphenols can be estimated based on the quantitative structure-activity relationship developed by Dewhirst (1980) and is a function of the free hydroxyl group, electron-donating ring substituents, and hydrophobic aromatic ring substituents. We evaluated the toxicological significance of cyclooxygenase inhibition by comparison of the inhibitory capacity of alkylphenols with the inhibitory capacity of acetylsalicylic acid, or aspirin, a compound whose low-level effects are due to cyclooxygenase inhibition. Since nearly complete absorption for alkylphenols and aspirin is predicted, based on estimates of hydrophobicity and fraction of charged molecules at gastrointestinal pHs, risks from alkylphenols can be expressed directly in terms of "milligram aspirin equivalence," without correction for absorption differences. We recommend this method for assessing risks of mixtures of alkylphenols, especially for those compounds with no chronic toxicity data.

Environmental Pollutants↗

Thallium induced changes in behavioral patterns: correlation with altered lipid peroxidation and lysosomal enzyme activity in brain regions of male rats.

The effects of exposures to low levels of heavy metals is a complex and serious problem. Thallium is a metal which produces behavioral sequelae in human poisoning and is potentially hazardous with low level exposures. A test battery is presented which utilizes biochemical and behavioral testing to assess the effects of low levels of thallium on central nervous system chemistry and function in rats. The doses of thallium used (4 and 8 mg/kg) produced no overt signs of behavioral toxicity but did produce dose-related increases in lipid peroxidation and activation of the lysosomal enzyme beta-galactosidase in selected brain regions. At these dose levels, thallium also selectively altered the patterns of behavior. The study suggests that the target regions of thallium in the brain include the cortex, the cerebellum and the brainstem. The dose-response relationships, found for certain pairs of behavioral acts, were correlated with biochemical changes in one or more brain regions.

Animals↗

Behavioral and biochemical alterations following in utero exposure to methylmercury.

Behavioral changes induced in utero by methylmercury (MeHg) were studied with a non-invasive measure of patterns of effects in 1 to 35 day old rats. Lipid peroxidation (LP) and acetylcholinesterase (AChe) activity were used to compare effects in four different brain regions. MeHg (0, 2 or 6 mg/kg) was administered (PO) at day 6, 7, 8 and 9 of gestation. Rats were videotaped on day 10, 12, 20 and 34 and sacrificed on day 1, 13, 21 and 35. No changes in body or brain weights or other ancillary measures of growth and development occurred between 1-35 days. Cellular injury in brain regions as measured by LP was not altered by MeHg. AChe activity decreased in the anterior cortex and cerebellum on PN12. Frequency, dispersion and interactions of behavioral elements were determined. Frequency of grooming mode elements was decreased at 10, 12 and 34 days for 6 mg/kg, and at 12 and 34 days for 2 mg/kg pups. The frequency of exploratory mode elements increased at days 10 and 12 for 6 mg/kg, days 12 and 20 for 2 mg/kg pups. MeHg increased activities in the attention mode on PN12 at both doses. Behavior patterns were altered on all days observed, but these were not dose related. PN12 was observed to be the beginning of patterning (56 possible interactions). The 6 mg/kg group demonstrated a delay of pattern development at PN12 with a recovery to an altered array of behaviors at PN20. MeHg generally decreased interaction values (Chi2).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗