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Biomedical subjects

E J Calabrese

Publications and source records attributed to E J Calabrese.

At least 91 records · Page 5Linked to original sources
PubMed1993

Lack of total independence of uncertainty factors (UFs): implications for the size of the total uncertainty factor.

This paper assesses the fundamental assumption that multiple uncertainty factors (UFs) are independent of each other and therefore may be combined through a multiplicative scheme. It is argued that a lack of independence is seen in several cases such as that between the interindividual and less-than-lifetime UFs with respect to an age component and results in an error in double counting of UFs. The paper proposes revised UF values based on the concept of the relationship of independent and interdependent UFs. This uncertainty factor revision is then applied to a large number of contaminants for which EPA either has or has proposed MCLs or DWELs.

Age Factors↗
PubMed1993

G2 subpopulation in rat liver induced into mitosis by low-level exposure to carbon tetrachloride: an adaptive response.

Recent findings by Mehendale (Med. Hypoth. 33, 289-299, 1990) indicate that prior exposure to chlordecone markedly enhances CCl4-induced lethality. It was established that chlordecone suppressed the capacity of CCl4-induced toxicity to cause an early (i.e., 6 hr after exposure) hepatocellular division which is believed to be a critical tissue response reducing subsequent CCl4-induced hepatotoxicity. Despite the strong evidence presented by Mehendale, occurrence of such an early cellular division has been considered unlikely since most studies indicate that cellular replacement requires from 30-60 hr depending on the agent, dose, and animal species. This paper presents evidence that supports the observations of Mehendale and indicates that the early mitoses were most likely caused by the activation of hepatocytes arrested in the G2 phase of the cell cycle that became activated by CCl4 treatment, induced injury, or both. The concept being put forward here requires additional experimental verification and validation.

Animals↗
PubMed1993

Selective inhibition of gastrointestinal beta-glucuronidase by polyvinylbenzyl D-glucaro(1,4)lactonate: attachment of D-glucaro(1,4)lactone to polyvinylbenzyl chloride.

D-Glucaro(1,4)lactone, a potent beta-glucuronidase inhibitor was attached via the carboxylic acid moiety to polyvinylbenzyl chloride (PVBC) using a bimolecular nucleophilic displacement reaction. First, the caesium salt of D-glucaro(1,4)lactone was prepared by titrating the carboxylic acid to neutrality with aqueous caesium bicarbonate. The polyvinylbenzyl D-glucaro(1,4)lactonate was obtained in maximum yields of between 50 and 60% when caesium D-glucaro(1,4)lactonate was incubated with PVBC in DMF at 50 degrees C for 7 d in the presence of a catalyst, caesium iodide.

Cesium↗
PubMed1993

Interactive potential of omega-3 fatty acids with clofibrate or DEHP on hepatic peroxisome proliferation in male Wistar rats.

The interactive potential of three known peroxisome proliferators, omega-3 fatty acids, clofibrate and di(2-ethylhexylphthalate (DEHP), was evaluated in male weanling Wistar rats for the effect on peroxisomal beta-oxidation. Omega-3 fatty acids were supplied by menhaden oil which was fed in six regimens: low fat (5% w/w), low fat and clofibrate (0.3% w/w) or DEHP (0.25% w/w), high fat (20% w/w), high fat and clofibrate or DEHP in the aforementioned concentrations. Induction of peroxisomal beta-oxidation was measured by changes in liver-to-body weight ratio, fatty acyl-CoA oxidase (FAO) activity, and peroxisomal bifunctional enzyme (PBE) quantity. Analysis of transformed data indicated a less than additive response in FAO activity with no deviation from additivity seen with liver-to-body ratios and PBE.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1993

Extent and implications of interspecies differences in the intestinal hydrolysis of certain glucuronide conjugates.

1. Interspecies differences in the intestinal hydrolysis of glucuronide conjugates (phenolphthalein glucuronide, 4-methylumbelliferone glucuronide, morphine-3-glucuronide) were evaluated in mouse, rat and rabbit small intestine and caecum. 2. beta-Glucuronidase activity in the caecum was 50-200-fold higher than in the small intestine for all species and substrates studied. 3. There was evidence of a similarity between species in the capacity of the gut contents cultures from the proximal and distal small intestine to hydrolyse phenolphthalein glucuronide and 4-methylumbelliferone glucuronide. 4. Morphine was not liberated from morphine-3-glucuronide in detectable amounts in the proximal and distal small intestine. 5. Species- and substrate-specific differences were identified in the capacity of the caecal microbiota to hydrolyse the glucuronide conjugates studied. 6. The capacity of the rabbit caecal microbiota to hydrolyse all three glucuronides was significantly lower than those of both rat and mouse. 7. Morphine was metabolized to codeine in low, but detectable levels in all three species.

Animals↗
PubMed1992

The Council for Health and Environmental Safety of Soils.

The Council for Health and Environmental Safety of Soils (CHESS) was organized in 1987 to develop a consensus soil risk assessment methodology to be used as a framework for establishing standards for soil contamination to protect the environment and public health. The wide range of contaminating substances of possible health concern in soil is affecting land use and development, causing excessive economic expenditures, and the regulatory approaches for control are disperse. The International Society of Regulatory Toxicology and Pharmacology agreed to sponsor the Council and through a Governing Board composed of experienced scientists from the federal government, state departments of public health and environmental protection, academia, and the private sector including industry and environmental organizations. The Board was created to support the goals of CHESS, its mode of operation, and to establish funding policies and directions. A technical council agreed to develop a peer-reviewed consensus methodology to assess public health risks from contaminated soil by technical committees composed of recognized experts in the area of soil contamination and other relevant disciplines. This methodology would then be made available to federal and state agencies, the private sector, and the scientific community at large. After extensive study, a final decision was made to develop a decision-tree framework to be used at the state and local levels for application to all types of soil contamination. Following extensive studies it was agreed the ubiquitous nature of petroleum contamination in soil has direct and immediate public health implications and CHESS therefore directed its first efforts to this area.(ABSTRACT TRUNCATED AT 250 WORDS)

Environmental Pollution↗
PubMed1992

Does the animal-to-human uncertainty factor incorporate interspecies differences in surface area?

Risk assessment practices for noncarcinogens typically employ an uncertainty factor (UF) for animal-to-human extrapolation when defining acceptable levels for humans based on animal studies. EPA has interpreted the use of this factor as addressing interspecies differences due to dose normalization via surface area (exposure-dose relationships) and to innate differences in species susceptibility (dose-response relationships). Thus EPA has concluded that dose normalization via surface area is not necessary when using animal studies to define acceptable levels for noncarcinogens for humans. In this report we challenge this position on both theoretical and practical grounds. It is recommended that the UF for animal-to-human extrapolation for noncarcinogens in the risk assessment process and the technique for dose normalization be considered distinctly.

Animals↗
PubMed1992

Distinguishing outdoor soil ingestion from indoor dust ingestion in a soil pica child.

This paper represents the first quantitative attempt to distinguish the amount of outdoor soil ingestion from indoor dust ingestion in a soil pica child. Based on a methodology using a comparison of differential element ratios it is estimated that the predominant proportion of the fecal tracers were from outdoor soil and not indoor dust origin. The methodology employed can be utilized on a broader scale to assess the relative amounts of soil and dust consumed by individuals.

Child↗
PubMed1992

Effects of joint exposures to selected peroxisome proliferators on hepatic acyl-CoA oxidase activity in male B6C3F1 mice.

The interaction potential of peroxisome proliferators of similar and dissimilar structure was examined in B6C3F1 mice. Mice were fed diets containing varying concentrations of ciprofibrate (Cipro), clofibrate (Clof) or di(2-ethylhexyl)phthalate (DEHP), or combinations of Cipro and Clof or Cipro and DEHP for 4 d. Induction of peroxisomal beta-oxidation, measured by increased acyl-CoA oxidase activity, was used as the endpoint for analysis. An additive response occurred following joint exposure to the structurally related compounds Cipro and Clof, whereas a possible synergistic response occurred at low dose combinations of the structurally dissimilar Cipro and DEHP. These findings represent the first report assessing the in-vivo interaction potential of structurally similar and dissimilar peroxisome proliferators and provides insight into the dose-response nature of joint exposures to certain non-genotoxic carcinogens.

Acyl-CoA Oxidase↗
PubMed1992

The interactive effect of chlorine, copper and nitrite on methaemoglobin formation in red blood cells of Dorset sheep.

Simultaneous exposure to chemicals which can oxidize the haemoglobin of the red blood cell to methaemoglobin is common. Although the effects of some of these agents have been documented individually, little research considers the interactive effects. In-vitro experiments on the treated blood of female Dorset sheep assessed the interactive capacity of chlorite, copper and nitrite to affect methaemoglobin formation. All combinations of doses which produced 2.5, 5, 10% methaemoglobin were tested in all possible combinations (a total of 80), as were the controls. This included data on each chemical alone, each two-way combination and the three-way combination. The response is largely additive (the sum of the individual effects) except for one of the two-way interactions, chlorite/nitrite (P less than .01), which showed antagonism. Chlorite may oxidize nitrite which could explain the less-than-additive response. Overall, the result of combining these agents on methaemoglobin was additive.

Animals↗
PubMed1992

Lead-induced cell proliferation and organ-specific tumorigenicity.

While lead acetate is a renal carcinogen in rodent studies, the mechanism by which it induces cancer has not been established. This report proposes that the enhanced susceptibility of renal tubular epithelial cells to lead-induced mitogenicity at the levels comparable to those administered in the cancer bioassay may contribute to the carcinogenic response seen in this target organ. Of relevance is that the nonresponsiveness of the liver to lead-induced carcinogenicity was associated with significantly less capacity (i.e., 675-fold) of lead to induce the mitogenic response in the rodent liver.

Animals↗
PubMed1992

Mink as a predictive model in toxicology.

This paper reviewed the biomedical and toxicological database concerning the use of mink as a predictive model of human responses. It is concluded that substantial information exists on the mink genetics, physiology, metabolism, nutritional requirements, and susceptibility to infectious disease; and provides a foundation upon which interspecies extrapolation may be considered. In addition, information on the response of mink to several dozen toxic substances revealed that mink respond in a qualitatively and quantitatively similar manner to other more commonly employed species as well as humans. Our conclusion does not infer that mink should be used routinely in toxicological testing for estimation of human responses. However, it indicates that toxicological data from this species may be a useful complement in risk assessment processes based upon data obtained from traditionally employed models such as rats and dogs.

Animals↗
PubMed1991

A guide to interpreting soil ingestion studies. I. Development of a model to estimate the soil ingestion detection level of soil ingestion studies.

This paper provides a model with which to predict soil ingestion recovery values in soil ingestion studies either retrospectively or prospectively. The predictive equations generated from the model can be used to estimate minimum soil ingestion detection levels from soil ingestion studies which use mass-balance methods. The model is derived from data assessing soil recovery efficiencies in adults using eight different predictive tracer elements. The results constitute a methodology for determining minimum detection levels of soil ingestion and hence have important regulatory significance.

Humans↗
PubMed1991

A guide to interpreting soil ingestion studies. II. Qualitative and quantitative evidence of soil ingestion.

Four major studies have attempted to qualitatively and quantitatively assess the extent of soil ingestion in children using the soil tracer methodology. The validity of the estimates of soil ingestion in each study was reevaluated in light of the inherent strengths and limitations of study design and/or execution, as well as via a novel methodology for estimating the soil recovery variance for each tracer, which then led to the estimation of soil ingestion detection limits for each tracer for studies performing mass-balance analyses. Based on these analyses it is concluded that the Binder et al. (1986, Arch. Environ. Health 41, 341-345) and Van Wijnen et al. (1990, Environ. Res. 51, 147-162) studies provide no convincing evidence to support qualitative and quantitative estimates of soil ingestion due to inherent limitations in their respective study designs. The Davis et al. (1990, Arch. Environ. Health 45, 112-122) and Calabrese et al. (1989, Regul. Toxicol. Pharmacol. 10, 123) studies displayed convincing qualitative evidence of soil ingestion. However, the results indicate that the median soil ingestion estimates of Davis et al. were less reliable than those of Calabrese et al. The range of detection limits vary according to the tracer and the assumption of acceptable precision in recovery estimation. The minimum detection level of soil ingestion in children in the Calabrese et al. study, with a variance in recovery of 100% +/- 20%, was 21 mg/day based on Zr.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Evidence of soil-pica behaviour and quantification of soil ingested.

A previously published report on soil ingestion in children, revealed evidence that one of the subjects, a 3.5-year-old female, displayed soil-pica behaviour. Soil ingestion estimates for this child ranged from approximately 5 to 7 g d-1 for seven of eight soil tracers employed. The present paper revealed that the soil-pica behaviour occurred only in the second of the two weeks of observation, during which daily soil ingestion rates ranged from 10 to 13 g d-1. Tracer recovery studies displayed acceptable precision (i.e. 100% less than +/- 30%) for six of the eight tracers during the soil-pica episode (week 2). Evaluation of the weekly soil ingestion values of the remaining 63 subjects indicated no convincing evidence of soil-pica behaviour in this group of children aged 1-4.

Child Behavior↗
PubMed1990

Induction of peroxisome proliferation in rainbow trout exposed to ciprofibrate.

Rainbow trout (Salmo gairdneri), average body weight of 450 g, were treated with 15, 25, or 35 mg/kg of ciprofibrate via intraperitoneal injection every other day for 2 to 3 weeks. The effects on hepatic peroxisomal acyl-CoA oxidase, polypeptide PPA-80, catalase, and liver weight were measured. The treatment of trout with ciprofibrate showed significant dose-related increases in peroxisomal acyl-CoA activity, polypeptide PPA-80, and catalase after 3 weeks of exposure. Peroxisomal oxidase activity showed a significant (p = 0.0008) increase (78%) at 35 mg/kg and a marginal (p = 0.1) increase (27%) at 25 mg/kg after 3 weeks of exposure. Densitometric analysis of polypeptide PPA-80 and catalase showed increases up to 48 and 236% at 35 mg/kg, respectively. Morphometric analysis on livers of trout administered 35 mg/kg for 3 weeks showed a 2.3-fold increase of peroxisomal volume density, as compared to control. This study demonstrates the induction of peroxisome proliferation in rainbow trout administered ciprofibrate, a known peroxisome proliferator in rodents.

Acyl-CoA Oxidase↗
PubMed1990

Preliminary adult soil ingestion estimates: results of a pilot study.

Six adults were evaluated for the extent to which they ingest soil. This study was originally part of a large childhood soil ingestion study and was used to validate part of the analytical methodology used in that larger study. The adult study followed the soil tracer methodology of the children's study. The principal findings of the adult study revealed that the four most reliable tracer elements based on recovery studies in a mass balance assessment [aluminum (Al), silicon (Si), yttrium (Y), and zirconium (Zr)] yielded the following mean daily adult soil ingestion estimations: Al (77 mg), Si (5 mg), Y (53 mg), and Zr (22 mg). The median daily soil ingestion estimations based on these same tracer elements were: Al (57 mg), Si (1 mg), Y (65 mg), and Zr (-4 mg). These findings represent the first published quantitative estimates of soil ingestion by adults.

Adult↗