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PubMed1995

Epiphyte size and taxonomy as biological indicators of ecological and toxicological factors in Lake Saint-François (Québec).

To assess the potential of the epiphyton community for monitoring spatial and temporal variations in the environmental quality of freshwater ecosystems, this paper describes the response of epiphytons to ecological and toxicological factors in Lake Saint-François, a fluvial lake of the St. Lawrence River (Québec). First, community descriptions and biotic indices based on size structure and on taxonomic composition were compared to test if size could usefully describe epiphyton response to environmental factors. Secondly, the relative contribution of ecological and toxicological variables in explaining the variation observed in epiphyton was quantified. A size-based approach classified the sites similarly to taxonomic analysis, but a larger portion of variance in size could be explained indicating a stronger relationship with environmental factors. Among both taxonomy and size-based biotic indices, the slope of the normalized size spectra performed best in terms of total explained variance. There were strong interactions between toxicological and ecological variables. These interactions should be considered in the planning and interpretation of biomonitoring studies. In such surveys, samples should be collected at sites with similar ecological characteristics: for example, the same macrophyte type and sediment texture. Interpretation of the data should consider the possible covariance of toxicological and ecological variables.

Journal Article↗
PubMed1996

Macroinvertebrate community as a biological indicator of ecological and toxicological factors in Lake Saint-François (Québec).

To assess the potential of the macroinvertebrate community for monitoring variation in the environmental quality of large rivers, the response of littoral macrobenthos in Lake Saint-François, a fluvial lake of the St Lawrence River (Québec) are described. First, the composition of total macroinvertebrate communities and important taxonomic groups as well as the biotic ICI-SL index in 16 littoral stations varying in sedimentology, water chemistry and contamination are described to define indicator species groups and environmental quality ranks. Thereafter, the relative contribution of ecological and toxicological factors in explaining the variation observed in macroinvertebrate assemblages and biotic index were quantified using partial canonical correspondence analysis. Cluster analyses based on taxonomic composition separated five groups of stations where macroinvertebrate assemblages varied in density, composition and tolerance to pollution. The ICI-SL biotic index varied from 7.2 to 27.2 with a mean value of 19 +/- 6. The ICI-SL values determined for the macroinvertebrate communities in Lake Saint-François did not reflect an important deterioration in environmental quality, and there was some agreement between the environmental quality ranking of the stations expressed either by the ICI-SL index or the community cluster analysis. Water conductivity and phosphorus concentration, followed by macrophyte types (Chara, Ceratophyllum) and sediment grain size, were the most significant ecological variables to explain variation in macroinvertebrate communities and derived ICI-SL index in Lake Saint-François. Among the toxicological factors, metals in water (Fe, Cr, Pb, Mn, Zn) and sediment (Mn, Pb, Se), as well as the composite indices of metal and organic contamination (water CI, sediment CI, sediment total PAHs) were the most important factors. The contamination factors selected in our models represented contaminant sorption processes rather than direct toxicological effects. The lack of clear relationships between contaminants and macroinvertebrate variables reflected the relative low level of contamination in the stations sampled in Lake Saint-François. There were some interactions between toxicological and ecological variables that should be considered in the planning of sampling and interpretation of biomonitoring studies. However, the large amount of unexplained variance (49.2-86.6%) in the CCA models underlined the limitations of the use of the indices of macroinvertebrate community structure that were assessed in this study for biomonitoring purposes in the absence of a contrasting pollution gradient.

Journal Article↗
PubMed2004

Toxicological resources for cumulative risk: an example with hazardous air pollutants.

Cumulative risk assessment, concerned with the multiple health effects of chemical mixtures, challenges the utility of existing single-chemical regulatory references. We compare example cumulative risk assessments for 40 HAPs; one based on single-effect toxicological data from EPA, and another based on a multiple-effect toxicological database we developed. For the 40-chemical HAP subset, the multiple effect database contains information on approximately seven effects per chemical and contains a total of 290 toxicological values. Seven health effects are represented in the IRIS data. Seventeen health effects are represented in the multiple-effect data. Respiratory and neurological effects ranked first and second in both cumulative analyses, regardless of the source data. In addition to respiratory and neurological effects, gastro-intestinal/hepatic, renal/kidney, and immunologic effects were identified as effects of concern on the basis of the multiple effect data. Immunologic effects are not found in the 40-chemical IRIS dataset. Cumulative risk assessment has the potential to expand our understanding of the public health impacts of environmental exposures. Advancements in toxicological resources will improve cumulative risk assessment. Cumulative risk assessment will reduce risks to the extent that it can be integrated into prevention strategies to track and protect the public's health.

Air Pollutants↗
PubMed2001

Could pesticide toxicology studies be more relevant to occupational risk assessment?

Pesticide toxicology study design has evolved from concern for oral exposure via food residues. The emphasis on the oral route does not generally apply to workers that are exposed primarily via the dermal route either handling pesticides or re-entering treated fields. As a result numerous assumptions about how oral toxicology results relate to dermal exposure must be made when conducting worker risk assessments. These assumptions introduce a high degree of uncertainty. Alternative toxicology study designs are suggested to reduce uncertainty when assessing risk. Because the dermal route is so important to characterizing occupational risk, methods to improve the accuracy of dermal absorption estimates are suggested, including the use of human subjects to study dermal absorption. Additional suggestions include tailoring dermal, oral and inhalation kinetic study designs to reflect worker exposure dosages. Suggestions are made to routinely conduct a single dose toxicity study patterned after the neurotoxicity study design to distinguish single dose effects and NOAELs from those resulting from multiple doses. Finally, interspecies pharmacokinetics studies are proposed to determine which toxicology study regimen of dosing best reflects intermittent worker exposure.

Administration, Inhalation↗
PubMed2002

Synthesis, beta-adrenoceptor pharmacology and toxicology of S-(-)-1-(4-(2-ethoxyethoxy)phenoxy)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethylamino)propane hydrochloride, a short acting beta(1)-specific antagonist.

The synthesis of S-(-)-1-(4-(2-ethoxyethoxy)phenoxy)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl)ethylamino)propane hydrochloride (D140S.HCl 6), a novel short acting beta(1)-specific adrenoceptor antagonist, has been described. The antagonist potency for D140S.HCl 6 has been compared with esmolol, another short acting agent, and other well known beta-adrenoceptor antagonists in isolated rat tissue preparations. The pharmacokinetics of D140S.HCl 6 in 7 day continuous intravenous infusions and 4 weeks intravenous bolus injection studies in conscious rats and dogs have been examined in toxicology studies. The effect on the isoprenaline-induced heart rate increase and the pharmacodynamic half-life of D140S.HCl 6 has been compared with esmolol in a conscious rat model. In addition, the results of a range of toxicological studies are presented. The results indicate that D140S.HCl 6 is a highly specific beta(1)-adrenoceptor antagonist (pA(2) = 8.15+/-0.22, beta(1)/beta(2) selectivity > 4400). The in vitro studies suggest D140S.HCl is ca. ten times more potent and 60 times more beta(1)-specific than racemic esmolol. Pharmacokinetic non-linearity was seen when given as a 7 day intravenous infusion at toxicological doses above 10 mg kg(-1) h(-1) in the rat and 2.5 mg kg(-1) h(-1) in the dog. Both D140S.HCl 6 and esmolol have very short durations of action after intravenous infusion in the rat (pharmacodynamic half-life is < 15 min for D140S.HCl and 10 min for esmolol). The toxicological tests indicate that D140S.HCl 6 shows no unexpected toxicity and none of the tissue irritancy problems reported for esmolol formulations.

Adrenergic beta-1 Receptor Agonists↗
PubMed1999

The substance abuse subtle screening inventory minimizes the need for toxicology screening of prenatal patients.

Multiple authors have reported attempts to effectively address the discovery of substance abuse in pregnancy using various mechanisms to encourage positive self-reports and urine toxicology to augment identification. In this study, we evaluated 1,251 patients with (a) self-report, (b) the Substance Abuse Subtle Screening Inventory (SASSI), and (c) urine toxicology screening to determine which modality or combination would yield the most cost-effective discovery. Combining the SASSI with the self-report was the most clinically effective and cost effective mode of discovery. This led to the development of a clinical protocol using the SASSI and self-report with limited use of urine toxicology for specific patient subgroups. Alcohol abuse, which is missed by toxicology and self-report, is detected by the SASSI.

Adult↗
PubMed1995

Molecular toxicology endpoints in rodent inhalation studies.

Although histopathology will continue to be essential for assessing the results of rodent inhalation studies, molecular toxicology endpoints are of increasing importance, as these techniques often complement and extend histopathological examinations. One of the primary uses of molecular toxicology is determining the delivered dose of the inhaled material to macromolecules in target tissues. During inhalation studies this is most often done by measuring DNA adducts in the respiratory tract. DNA adducts may be measured specifically (e.g. using monoclonal antibodies or mass spectrometry) or non-specifically (e.g. by using the 32P-post-labeling assay). Another major use of molecular toxicology techniques is the assessment of cellular and molecular changes in target tissues which may precede or be more sensitive than histopathologic alterations. For example, rates of cellular DNA synthesis occurring in target tissues may be quantified at any time during the study by administering the animals either radiolabelled thymidine or the non-radiolabelled thymidine analog bromodeoxyuridine (BrdU). Pulmonary changes may be assessed in bronchoalveolar lavage fluid using either cellular (e.g. macrophage number, granulocyte number) or biochemical (e.g. alkaline phosphatase, lactate dehydrogenase) techniques. The potential of the inhaled material to produce genetic alterations may be evaluated by examining the chromosomes of pulmonary alveolar macrophages for cytogenetic changes. To illustrate the use of these endpoints, an experiment was conducted to determine the molecular toxicology of aged and diluted sidestream smoke (a surrogate for environmental tobacco smoke) in rodent inhalation studies. The endpoints measured were DNA adducts in target and non-target tissue, chromosome aberrations in pulmonary alveolar macrophages, and DNA synthesis in the epithelial lining of the nasal turbinates.

Administration, Inhalation↗
PubMed2004

Review of the toxicology, human exposure and safety assessment for bisphenol A diglycidylether (BADGE).

BADGE (whose chemical names are bisphenol A diglycidylether and 2,2-bis(4-(2,3-epoxypropyl)phenyl)propane) is the lowest molecular weight oligomer in commercial epoxy resins and the major component in commercial liquid epoxy resins. The major application areas for epoxy resins are protective coatings and civil engineering. Additional applications include printed circuit boards, composites, adhesives and tooling, while a relatively small amount of epoxy resins (< 10%) finds use in protective coatings inside food and drink cans. The use of BADGE in food-contact applications was first regulated through EC Directive 2002/16/EC and amended in EC Directive 2004/13/EC with migration levels in food-contact applications being generally well below the regulatory thresholds. The paper discusses the commercial use of BADGE focusing on the current knowledge of human exposure from canned food applications. To assess the safety of this application, the exposure data are compared with no adverse effect levels (NOAEL) from various toxicological investigations with BADGE including reproductive and developmental assays, endocrine toxicity investigations, and sub-chronic and chronic assays. Consumer exposure to BADGE is almost exclusively from migration of BADGE from can coatings into food. Using a worst-case scenario that assumes BADGE migrates at the same level into all types of food, the estimated per capita daily intake for a 60-kg individual is approximately 0.16 microg kg(-1) body weight day(-1). A review of one- and two-generation reproduction studies and developmental investigations found no evidence of reproductive or endocrine toxicity, the upper ranges of dosing being determined by maternal toxicity. The lack of endocrine toxicity in the reproductive and developmental toxicological tests is supported by negative results from both in vivo and in vitro assays designed specifically to detect oestrogenic and androgenic properties of BADGE. An examination of data from sub-chronic and chronic toxicological studies support a NOAEL of 50 mg kg(-1) body weight day(-1) from the 90-day study, and a NOAEL of 15 mg kg(-1) body weight day(-1) (male rats) from the 2-year carcinogenicity study. Both NOAELS are considered appropriate for risk assessment. Comparing the estimated daily human intake of 0.16 microg kg(-1) body weight day(-1) with the NOAELS of 50 and 15 mg kg(-1) body weight day(-1) shows human exposure to BADGE from can coatings is between 250,000 and 100,000-fold lower than the NOAELs from the most sensitive toxicology tests. These large margins of safety together with lack of reproductive, developmental, endocrine and carcinogenic effects supports the continued use of BADGE for use in articles intended to come into contact with foodstuffs.

Animals↗
PubMed2007

Special-purpose fiber type 475--toxicological assessment.

Type 475 special-purpose glass fiber is rather unique among the family of synthetic mineral fibers. It is used not for insulation but for "high-end" filtration products designed for high and ultra-high purity filtration of air and liquids. The designation for these types of filters varies with country and includes HEPA, ULPA, EU 10-13, EN1822, and S3. In its evaluation, type 475 has been grouped together with E-glass another special-purpose fibre often with little distinction made in terms of its chemistry and corresponding toxicological response. The detailed review of the available toxicology data on type 475 glass fibers clearly shows that following inhalation of this fiber even at relatively high doses, which likely exceed that at which lung overload in the rat is known to occur, type 475 glass fibers are not fibrogenic and do not cause tumors. These data clearly show an important differentiation in potency between type 475 glass fibers and E-glass and support treating these two types of fibers independently and not equating them though the term "special-purpose fibers." Analysis of the intraperitoneal studies taking into account fibre dimensions shows that at 109 fibers injected, there was a 0.3 tumor incidence. While these studies indicate according to the European Commission (EC) classification criteria that 475 should not be fully exonerated as a carcinogen, the results of the inhalation study fully support classification in category 3. The IP results are more difficult to interpret, however, the IP study itself provides no toxicological basis for determining what range of dose-response should correspond to EU category 3 or 2. Following the EC classification criteria, the toxicological data clearly indicate that 475 fibers are appropriately classified in EC category 3.

Administration, Inhalation↗
PubMed1986

Food applications and the toxicological and nutritional implications of amorphous silicon dioxide.

The chemical and physical characteristics of the different types of amorphous silicon dioxide contribute to the versatility of these compounds in a variety of commercial applications. Traditionally, silicas have had a broad spectra of product usage including such areas as viscosity control agents in inks, paints, corrosion-resistant coatings, etc. and as excipients in pharmaceuticals and cosmetics. In the food industry, the most important application has been as an anticaking agent in powdered mixes, seasonings, and coffee whiteners. However, amorphous silica has multifunctional properties that would allow it to act as a viscosity control agent, emulsion stabilizer, suspension and dispersion agent, desiccant, etc. The utilization of silicas in these potential applications, however, has not been undertaken, partially because of the limited knowledge of their physiochemical interactions with other food components and partially due to their controversial status from a toxicological point of view. The main goal of this review is to compile current information on the incorporation of amorphous silicon dioxide as a highly functional and viable additive in the food processing industry as well as to discuss the most recent toxicological investigations of silica in an attempt to present some of the potential food applications and their concomitant toxicological implications. Some of the more significant differences between various silicas and their surface chemistries are presented to elucidate some of their mechanisms of interaction with food components and other biological systems and to aid in the prediction of their rheological or toxicological behavior.

Animals↗
PubMedDate not supplied

Applications of emerging technologies in toxicology and safety assessment.

Standardized protocols for repeat-dose toxicity studies have many advantages, including experimental redundancy (i.e., the use of more than a single experimental approach in the assessment of a given organ or tissue) and evaluation of numerous tissues to ensure detection of adverse effects, as well as the ability to develop robust historical control databases. However, traditional toxicology study designs may not adequately address questions of a mechanistic nature that might provide insights on whether particular toxicology findings in animals are relevant to humans. Such questions may be more readily answered using mechanism-based technologies such as toxicogenomics, proteomics, or metabonomics. Such newer approaches may permit, for example, the detailed assessment of the transcriptional profile differences that distinguish a normal healthy tissue from a diseased or damaged tissue. The resultant information can be used to elucidate the mechanism and accompanying biomarkers for toxicity, as well as to identify potential molecular targets for therapeutic intervention by drugs. Despite their conceptual appeal, the use of emerging technologies in toxicology is accompanied by significant challenges. For example, toxicogenomic assessments entail the generation of large amounts of bioinformatic data that must be interpretable for their full value to be realized. Also, none of these newer approaches have established uniformly acceptable quality standards (e.g., such as may be defined in interlaboratory validation studies) or a track record of achievement in guiding regulatory decisions. As a result, newer techniques, at least for the present, are more likely to be focused on mechanistic questions with compounds of known toxicity (either positive indicator compounds or "failed" pharmaceutical candidates). If the use of a nascent or emerging technology is contemplated for mechanistic studies of pharmaceutical compounds later in preregistration development, it will be crucial for toxicologists to engage their regulatory colleagues in discussions at an early stage to ensure closer alignment in thought. The successful use of emerging technologies to address toxicology issues will require a close partnership between industry and regulatory agencies.

Animals↗
PubMedDate not supplied

TaqMan applications in genetic and molecular toxicology.

Quantification of nucleic acids has become a common procedure in many toxicology laboratories. Among the technologies that accomplish this is the fluorogenic 5'-nuclease assay, commonly known as TaqMan. Three TaqMan applications for genetic and molecular toxicology are presented in this article: quantification of gene expression, detection of genetic polymorphisms, and quantification of chromosomal DNA deletions. Of these, quantification of gene expression is the most widely used, and established TaqMan as a benchmark technology for nucleic acid quantification. Two additional applications, polymorphism detection and quantification of DNA deletions, demonstrate the flexibility and quantitative strengths that make TaqMan so powerful, including high precision, excellent sensitivity, and broad linear dynamic range. These and similar applications improve our ability to investigate genetic and molecular dimensions of toxicological phenomena, and have promoted the widespread use of TaqMan in toxicology departments in the pharmaceutical industry. In addition to presenting these applications, the authors discuss some of the challenges of integrating TaqMan and other new technologies into the drug development process.

Animals↗
PubMedDate not supplied

Toxicology and immunotoxicology of mercury: a comparative review in fish and humans.

This review addresses an important area of environmental and mammalian toxicology by evaluating and comparing mercury-induced effects upon the immune responses of two evolutionarily divergent yet immunologically-related species. The mechanisms of mercury toxicology and immunotoxicology are described herein, including supporting data from the following: sources of exposure; bioavailability and biodistribution; metabolism; and laboratory and field investigations. Based upon the studies presented, the relative sensitivities of fish and human immune cells to mercury exposure are compared and contrasted with regard to mercury's ability to stimulate and/or suppress host immunocompetence. In addition, results from immune assays are compared to mercury tissue burdens, as well as to toxicological threshold level estimates. Such comparisons may help to resolve gaps in our knowledge regarding sensitivity of immunological assays, standardization of immunotoxicological techniques between species, and the extent to which the vertebrate immune system possesses functional reserve and redundancy in response to xenobiotics. A review of this type begins to provide support for the potential usefulness of fish immune cells to serve as indicators for human immunotoxicology risk assessment. Analysis of the reviewed studies supports the following conclusions in both lower and higher vertebrates: a threshold for mercury-induced immunotoxicological effects is likely; multiple exposure scenarios involving high and/or chronic exposures leading to increased body burdens are linked to increased risk of immunomodulation; and highly exposed and/or susceptible subpopulations are at greater risk of toxicological impact.

Animals↗
PubMed2002

A critical review of the toxicological effects of carrageenan and processed eucheuma seaweed on the gastrointestinal tract.

Carrageenan is a high-molecular-weight, strongly anionic polymer derived from several species of red seaweed that is used for the textural stabilization of foods. Processed Eucheuma Seaweed (PES) is a form of carrageenan with a higher cellulose content. Food-grade carrageenan has a weight average molecular weight greater than 100,000 Da, with a low percentage of smaller fragments. Carrageenan is not degraded to any extent in the gastrointestinal tract and is not absorbed from it in species examined, such as rodents, dogs, and non-human primates. Systemically administered carrageenan has been reported to have a variety of effects, particularly on the immune system, but these are not pertinent to orally administered carrageenan. The substance poligeenan (formerly referred to as degraded carrageenan) is not a food additive. It exhibits toxicological properties at high doses that do not occur with the food additive carrageenan. In-long term bioassays, carrageenan has not been found to be carcinogenic, and there is no credible evidence supporting a carcinogenic effect or a tumor-promoting effect on the colon in rodents. Also, like many dietary fibers, there is significant cecal enlargement in rodents when it is administered at high doses, but this does not appear to be associated with any toxicological consequences to the rodent. Many toxicological studies on carrageenan have involved administration at doses in excess of today's standards for dietary feeding levels in bioassays, and they are orders of magnitude in excess of those to which humans are exposed. Previous reviews of carrageenan and PES by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA) have recommended a group allowable daily intake (ADI) of "not specified". The lack of carcinogenic, genotoxic, or tumor-promoting activity with carrageenan strongly supports continuing such an ADI, and JECFA, during its most recent review in 2001, continued this recommendation. The various toxicological studies related to orally administered food-grade carrageenan are summarized along with a brief discussion of critical factors in intestinal carcinogenesis.

Administration, Oral↗
PubMed2002

Implementation of the 3Rs (refinement, reduction, and replacement): validation and regulatory acceptance considerations for alternative toxicological test methods.

Toxicological testing in the current regulatory environment is steeped in a history of using animals to answer questions about the safety of products to which humans are exposed. That history forms the basis for the testing strategies that have evolved to satisfy the needs of the regulatory bodies that render decisions that affect, for the most part, virtually all phases of premarket product development and evaluation and, to a lesser extent, postmarketing surveillance. Only relatively recently have the levels of awareness of, and responsiveness to, animal welfare issues reached current proportions. That paradigm shift, although sluggish, has nevertheless been progressive. New and alternative toxicological methods for hazard evaluation and risk assessment have now been adopted and are being viewed as a means to address those issues in a manner that considers humane treatment of animals yet maintains scientific credibility and preserves the goal of ensuring human safety. To facilitate this transition, regulatory agencies and regulated industry must work together toward improved approaches. They will need assurance that the methods will be reliable and the results comparable with, or better than, those derived from the current classical methods. That confidence will be a function of the scientific validation and resultant acceptance of any given method. In the United States, to fulfill this need, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and its operational center, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), have been constituted as prescribed in federal law. Under this mandate, ICCVAM has developed a process and established criteria for the scientific validation and regulatory acceptance of new and alternative methods. The role of ICCVAM in the validation and acceptance process and the criteria instituted toward that end are described. Also discussed are the participation of the US Food and Drug Administration (FDA) in the ICCVAM process and that agency's approach to the application and implementation of ICCVAM-recommended methods.

Animal Testing Alternatives↗
PubMed1999

Toxicology of protein allergenicity: prediction and characterization.

The ability of exogenous proteins to cause respiratory and gastrointestinal allergy, and sometimes systemic anaphylactic reactions, is well known. What is not clear however, are the properties that confer on proteins the ability to induce allergic sensitization. With an expansion in the use of enzymes for industrial applications and consumer products, and a substantial and growing investment in the development of transgenic crop plants that express novel proteins introduced from other sources, the issue of protein allergenicity has assumed considerable toxicological significance. There is a need now for methods that will allow the accurate identification and characterization of potential protein allergens and for estimation of relative potency as a first step towards risk assessment. To address some of these issues, and to review progress that has been made in the toxicological investigation of respiratory and gastrointestinal allergy induced by proteins, a workshop, entitled the Toxicology of Protein Allergenicity: Prediction and Characterization, was convened at the 37th Annual Conference of the Society of Toxicology in Seattle, Washington (1998). The subject of protein allergenicity is considered here in the context of presentations made at that workshop.

Allergens↗
PubMed2003

The hormetic dose-response model is more common than the threshold model in toxicology.

The threshold dose-response model is widely viewed as the most dominant model in toxicology. The present study was designed to test the validity of the threshold model by assessing the responses of doses below the toxicological NOAEL (no observed adverse effect level) in relationship to the control response (i.e., unexposed group). Nearly 1,800 doses below the NOAEL, from 664 dose-response relationships derived from a previously published database that satisfied a priori entry criteria, were evaluated. While the threshold model predicts a 1:1 ratio of responses "greater than" to "less than" the control response (i.e., a random distribution), a 2.5:1 ratio (i.e., 1171:464) was observed, reflecting 31% more responses above the control value than expected (p < 0.0001). The mean response (calculated as % control response) of doses below the NOAEL was 115.0% +/- 1.5 standard error of the mean (SEM). These findings challenge the long-standing belief in the primacy of the threshold model in toxicology (and other areas of biology involving dose-response relationships) and provide strong support for the hormetic-like biphasic dose-response model characterized by a low-dose stimulation and a high-dose inhibition. These findings may affect numerous aspects of toxicological and biological/biomedical research related to dose-response relationships, including study design, risk assessment, as well as chemotherapeutic strategies.

Animals↗
PubMed2003

Shrinking the biologic world--nanobiotechnologies for toxicology.

Although toxicologic effects need to be considered at the organismal level, the adverse events originate from interactions and alterations at the molecular level. Cellular structures and functions can be disrupted by modifications of the nanometer structure of critical molecules; therefore, devices used to assess biologic and toxicologic processes at the nanoscale will allow important new research pursuits. In order to properly assess alterations at these dimensions, nanofabricated tools are needed to detect, separate, analyze, and manipulate cells or biologic molecules of interest. The emergence of laser tweezers, surface plasmon resonance (SPR), laser capture microdissection (LCM), atomic force microscopy (AFM), and multi-photon microscopes have allowed for these assessments. Micro- and nanobiotechnologies will further advance biologic, clinical, and toxicologic endeavors with the aid of miniaturized, more sensitive devices. Miniaturized table-top laboratory equipment incorporating additional innovative technologies can lead to new advances, including micro total analysis systems (microTAS) or "lab-on-a-chip" and "sentinel sensor" devices. This review will highlight several devices, which have been made possible by techniques originating in the microelectronics industry. These devices can be used for toxicologic assessment of cellular structures and functions, such as cellular adhesion, signal transduction, motility, deformability, metabolism, and secretion.

Animals↗