bluuebunny/crossref_metadata_2025 huggingface dataset:
The activity of erythrocyte enzymes and basic indices of peripheral blood erythrocytes from workers chronically exposed to mercury vapours
Authors: Zabiński Zbigniew , Dabrowski Zbigniew , Moszczyński Paulin , Rutowski Jan
Published: January 2007

The influence of occupational exposure to mercury vapours on the activity of the red cell enzymes [glucose-6-phosphate dehydrogenase (G-6PD), acetylcholinesterase (AChE), glutathione reductase (GR) and superoxide dismutase (SOD)], as well as on peripheral blood indices [erythrocyte number (RBC), HCT, Hb, MCHC] and on serum concentrations of iron, ferritin, transferrin and total iron binding capacity (TIBC), was assessed. Studies were carried out on 46 men aged between 21 and 56 years ( X=39±10.4) exposed to mercury vapours during their work from 7 months to 32 years (=14.7±10.8). The control group consisted of 35 healthy workers aged between 20 and 54 years ( X=33.6±9.8) not exposed to chemical nor physical agents. In both groups studied, there were 50% and 34.3% smokers, respectively. The activity of studied red cell enzymes—G-6PD, AChE, GR and SOD—was estimated according to the colorimetric methods described by Beutler and expressed as international units per gram of hemoglobin (IU g Hb−1). Peripheral blood cell parameters were determined using an automatic cell counter. The concentration of serum iron and TIBC was determined using colorimetric methods (Beckman), while that of ferritin and transferrin by nephelometric methods. The time-weighted average (TWA) of mercury concentration in the air determined before the study was 0.0028 mg m−3. Statistical analysis of the data was performed using either the Cochran and Cox C-test or the Student's t-test. The medium mercury concentration in the urine was 77.44±48.15 μg 1−1. In the group exposed to mercury vapours, a significant decrease was found in G-6PD activity (23.9%, P<0.001), GR (18.8%, P<0.001), and SOD (5%, P<0.001) with a concomitant increase in AChE activity (35.9%, P<0.001) was found. Moreover, a statistically significant increase occurred in HCT and RBC, and a decrease in MCV and MCHC as well as increases of ferritin (130.9%, P<0.001), transferrin (118.4%, P<0.001) and TIBC (11.2%, P<0.05). Our results indicate that long-term exposure to mercury vapours induces changes in the activity of red cell enzymes—G-6PD, AChE, GR and SOD—and may also influence other important hematological parameters of the peripheral blood.
Atsdr Evaluation of Health Effects of Chemicals. VII: Chlorinated Dibenzo-P-Dioxins
Authors: Pohl Hana R. , Llados Fernando , Ingerman Lisa , Cunningham Patricia , Raymer James H. , Wall Constance , Gasiewicz Thomas , De Rosa Christopher T.
Published: January 2007

As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of the most important parts of the Toxicological Profile for Chlorinated Dibenzo- p-dioxins (CDDs) [ATSDR. Toxicological profile for chlorinated dibenzo-dioxins (CDDs). Agency for Toxic Substances and Disease Registry, Atlanta, GA, 1998] into the scientific literature. Toxicological information includes health effects, toxicokinetics, mechanism of toxicity, biomarkers, interactions, and evaluation of animal to human extrapolation of data. Environmental information encompasses chemical and physical properties, potential for human exposure, and a listing of regulations and advisories. Because of the enormous database for CDDs, this particular toxicological profile is unusually long. Therefore, the profile had to be substantially shortened for the purpose of this article. Interested readers are encouraged to consult the original toxicological profile for more information. All original profiles can be requested from ATSDR's Information Center by telephone (1-888-42-ATSDR [1-888-422-8731] or E-mail: (atsdric@cdc.gov).
Effects of metal working fluids on B6C3F1 mouse skin
Authors: Al-Humadi Nabil H. , Battelli Lori , Willard Patsy A. , Schwegler-Berry Diane , Castranova Vincent , Kommineni Choudari
Published: January 2007

Over 10 million workers in the United States are exposed to metal working fluids (MWFs) through dermal contact and/or inhalation of aerosolized fluids. The objective of this study was to elucidate the response of skin to dermal exposure to MWFs. Four-to six-week-old B6C3F1 mice of both sexes were divided into eight groups ( n=5/group) and exposed to 200 μ1 of 0%, 5% (pH 7 and 9.7) and 100% (pH 10.4), unused MWFs/H2O by topical application to the unshaven back (cervical to sacral region), twice a week for 6 weeks. Skin-mast cell number in females of most treated groups and of two male groups (100% and 5%, pH 7) were significantly higher than the control groups. Eventhough both males and females (treated with 100% MWF/H2O) showed an increase in the skin-histamine levels (38% and 41%, respectively), this increase was significant in females only (ANOVA, P≤0.05). Dermal exposure to 100% MWFs increased liver weight significantly in both sexes. Ulcers and associated inflammation were seen in the skin of mice treated with 100% unused MWFs and sacrificed at 6 weeks, but not in the recovery groups. Hypertrophy of the sebaceous gland epithelium is present in all mice treated for 6 weeks and sacrificed immediately. However, only the mice treated with 100% MWF retained the hypertrophy of this epithelium after a 6-week recovery period. In conclusion, dermal exposure to unused semi-synthetic MWF penetrates the normal skin, induces mast cell accumulation in the skin, produces hypertrophy of the sebaceous glands, and may affect females more than males.
Liver adenomas and carcinomas: correlations and relationship to body weight in long-term rodent cancer bioassays
Authors: Gray George M. , Linkov Igor , Polkanov Michael , Wilson Richard
Published: January 2007

The most common cancers induced in laboratory rodents are liver cancers—both adenomas and carcinomas. There has been a long argument about the relative merits of combining them or considering them separately in the interpretation of long-term bioassays for chemical carcinogenesis. In this paper, we examine various aspects of the liver adenomas and liver carcinomas as seen in the Carcinogenesis Bioassay Data System (CBDS) and Toxicology Database Management System (TDMS) databases of the National Toxicology Program (NTP). It appears that the data themselves demonstrate interesting differences between the behavior of these tumors that probably have biological origin. Specifically, we find a strong negative correlation between the appearance of adenomas and carcinomas in the same animal in both control and chemically treated groups. This relationship does not seem to result from differential survival but may be influenced by the animal's body weight. Our analysis is generally consistent with either a progression of tumors from adenoma to carcinoma or a pathologist bias (that when a carcinoma is discovered, other tumors are ignored) as possible explanations for the negative correlation. However there are some differences between male and female mice that are puzzling. While we recognize the scientific and policy reasons for combination of adenomas and carcinomas for calculations of carcinogenic potency and risk we hope that toxicologists and pathologists will be encouraged to preserve the pathological distinctiveness of the two tumor types when analyzing rodent bioassays.
Letter to the editor: comments on “The health effects of living near cement kilns; a symptom survey in Midlothian, Texas”
Authors: Pichette Janet L.
Published: January 2007

In an article published in Toxicology and Industrial Health, Volume 14, Number 6, pp. 829-842, Legator et al. present results of a symptom survey they conducted in the city of Midlothian, Texas. The Texas Natural Resource Conservation Commission (TNRCC) offers a commentary regarding the use of a symptom survey to evaluate the health status of the residents of Midlothian, and concerns regarding the limitations of the survey. The TNRCC was provided a unique opportunity to review the data collected during the survey and to participate in the oral deposition of Dr. Marvin Legator, the principal investigator, who discussed the results during a deposition related to an administrative hearing regarding permitting one of the three operating cement companies in Midlothian. The TNRCC is able to offer a perspective of this symptom survey that may not be apparent to the casual reader or peer reviewer. There are numerous issues that the TNRCC has identified in their review of the authors' symptom survey; however, we limit our commentary to issues that are the most salient.
Urinalysis of atrazine exposure in farm pesticide applicators
Authors: Perry Melissa J. , Christiani David C. , Mathew John , Degenhardt David , Tortorelli James , Strauss John , Sonzogni William C.
Published: January 2007

This study compared three relatively common laboratory methods for the detection of atrazine (a triazine herbicide commonly used in US agriculture), and related metabolites in urine. Ninety-nine samples collected from atrazine applicators within 8 h post application were analyzed. Thirty-seven percent of applicators showed detectable levels (minimum=1.0 ng/ml) of deethylatrazine (an atrazine metabolite typically found in environmental samples) in their urine, based on gas chromatography-mass spectrometry (GC-MS) analysis (mean=14.2 ng/ml). Fifty applicator samples were tested using an enzyme-linked immunosorbent assay (ELISA) designed for the mercapturate metabolic product. Most of these samples (80%) had detectable levels of the mercapturate product. A triazine in water ELISAwas also used to test several diluted urine samples from atrazine applicators, and all samples were positive for triazines. Mediocre agreements between the three methods indicated that each detected distinct atrazine exposure products. The results indicate that single field applications of atrazine result in measurable pesticide doses to applicators and that the choice of field assay should depend on the exposure product to be evaluated.
Vitamin A physiology and its application as a biomarker of contaminant-related toxicity in marine mammals: a review
Authors: Simms Wendy , Ross Peter S.
Published: January 2007

In recent decades, marine mammal populations living in highly polluted areas have experienced incidences of low reproductive success, developmental abnormalities and disease outbreaks. In many of these cases, environmental contaminants were suspected as causal or contributing factors. However, demonstrating a mechanistic link between contaminant exposure and effect in marine mammal populations has proven challenging. Consequently, the development and application of relatively noninvasive biomarkers represents a potentially valuable means of monitoring wildlife populations exposed to elevated levels of contaminants. One touted biomarker is vitamin A (retinol), a “dietary hormone” whose metabolites are required for reproduction, growth, development, immune function, vision and epithelial maintenance. Laboratory studies have shown that many contaminants, including polychlorinated biphenyls (PCBs), polychlorinated dibenzo- para-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), can disrupt vitamin A physiology and alter the distribution of its essential metabolites. Field studies suggest that complex environmental mixtures of these chemicals can also interfere with vitamin A dynamics in free-ranging marine mammals and other fish-eating wildlife. However, circulatory retinol, which is the least invasive measurement of vitamin A status, appears to have variable responses to contaminant exposure. In addition, “normal” circulatory retinol levels have not yet been described for most wildlife species, and not enough is known about the natural physiological events that can alter these concentrations. Confounding factors must therefore be characterized before retinoids can be used as an effective indicator of adverse health effects in marine mammals exposed to elevated levels of environmental contaminants.
Evaluation of toxicity of methyl tert-butyl ether (MTBE) on mouse spermatogenic cells in vitro
Authors: Li DM , Han XD
Published: January 2007

As a synthetic organic chemical, methyl tert-butyl ether (MTBE) is the most common fuel oxygenate. The increasing use of MTBE has raised concern over its safety. Previous studies in vivo revealed that MTBE could alter the male reproduction system. Therefore, the current experiments were designed to evaluate whether isolated mice spermatogenic cells in vitro were sensitive to exposure to MTBE at environmental levels, and to evaluate whether spermatogenic cells had undergone changes in morphologic, activity and viability parameters after exposure to MTBE. Spermatogenic cells in vitro were incubated with medium alone (control), 100 ppb, 10 ppm, 1000 ppm, 3000 ppm MTBE, respectively, for 6, 12, 18 h. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo liumbromide) assay, staining with fluorescein diacetate (FDA) and propidium iodide (PI), and flow cytometric analyses were used to assess MTBE toxicity on cells and DNA. The results showed that there were no significant differences between control and treatments of ≤ 1000 ppm MTBE at the same time point. Although 3000 ppm MTBE could exert toxic effects directly on spermatogenic cells, environmental levels of MTBE did not exert toxic effects on cultured spermatogenic cells.
Peripubertal exposure to the antiandrogenic fungicide, vinclozolin, delays puberty, inhibits the development of androgen-dependent tissues, and alters androgen receptor function in the male rat
Authors: Monosson Emily , Kelce William R. , Lambright Christy , Ostby Joseph , Gray L. Earl
Published: January 2007

Vinclozolin is a well-characterized antiandrogenic fungicide. It produces adverse effects when administered during sexual differentiation, and it alters reproductive function in adult male rats by acting as an androgen-antagonist. Two active metabolites of vinclozolin, M1 and M2, compete with natural androgens for the rat and human androgen receptors (ARs), an effect that blocks androgen-induced gene expression in vivo and in vitro. In addition to their effects during perinatal life, androgens play a key role in pubertal maturation in young males. In this regard, the present study was designed to examine the effects of peripubertal oral administration of vinclozolin (0, 10, 30, or 100 mg kg−1 day−1) on morphological landmarks of puberty, hormone levels, and sex accessory gland development in male rats. In addition, as binding of the M1 and M2 to AR alter the subcellular distribution of AR by inhibiting AR-DNA binding, we examined the effects of vinclozolin on AR distribution in the target cells after in vivo treatment. We also examined serum levels of vinclozolin, M1, and M2 in the treated males so that these could be related to the effects on the reproductive tract and AR distribution. Vinclozolin treatment delayed pubertal maturation (at 30 and 100 mg kg−1 day−1) and retarded sex accessory gland and epididymal growth. Serum luteinizing hormone (LH; significant at all dosage levels) and testosterone and 5α-androstane,3α,17β-diol (at 100 mg kg−1 day−1) levels were increased. Testis size and sperm production, however, were unaffected. It was apparent that these effects were concurrent with subtle alterations in the subcellular distribution of AR. In control animals, most AR were in the high salt cell fraction, apparently bound to the natural ligand and DNA. Vinclozolin treatment reduced the amount of AR in the high salt (bound to DNA) fraction and it increased AR levels in the low salt (inactive, not bound to DNA) fraction. M1 and M2 were found in the serum of animals from the two highest dosage groups, but they were present at levels well below their Ki values. In summary, these results suggest that when the vinclozolin metabolites occupy a small percentage of AR in the cell, this prevents maximal AR-DNA binding and alters in vivo androgen-dependent gene expression and protein synthesis, which in turn results in obvious alterations of morphological development and serum hormone levels. It is noteworthy that similar exposures during prenatal life result in a high incidence of malformations in male rats.
Immunotoxicity of pesticides: a review
Authors: Blakley Barry , Brousseau Pauline , Fournier Michel , Voccia Isabelle
Published: January 2007

The intricate balance that is the hallmark of the immune system shows vulnerability to any chemical, including pesticides, that can cause structural and functional alterations to the system. The immunotoxic effects of xenobiotics include: histopathologic effects in immune tissues and organs; cellular pathology; altered maturation of immunocompetent cells; changes in B and T cell subpopulations; and functional alterations of immunocompetent cells. Pesticides, including fungicides, herbicides, and insecticides, are the only class of chemicals deliberately released into the environment because of their toxicity. Around the world, millions of people are exposed to pesticides at work and/or in their home. This article reviews evidence, from animal and human studies, on the effects of pesticides on the immune system.
Endocrine, immune, and behavioral effects of aldicarb (carbamate), atrazine (triazine) and nitrate (fertilizer) mixtures at groundwater concentrations
Authors: Jaeger James W. , Carlson Ian H. , Porter Warren P.
Published: January 2007

This paper describes the results of 5 years of research on interactive effects of mixtures of aldicarb, atrazine, and nitrate on endocrine, immune, and nervous system function. The concentrations of chemicals used were the same order of magnitude as current maximum contaminant levels (MCLs) for all three compounds. Such levels occur in groundwater across the United States. Dosing was through voluntary consumption of drinking water. We used fractional and full factorial designs with center replicates to determine multifactor effects. We used chronic doses in experiments that varied in duration from 22 to 103 days. We tested for changes in thyroid hormone levels, ability to make antibodies to foreign proteins, and aggression in wild deer mice, Peromyscus maniculatus, and white outbred Swiss Webster mice, Mus musculus, ND4 strain. Endocrine, immune, and behavior changes occurred due to doses of mixtures, but rarely due to single compounds at the same concentrations. Immune assay data suggest the possibility of seasonal effects at low doses. We present a multiple-level model to help interpret the data in the context of human health and biological conservation concerns. We discuss six testing deficiencies of currently registered pesticides, and suggest areas of human health concerns if present trends in pesticide use continue.
Herbicides and adjuvants: an evolving view
Authors: Burroughs B. , Tarone R. , Kesner J. S. , Garry V. F.
Published: January 2007

The present report examines the in vitro genotoxicity (micronucleus assay) of herbicides and adjuvants and reports on an in vivo human study on potential endocrine effects of pesticides, including herbicides. Adjuvants are used in conjunction with 2,4-dichlorophenoxy acetic acid (2,4-D) and other herbicides. Earlier pesticide applier survey results ( n = 709) show that 59% of the applicators used adjuvants, and the majority of this group used paraffinic oils and/or surfactant mixtures. As a beginning effort to explore the role of adjuvants and herbicides in hormonally based reproductive effects, a prospective, controlled study was performed to analyze blood specimens from three different exposure groups (applicators using herbicides only; applicators using both herbicides and insecticides; and applicators using fumigants in addition to herbicides and insecticides; and a control group composed of other agricultural workers including organic farmers). The applicators and controls were age- and smoking-matched. Study subjects ( n = 78) were tested before, during, and after completion of pesticide application season for the effects of pesticide products on hormone levels in the bloodstream. Of the applicator exposure groups examined, only the herbicide group showed significant endocrinologic differences from controls. Free testosterone levels were significantly elevated in post-season measurements ( p = 0.032), and follicle-stimulating hormone (FSH) was significantly decreased at the height of the season ( p = 0.016) and in the post-season ( p = 0.010) as compared to controls. These endocrinologic findings are discussed in terms of their possible relationship to potential endocrine effects of herbicides, herbicide contaminants, and adjuvants. In vitro genotoxicity examination compared four different commercially available surfactant mixtures with 12 different commercial herbicide products, including six different chlorophenoxy herbicides. Only one herbicide yielded a significant dose-response curve. All four adjuvants showed positive dose-response effects. These preliminary data suggest that adjuvants are not inert but are toxicologically active components added to herbicide mixtures. Whether adjuvant toxicant effects are additive or are independent of herbicide effects is poorly understood.
Dieldrin reduces male production and sex ratio in Daphnia galeata mendotae
Authors: Merritt Christine M. , Torrentera Laura , Winter Katherine M. , Tornehl Christopher K. , Girvin Kristin , Dodson Stanley I.
Published: January 2007

We used the sex ratio of neonate Daphnia, as well as the more standard endpoints of adult survivorship and fecundity and neonatal morphology, as an assay for detecting the effects of the insecticides endosulfan and dieldrin. Dieldrin caused a decrease in sex ratio (number of males/number of males plus females); we observed no endosulfan effect. We estimated (by extrapolation) that the sex ratio was reduced by dieldrin from concentrations of about 30 ppb and higher, based on a linear decrease in sex ratio with log dieldrin concentrations from 50 to 600 ppb. Neither insecticide significantly affected adult survival or clutch size. Because sex ratio changed but total neonate production did not change, the data suggest that the effect of dieldrin was on the sex-determining system during embryogenesis. Neither insecticide caused morphological abnormalities. Mixtures of the two pesticides produced only additive effects.
Pesticide use in the U.S. and policy implications: A focus on herbicides
Authors: Colborn Theo , Short Polly
Published: January 2007

This article examines herbicide use in the United States, providing estimates of poundage, land surface covered, distribution, and recent trends based on federal and state figures. Herbicides are by far the most widely used class of pesticide in the US, where 556 million lbs of herbicide active ingredients (AIs) were applied in 1995. Agriculture accounts for the majority of herbicide use, totaling 461 million lbs of AIs in 1995. Over 60% of the poundage of all agricultural herbicides consist of those that are capable of disrupting the endocrine and/or reproductive systems of animals. In addition, at least 17 types of `inert ingredients,' which can equal 90% or more of a pesticide product, have been identified as having potential endocrine-disrupting effects. Atrazine is the predominant herbicide used according to poundage, with 68-73 million lbs of AIs applied in 1995. However, 2,4-D is the most widespread herbicide, covering 78 million acres for agricultural uses alone. Both of these herbicides are reported endocrine disruptors. Acetolactate synthase (ALS) inhibitors, namely the sulfonylureas and imidazolinones, are one of the fastest growing classes of herbicides. Many of these herbicides are 100 times more toxic to select plant species than their predecessors, so they can be applied at rates approximately 100 times lower. Consequently, they can affect plant species at concentration levels so low that no standard chemical protocol can detect them. Due in part to these more potent herbicides, the poundage of herbicides used in the US has decreased since the mid-1980s; however, the available data suggest that the number of treated acres has not significantly declined. A thorough assessment of potential exposure to herbicides by wildlife and humans is limited due to the inaccessibility of production and usage data.
EEG sensitization during chemical exposure in women with and without chemical sensitivity of unknown etiology
Authors: Fernandez Mercedes , Bell Iris R. , Schwartz Gary E.R.
Published: January 2007

This study tested the sensitization model proposed by Bell et al. [Bell I.R., Miller C.S. and Schwartz G.E. An olfactory-limbic model of multiple chemical sensitivity syndrome: possible relationship to kindling and affective spectrum disorders. Biol. Psychiatry 1992:32:218-242] to study chemical sensitivity. The sensitization model indicates that a pharmacological stimulus or a traumatic event which elicits a strong response can sensitize limbic and/or mesolimbic pathways; and subsequent less intense trauma or stimuli, in the same or different modality, can elicit an amplified response. Three groups of subjects were tested: (1) women who reported chemical sensitivity and no sexual abuse (chemically sensitive, CS); (2) sexually abused (SA) women without chemical sensitivity; and (3) healthy women without chemical sensitivity or sensitivity or sexual abuse history (normal, N). All subjects were exposed to odorant and nonodorous control stimuli once a week for 3 weeks. Electroencephalographic activity was recorded while subjects sniffed the odorant and control stimuli. Results of the study revealed that both the CS and the SA group showed electroencephalogram (EEG) α sensitization across experimental sessions, while the N group showed little change over time. Additionally, EEG findings revealed that the CS group generated significantly greater α activity than the other two groups. Finally, while the groups were different on measures of psychological distress, these differences did not diminish the EEG findings. In summary, these findings suggest that intermittent exposure to chemicals elicits sensitization in CS and SA women without chemical sensitivity, supporting our expectations that chemical sensitivity is, in part, a manifestation of time-dependent sensitization (TDS). Additionally, these EEG findings indicate that CS women are unlike SA and healthy women in the amount of EEG α activity they generate. Finally, these findings indicate that psychological factors as assessed in this study do not explain electrophysiological differences between chemically and non-chemically-sensitive women.
Multiple chemical sensitivity as a conditional response
Authors: Siegel Shepard
Published: January 2007

Pavlovian conditioning may contribute to some cases of multiple chemical sensitivity (MCS). On the basis of the conditioning analysis, environmental stimuli (especially olfactory cues) present at the time of a toxicant overdose become associated with the toxicant and elicit aversive conditional responses. Similar associations have been reported in patients receiving chemotherapy, and the literature on such `pretreatment nausea' in cancer patients is relevant to understanding the role of conditioning in MCS. Evaluation of the contribution of conditioning to MCS has been complicated by confounding interpretations that emphasize conditional responses with interpretations which emphasize the psychiatric status of the patient. Appreciation of the contribution of Pavlovian conditioning to MCS will lead to a better understanding of this complex disorder.
Sensory irritation and multiple chemical sensitivity
Authors: Anderson Crosalind C. , Anderson Julius H.
Published: January 2007

Many of the symptoms described in Sick Building Syndrome (SBS) and multiple chemical sensitivity (MCS) resemble the symptoms known to be elicited by airborne irritant chemicals. Irritation of the eye, nose, and throat is common to SBS, MCS, and sensory irritation (SI). Difficulty of breathing is often seen with SBS, MCS, and pulmonary irritation (PI). We therefore asked the question: can indoor air pollutants cause SI and/or PI? In laboratory testing in which mice breathed the dilute volatile emissions of air fresheners, fabric softeners, colognes, and mattresses for 1 h, we measured various combinations of SI and PI as well as airflow decreases (analogous to asthma attacks). Air samples taken from sites associated with repeated human complaints of poor air quality also caused SI, PI, and airflow limitation (AFL) in the mice. In previous publications, we have documented numerous behavior changes in mice (which we formally studied with a functional observational battery) after exposure to product emissions or complaint site air; neurological complaints are a prominent part of SBS and MCS. All together, these data suggest that many symptoms of SBS and MCS can be described as SI, PI, AFL, and neurotoxicity. All these problems can be caused by airborne irritant chemicals such as those emitted by common commercial products and found in polluted indoor air. With some chemical mixtures (e.g., emissions of some fabric softeners, disposable diapers, and vinyl mattress covers) but not others (e.g., emissions of a solid air freshener), the SI response became larger (2- to 4-fold) when we administered a series of two or three 1-h exposures over a 24-h period. Since with each exposure the intensity of the stimulus was constant yet the magnitude of the response increased, we concluded that there was a change in the sensitivity of the mice to these chemicals. The response was not a generalized stress response because it occurred with only some mixtures of irritants and not others; it is a specific response to certain mixtures of airborne chemicals. This is one of the few times in MCS research that one can actually measure both the intensity of the stimulus and the magnitude of the response and thus be allowed to discuss sensitivity changes. The changing SI response of the mice might serve as a model of how people develop increasing sensitivity to environmental pollutants. Intensive study of this system should teach us much about how people respond to and change sensitivity to airborne irritant chemicals.
A rat model of neurobehavioral sensitization to toluene
Authors: Rogers Walter R. , Miller Claudia S. , Bunegin Leonid
Published: January 2007

Some individuals report that, following either a single high-level or repeated lower-level exposures to chemicals (initiation), subsequent exposure to very low concentrations of chemicals (triggering) produces a variety of adverse effects, including disruption of cognitive processes. Our objective was to model this two-step process in a laboratory animal. Two groups of 16 rats, eight male and eight female, received whole-body inhalation exposure to toluene, either at 80 ppm for 6 h/day for 4 weeks (Repeat group) or to 1600 ppm for 6 h/day on one day only (Acute group). Two other groups (Trigger group and Clean group) of 16 were sham-exposed. After 17 days without toluene exposure, the Acute, Repeat and Trigger groups began a series of daily toluene `trigger' exposures (10 ppm for 1 h) followed immediately by testing on an operant repeated-acquisitions task requiring learning within and across sessions. The Clean group was sham-exposed prior to operant testing. Trigger or sham exposures and operant testing continued 5 days/week for 17 sessions. Analysis of variance revealed a variety of statistically significant ( P<0.05) differences between treatment groups. Furthermore, the patterns of differences between groups differed ( P<0.05) for female and male rats. For example, male rats of the Trigger group made the most responses, and female rats of the Repeat group responded most slowly. The observation of important changes in the operant behavior of female and male rats previously exposed to toluene, at relatively low concentrations (80 or 1600 ppm) and then later re-exposed at very low concentrations (10 ppm), is consistent with the experiences of humans reporting cognitive difficulties following acute or chronic exposures to chemicals.
Low-level chemical sensitivity: implications for research and social policy
Authors: Ashford Nicholas A.
Published: January 2007

There is increasing evidence that human exposure to levels of chemicals once thought to be safe—or presenting insignificant risk—are, in fact, harmful. So-called low-level exposures are now known to be associated with adverse biological effects including cancer, endocrine disruption, and chemical sensitivity. This requires that we change both (1) the way we design research linking chemicals and health, and (2) the solutions we devise to address chemically caused injury. The new and emerging science of low-level exposure to chemicals requires appropriate social policy responses which include regulation of toxic substances, notification of those exposed, and compensation and reasonable accommodation to those affected. Research and social policy need to be focused towards two distinct groups: (1) those individuals who could become chemically intolerant as a result of an initiating exposure, and (2) those individuals who have already become chemically intolerant and are now sensitive to chemicals at low levels.
Functional alterations of alveolar macrophages subjected to smoke exposure and antioxidant lazaroids
Authors: Wang Shengjun , Lantz R. Clark , Vermeulen Mary W. , Chen Guan Jie , Breceda Veronica , Robledo Raymond F. , Hays Allison M. , Young Scott , Witten Mark L.
Published: January 2007

Acute inhalation of diesel fuel-polycarbonate plastic (DFPP) smoke causes severe lung injury, leading to acute respiratory distress syndrome (ARDS) and death. It has been reported that the initiation of acute lung injury is associated with the activation of pulmonary alveolar macrophages (PAM). To further explore the pathogenesis, alveolar macrophages (AM) of New Zealand rabbits ventilated and exposed to a 60 tidal volume of DFPP smoke in vivo were recovered at 1 h post-smoke. Smoke exposure induced significant increases in both mRNA and protein levels for PAM tumor necrosis factor-α (TNF-α), when compared to smoke control. Smoke also induced a biphasic response (inhibited at 2 h, enhanced at 24 h after cell isolation) in the production of superoxide (O2−) by PAM. However, aerosolized lazaroid, U75412E (1.6 mg/kg body weight), significantly attenuated smoke-induced expression in AM TNF-α at the protein level but not at the mRNA level, and smoke-induced changes in AM production of O2−. This study suggests that highly expressing AM TNF-α following smoke may be a key contributor to the cascade that establishes an acute injury process and exacerbates oxidant-derived cell injury. Whereas, the lazaroid may ameliorate smoke-induced lung injury by attenuating AM TNF-α release, in addition to its primary antioxidative mechanism.
Site-specific consultation for a chemical mixture
Authors: Pohl H. R. , Roney N. , Fay M. , Chou C.-H. S.J. , Wilbur S. , Holler J.
Published: January 2007

The Agency for Toxic Substances and Disease Registry (ATSDR) uses the weight of evidence methodology to evaluate interactions of chemical mixtures. In the process, toxicity, toxicokinetics, and toxicodynamics of chemical components of the mixture are carefully examined. Based on the evaluation, predictions are made that can be used in real-life situations at hazardous waste sites. In this paper, health outcomes were evaluated for a mixture of eight compounds that were found at a specific site. These eight chemicals were identified and possibly associated with human exposure. The health assessors could consider similar thought processes when evaluating chemical mixtures at hazardous waste sites.
Links between multiple chemical sensitivity and asthma in a rat model of cholinergic hypersensitivity: a brief review
Authors: Overstreet David H. , Djuric Veljko
Published: January 2007

Individuals with multiple chemical sensitivity (MCS) also commonly report symptoms of asthma, but, as far as we have been able to determine, no one has yet suggested that an abnormal cholinergic system may provide the link between asthma and MCS. The present brief review provides evidence for such a link by summarizing recent findings in a genetic animal model of cholinergic hyperresponsiveness. The Flinders Sensitive Line (FSL) rats were developed by selective breeding for increased responses to an anticholinesterase agent similar to commonly used organophosphate pesticides. Relative to their control line, the Flinders Resistant Line (FRL) rats, the FSL rats are more sensitive to drugs that stimulate acetylcholine receptors, alcohol, diazepam, and drugs that have a selective effect on dopamine or serotonin receptors. These findings raise the possibility that the FSL rats may resemble individuals with MCS. Hyperresponsiveness of the airways is a hallmark of asthma. The procedure known as whole-body plethysmography, where breathing can be monitored in freely moving animals, was employed to study the FSL and FRL rats. The FSL rats exhibited a greater index of bronchoconstriction than the FRL rats in response to both a cholinergic agonist and an allergen challenge. Thus, the FSL rats are more sensitive both to a variety of drugs unrelated to the cholinergic system and to cholinergic- and allergen-induced bronchoconstriction. An abnormal cholinergic system may therefore contribute to both MCS and asthma.
Subjective ratings of odorants by women with chemical sensitivity
Authors: Fernandez Mercedes , Schwartz Gary E.R. , Bell Iris R.
Published: January 2007

The purpose of the present study was to investigate whether women with chemical sensitivity rated the intensity and pleasantness of three odorants [peppermint, vanilla, and propylene glycol (PG)] and odorless room air differently than women without chemical sensitivity. The ratings of the experimental group (women with self-reported chemical sensitivity and no history of sexual abuse) were compared to those of two control groups who did not report chemical sensitivity [sexually abused (SA) women and healthy women without sexual abuse history]. All subjects were exposed to odorants and odorless control stimuli once a week for 3 consecutive weeks. Our findings indicate that women with chemical sensitivity perceive odorants as neither more or less intense nor more or less pleasant than women without chemical sensitivity. Moreover, the control women without sexual abuse outperformed the women in the other two groups by correctly identifying the target bottle containing the odorant. These findings suggest that perception of odorants alone is unlikely to account for the symptoms associated with chemical sensitivity. These findings, along with those of Doty et al. (1988), support the notion that olfactory-sensory function does not differ between individuals with and without chemical sensitivity.
Atsdr Evaluation Of Health Effects Of Chemicals. Vi. Di(2-Ethylhexyl)Phthalate.
Authors: Fay Mike , Donohue Joyce Morrissey , De Rosa Christopher
Published: January 2007

Di(2-ethylhexyl)phthalate (also known as DEHP, bis(2-ethylhexyl)phthalate, or BEHP; CAS Registry Number 117-81-7) is a widely-used plasticizer. It is found in numerous plastic articles, such as paints, inks, floor tiles, upholstery, shower curtains, footwear, plastic bags, food-packaging materials, toys, and medical tubing. Not surprisingly, DEHP appears at many waste sites. As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals that are of greatest public health concern at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priority List (NPL) sites. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of the bulk of ATSDR's profile for DEHP (ATSDR, 1993) into the mainstream scientific literature. An extensive listing of human and animal health effects, organized by route, duration, and endpoint, is presented. Toxicological information on toxicokinetics, biomarkers, interactions, sensitive subpopulations, reducing toxicity after exposure, and relevance to public health is also included. Environmental information encompasses physical properties, production and use, environmental fate, levels seen in the environment, analytical methods, and a listing of regulations. ATSDR, at the behest of Congress and therefore the citizenry, prepares these profiles to inform the public about site contaminants.
Docetaxel in hepatic impairment
Authors: Kolesar Jill M
Published: January 2007

Purpose. The primary objective of this paper is to provide a brief overview of docetaxel pharmacokinetics, pharmacodynamics, indications, and drug interactions, concentrating on their relationship with docetaxel use in patients with hepatic impairment.

Data Sources. The literature was reviewed through a MEDLINE search from 1986 to 2000. Relevant articles cited in literature obtained by MEDLINE searching were also considered. The following terms were searched: hepatic impairment, liver failure, Taxotere, and docetaxel. The search was restricted to the English language.

Data Extraction. The current literature is reviewed in regard to docetaxel pharmacokinetics, pharmacodynamics, dosing, efficacy, adverse effects, and drug interactions and with a special emphasis on docetaxel use in patients with hepatic impairment.

Data Synthesis. Docetaxel has a wide spectrum of clinical activity and is used frequently in the treatment of metastatic breast cancer, NSCLC, ovarian cancer and cancer of the head and neck. The dose-limiting toxicity of docetaxel is neutropenia. Docetaxel is metabolized in the liver and elevations in hepatic enzymes can predict a reduced clearance of docetaxel, which is associated with an increased incidence of neutropenia. Based on population pharmacokinetic modeling, docetaxel can be safely administered in patients with elevated hepatic enzymes if the dose is reduced on the first cycle.
Establishing a baseline incidence of adverse drug reactions in hospitalised oncology patients
Authors: Poole Susan Gaye , Dooley Michael Joseph
Published: January 2007

Objectives. To establish the incidence of adverse drug reactions (ADRs) in oncology patients hospitalised at a tertiary referral adult cancer hospital and identify areas where intervention strategies may effectively reduce their impact.

Design. A prospective study was conducted in November and December 1998 at the Peter MacCallum Cancer Institute (PMCI), Melbourne, Australia. Pharmacists identified patients who had experienced an ADR contributing to the admission or occurring during the episode of care.

Outcome measures. An assessment was made of causality, as definite, probably or possibly. The severity of the ADR was assessed as mild, moderate or severe.

Results. Twenty-six admissions (9.6%) were related to drug therapy. One hundred and thirty-four ADRs occurred in 86 inpatient episodes of care (31.6% of admissions). One hundred and four ADRs (60.8%) were associated with active therapy for malignancy or infection. Supportive therapy, including analgesics and antiemetics, were implicated in 67 (39.2%) adverse events. Pharmacists rated the majority of reactions as definitely associated with the implicated drug and the majority of at least moderate severity.

Discussion. Drug therapy contributed to 9.6% of admissions. This is higher than in other Australian studies. The majority of ADRs identified were associated with active therapy for malignancy or infection. These adverse effects are not unexpected in the setting of aggressive therapy. Other potentially preventable ADRs may be overlooked in the context of the more severe and life-threatening events occurring simultaneously.

Conclusion. Approximately 37.5% of patients admitted to PMCI experienced an ADR. Many of these events may have been prevented using simple intervention strategies. There is an opportunity for clinical pharmacists to ensure preventive measures are instituted, thereby improving patient outcomes.
The role of octreotide in symptom management in oncology and palliative care
Authors: Gilbar Peter J.
Published: January 2007

Objective. To provide an overview of the role of octreotide for managing symptoms in oncology and palliative care.

Data Sources. A search of MEDLINE and IDIS databases from 1985 to 1999 and CANCERLIT from 1993 to 1999 was conducted using the terms octreotide, cancer and palliative care. The reference lists from selected articles were also reviewed. Clinical trial databases on the Internet were searched. Oncology and palliative care textbooks were also used to obtain additional references.

Data Extraction. The retrieved literature was reviewed to discuss the pharmacology, pharmacokinetics, adverse effects, indications and principally, the clinical use of octreotide for controlling a number of symptoms encountered in the oncology and palliative care population.

Data Synthesis. The unique inhibitory activity of octreotide lends itself to many possible indications, including diarrhoea from a number of causes, bowel obstruction, nausea and vomiting, bleeding, death rattle, gastrointestinal fistulae, pain and hypercalcaemia. However, convincing pieces of evidence from large prospective clinical trials are required to realise its full potential in oncology and palliative care. Completed studies and clinical experience suggest that octreotide has a role in the treatment of a number of difficult-to-manage conditions, particularly bowel obstruction and diarrhoea due to disease or treatment-related causes. Proposed benefits of octreotide must be weighed against the possible adverse effects and cost effectiveness of treatment.
Docetaxel: use in non—small cell lung cancer and metastatic breast cancer and formulation update
Authors: Crown John , Palmby Wendy
Published: January 2007

Objective. To summarize the systematic development of docetaxel as a new and effective treatment option for advanced non-small cell lung cancer (NSCLC) and breast cancer patients, and to discuss the physical and chemical stability, compatibility with drugs commonly used in cancer patients, and administration issues with the new docetaxel formulation.

Data Sources. A MEDLINE search was conducted using carboplatin, cisplatin, compatibility, docetaxel, doxorubicin, metastatic breast cancer (MBC), NSCLC, and stability as search terms. Reference lists, bibliographies of pertinent articles, and abstracts from the American Society of Clinical Oncology and the European Society for Medical Oncology annual meetings were also identified and reviewed. Information related to the new docetaxel formulation was obtained from the manufacturer. The clinical literature was reviewed and analyzed.

Data Synthesis. Docetaxel has recently emerged as an active agent in the treatment of advanced NSCLC and MBC. Results of phase II and III studies of single-agent docetaxel and docetaxel combinations, both as first- and second-line therapy, have produced impressive response rates and improved survival times compared with current standards of care. Docetaxel has a unique toxicity profile that includes hypersensitivity reactions, skin toxicities, and fluid retention. Because docetaxel's toxicity profile differs from that of the platinum analogs and the anthracyclines, combinations with these agents for NSCLC and MBC are well tolerated.

Docetaxel was recently reformulated, allowing for improved stability, shelf-life, and storage requirements. Compatibility studies of docetaxel with 81 commonly used drugs in cancer patients were recently reported, showing that docetaxel is compatible with all but three drugs studied—amphotericin B, nalbuphine hydrochloride, and methylprednisolone sodium succinate—when administered as Y-site injections into existing intravenous lines. With the increasing use of this agent, the new docetaxel formulation and compatibility data should facilitate ease of administration.