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At least 757 records · Page 42Linked to original sources
PubMed1996

The use of toxic equivalency factors in assessing occupational and environmental health risk associated with exposure to airborne mixtures of polycyclic aromatic hydrocarbons (PAHs).

The health risk associated with inhalatory exposure to PAHs either in the occupational atmosphere or in outdoor air is commonly assessed on the basis of benzo(a)pyrene (BaP) concentrations in air. The PAH-related health risk is calculated with the help of epidemiological data from coke oven workers. The proportion of individual carcinogenic PAHs to BaP has been shown to vary in different environments by one to two orders of magnitude. Despite this, the unit risk value for BaP derived from epidemiological studies of coke oven workers is used for risk estimation of these environments. Toxic equivalency factors (TEFs) for individual PAHs were used to estimate human health risk associated with inhalatory exposure to PAHs. Given the uncertainties involved in risk assessment in general, a variability of risk estimation for PAH mixtures based on the toxic equivalency factor concept by a factor 2.6 is low and rather unreasonably precise. This underlines the importance of BaP as a surrogate compound of a PAH mixture.

Air Pollutants, Occupational↗
PubMed2004

Skin.

Human skin provides a barrier between the host and the physical, chemical, and biological environment. It is also a potential portal of entry for hazardous or infectious agents and a potential target of environmental toxins. Cutaneous vulnerability may take on many forms in the embryo, infant, child, and adolescent. Teratogenic agents may occasionally target skin, as appreciated in the proposed association of the antithyroid medication methimazole, with the congenital malformation known as aplasia cutis congenita. Percutaneous absorption of topically applied substances and the potential for resultant drug toxicities are important considerations in the child. Many topical agents have been associated with systemic toxicity, including alcohol, hexachlorophene, iodine-containing compounds, eutectic mixture of local anesthetics, and lindane. Percutaneous toxicity is of greatest concern in the premature infant, in whom immaturity of the epidermal permeability barrier results in disproportionately increased absorption. Immature drug metabolism capabilities may further contribute to the increased risk in this population. Ultraviolet (UV) radiation exposure, which increases an individual's risk of cutaneous carcinogenesis, may be a particularly significant risk factor when it occurs during childhood. The "critical period hypothesis" suggests that UV exposure early in life increases the risk of eventual development of malignant melanoma. Other risk factors for malignant melanoma may include severe sunburns during childhood, intense intermittent UV exposure, and increased susceptibility of pediatric melanocytes to UV-induced DNA damage. Last, percutaneous exposure to environmental toxins and chemicals, such as insecticides and polychlorinated biphenyls, may differ between children and adults for several reasons, including behavioral patterns, anatomic and physiologic variations, and developmental differences of vital organs.

Child↗
PubMed2003

Joint acute toxicity of diazinon and copper to Ceriodaphnia dubia.

Diazinon and copper are two contaminants that are widely found in urban streams and in municipal wastewater effluents. Because these contaminants may be found concurrently, the potential for their joint toxicity is of interest, particularly with regard to toxicity testing of wastewater effluents and the ecological implications of simultaneous exposures in urban streams. Although interactions between metals are well studied, relatively little is known about interactions between metals and organophosphate compounds such as diazinon. In this study, the interaction between copper and diazinon was evaluated using cladoceran (Ceriodaphnia dubia) in 48-h static tests within laboratory water. Using toxic units derived from concurrently established 48-h median lethal concentration values (LC50) of test organisms of each individual toxicant, the effects of the mixture of copper and diazinon on the survival of C. dubia were shown to be generally nonconcentration additive (LC50 significantly greater than one toxic unit). However, evaluation of the dose-response relationship across the entire range of effect levels revealed that the mortality induced by the mixture of copper and diazinon supported concentration additivity at higher effect levels.

Animals↗
PubMed2000

Immunosuppression in mice fed on diets containing beluga whale blubber from the St Lawrence estuary and the Arctic populations.

In order to assess the immunotoxic potential of naturally relevant mixtures of PCBs and other organohalogens, C57Bl/6 mice were fed on diets in which lipids were replaced by blubber of beluga whales from the highly contaminated population of the Saint-Lawrence River, and the less contaminated population from the Arctic. Different ratios of blubber from both sources were mixed in order to allow a dose-response study. Mice were fed for a period of 90 days at the end of which their immunological status was monitored. For general parameters such as body weight, weight of the spleen and the thymus no significant effect of diets were observed. The immunological endpoints such as the blastic transformation of splenocytes and the spleen NK cell activity were not significantly affected by any of the diets compared to control diets. While the different cell subpopulations of peripheral blood and thymus were not affected by the diets, a significant decrease was noted in the CD8+ T cell population in the spleen of mice fed with most of the diets containing beluga blubber. Moreover, the ability of splenic cells to elicit humoral response against sheep red blood cells as well as the potential of peritoneal macrophages to perform phagocytosis were suppressed by all diets containing beluga blubbers. In summary, there was no differences between the groups fed with a blubber diet with low and high organochlorine contamination. However, a clear immunosuppression was demonstrated when these groups were compared to the group fed with beef oil. Despite the fact that we cannot exclude a possible contribution of the fatty acid composition of the beluga blubber to the immunosupression, these results suggest the sensitivity of mouse immune system towards organohalogens, and point out the toxic potential of contaminant mixtures as found in the less contaminated Arctic population.

Adipose Tissue↗
PubMedDate not supplied

[Suppression of the human immunodeficiency virus in cultured cells by 5'-phosphites of 3'-azido-2',3'-dideoxynucleosides].

5'-Phosphites (5'-hydrogenphosphonates) of 3'-azido-2'-, 3'-dideoxynucleosides are shown to be effective inhibitors of the human immunodeficiency virus (HIV-1) in MT4 cell culture. 5'-Phosphite of 3'-azido-2', 3'-dideoxythymidine was the most active among these compounds and even a little more active as compared to the well-known anti-AIDS drug 3'-azido-2',3'-dideoxythymidine; at the same time 5'-phosphites of 3'-azido-2',3' -dideoxynucleosides with adenine, guanine and cytosine bases were more active than the corresponding nucleosides. The toxicity of all four phosphites was comparatively low and the equimolar mixture of all four phosphites was 2-3 fold less toxic than each of them separately. Data on the decreased toxicity of the phosphite mixture are explained from the viewpoint of a decreased pool disbalance of natural 2'-deoxynucleoside 5'-triphosphates in cells; a significant pool disbalance is developed in the case of 3'-azido-2',3'-dideoxythymidine action.

Antiviral Agents↗
PubMed2002

Development and application of an oil toxicity and exposure model, OilToxEx.

An oil toxicity and exposure model (OilToxEx) was developed and validated for estimation of impacts to aquatic organisms resulting from acute exposure to spilled oil. Because oil exposure is shorter than the time required for equilibrium between the organism and the water to be reached, the time and temperature dependence of toxicity is addressed. Oil toxicity is a function of aromatic composition and the toxicity of individual aromatics in the mixture. Lethal concentration to 50% of exposed organisms (LC50), as a function of octanol-water partition coefficient (Kow), and an additive model are used to estimate the toxicity of monoaromatic and polycyclic aromatic hydrocarbon mixtures in water-soluble fractions (WSF) and oil-in-water dispersions (OWD) of oil. The toxicity model was verified by comparison with oil bioassay data where the exposure concentrations of aromatics were measured. The observed toxicity in the bioassays could be accounted for by the additive narcotic effects of the dissolved aromatics in the exposure media. Predicted LC50s were compared to those calculated from measured concentrations after spills to verify the exposure model for field conditions. These results indicate that the additive toxicity and exposure model may be used to estimate toxicity of untested oils and spill conditions.

Environmental Exposure↗
PubMed1997

Site directed mutagenesis of histidine residues in anthrax toxin lethal factor binding domain reduces toxicity.

Anthrax lethal toxin is a mixture of protective antigen (PA, 735 AA) and lethal factor (LF, 776 AA). Earlier studies have shown that 254 residues of lethal factor are sufficient for PA binding to cause internalization (Arora N and Leppla SH, J Biol Chem 268: 3334-3342, 1993). The present study was undertaken to determine residues which are important for binding of LF to PA. LF modification with diethyl pyrocarbonate (DEPC, modifies histidine residue primarily) results in the loss of binding and toxicity in mammalian cells. There are nine histidine residues in the binding domain. To locate the important residue(s), site-directed mutagenesis of these histidines were performed by recombinant methods. Replacement of His42 with Gly42 destablizes the protein and hence it could not be purified. His35 when mutagenized to Gly35 (mLF-DTA) diminishes the toxicity by 20 fold. Time dependent studies show that binding of mLF-DTA was reduced at shorter incubations and longer incubations taper off this difference. Gel shift assay suggested 8-10% less binding of mLF-DTA as compared to LF-DTA. In conclusion His35 is important for binding and His42 is critical and confers proper conformation for LF binding to PA.

Animals↗
PubMedDate not supplied

A weight-of-evidence approach for assessing interactions in chemical mixtures.

The risk assessment process must encompass all available toxicological data and scientific evidence on the plausible toxicities of a chemical or chemical mixture. As an extension to the approaches used to conduct risk assessments on chemical mixtures, a preliminary scheme, analogous to the IARC classification of carcinogens, is proposed to express the weight of evidence for the interactions in binary mixtures. This scheme is based on composite representation of all the toxicological evidence from animal bioassays and human data, pharmacokinetics studies, metabolism studies, and structure activity relationships. In addition, factors such as the relevance of route, duration and sequence of exposure, toxicological significance of interactions and the quality of in vivo and in vitro data are taken into consideration. The scheme yields an alphanumeric classification that can be used for qualitative risk assessment, and has the potential, as demonstrated in this paper, for quantitative application to site-specific risk assessments. Furthermore, the scheme can be used to estimate interactions or form hypotheses concerning binary interactions. It is flexible and allows all pertinent information to be incorporated in a methodical and consistent manner. Research is needed to identify interaction patterns for simultaneous and sequential exposure scenarios of chemical pollutants in order that this scheme may be developed further and its usefulness and limitations may be tested.

Benzene Derivatives↗
PubMedDate not supplied

Time-dependent effects of lead on rat reproductive functions.

The effects of exposure to lead on endocrine function and the reproductive parameters were studied in pubertal rats treated with 1.0 g l-1 lead acetate in drinking water for 20 days (subacute group) or 9 months (chronic group) in addition to i.v. injections of lead acetate (0.1 mg 100 g-1 body wt.) every 10 (subacute group) or 15 days (chronic group). Although basal levels of testosterone were higher both in plasma and in testes of acutely intoxicated animals, the circulating levels of luteinizing hormone (LH) were not affected in either group, nor was the LH-releasing hormone content of the median eminence. The density of [125I]LH/human chorionic gonadotrophin (hCG) binding sites in testicular homogenates was reduced by saturnism in both groups, concomitant with a significantly increased apparent affinity constant of the hormone-receptor complex. These data can be viewed as the result of a mixture of specific lead toxicity (e.g. at the enzyme level) with other more general actions (e.g. at the level of the hypothalamus-pituitary-testicular axis).

Animals↗
PubMed2003

Effects of riboflavin photoproducts on microbial activity during photosensitization of atrazine transformation.

The contributions and effects of photolysis and microbial assemblages to 37.6 mg/L riboflavin-sensitized atrazine transformation were studied along with the toxicity of the intermediate mixtures. High-performance liquid chromatography analysis revealed that riboflavin significantly enhanced the phototransformation of atrazine (10 mg/L) by reducing the parent compound concentration to less than 20% in 72 h. However, radiotracer measurements indicated atrazine was not mineralized to the same degree after 3 days of exposure. We hypothesize that riboflavin-sensitized transformation of atrazine is primarily photochemical; however, the biological component seems to promote overall atrazine degradation under solar irradiation. Based on the results of spread plate counting or 14C-glucose mineralization measurement, at a test concentration of 12.1 mg/L, lumichrome (a major riboflavin photoproduct) was found to be nontoxic to the test microbial assemblages in a reservoir water sample. Other riboflavin photoproducts and/or certain chemically reactive species were speculated to cause a cytotoxic effect. Overall, our data indicate that riboflavin may be an economical photosensitizing agent for atrazine degradation, but the apparent photoinduced cytotoxicity observed during transformation is of concern to the microbial assemblages that are needed for complete remediation. Further investigation into why the biotic component enhances riboflavin phototransformation of atrazine and the time frame of microbial recovery from riboflavin inhibition is needed. Such work may lead to cost-effective surface water treatment systems involving combined photochemical and microbial degradation processes.

Atrazine↗
PubMed1994

Contaminants in fishes from Great Lakes-influenced sections and above dams of three Michigan rivers. II: Implications for health of mink.

Populations of mink (Mustela vison) have declined in many areas of the world. Such declines have been linked to exposures to synthetic, halogenated hydrocarbons. In the Great Lakes region, mink are fewer in areas along the shore of the Great Lakes and their tributaries where mink have access to fish from the Great Lakes. Recently, there has been discussion of the relative merits of passage of fishes around hydroelectric dams on rivers in Michigan. A hazard assessment was conducted to determine the potential for adverse effects on mink, which could consume such fishes from above or below dams on the rivers. Concentrations of organochlorine insecticides, polychlorinated biphenyls (PCBs), 2,3,7,8-tetrachlordibenzo-p-dioxin equivalents (TCDD-EQ), and total mercury were measured in composite samples of fishes from above or below hydroelectric dams on the Manistee and Muskegon Rivers, which flow into Lake Michigan, and the Au Sable River, which flows into Lake Huron. Concentrations of organochlorine insecticides, PCBs, and TCDD-EQ were all greater in fishes from below the dams than those from above. Concentrations of neither organochlorine insecticides nor mercury in fishes are currently a risk to mink above or below the dams. All of the species of fishes collected from downstream of the dams contained concentrations of PCBs and TCDD-EQ, which represent a hazard to mink. The hazard index for PCBs was less than one for the average of all species from the upstream reaches of the Manistee and Au Sable Rivers, but not the Muskegon. The hazard index (concentration in fish/NOAEC) was greater than 1 for all of the species collected from below the dams, in all three rivers. The greatest hazard index was observed for carp (Cyprinus carpio) downstream on the Muskegon River. Because the concentrations of PCBs used in the hazard assessment were corrected for relative toxic potencies, the hazard ratios based on PCBs should be similar to those based on TCDD-EQ. This was found to be true. Thus, either total PCBs or TCDD-EQ could be used as the critical toxicant in the hazard assessment. However, if uncorrected concentrations of PCBs, expressed as Aroclors, were used in the hazard assessment, the toxicity of the weathered mixture would have been underestimated by approximately five-fold, and, in that instance, TCDD-EQ would be the critical contaminant for the hazard assessment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Feed↗
PubMed1977

Acute toxicities of selected herbicides to fingerling channel catfish, Ictalurus punctatus.

A scan of the acute toxicities of eighteen common herbicides to one-year-old channel catfish (Ictalurus punctatus) was conducted. Herbicides causing less than 10% mortality in 48 hr at 10 ppm were: alanap, chloramben, 2,4-D acid, 2,4-D dimethyl amine salt, dalapon, diuron, DSMA, EPTC, fluometuron, metribuzin, monuron, MSMA, nitralin and 2,4,5,-T. The 96-hr LC50 values in pp6 for four nerbicides found toxic were: propanil, 3796; trifluralin, 417; bensulide, 379; and DNBP 118. The toxicity of Dyanap, a mixture of DNBP and alanap, was lower than that of DNBP; there was no apparent synergism between DNBP and alanap in the mixture.

Animals↗
PubMed1976

[The effect of coffee and coffee components on the stomach muscle].

The isolated stomach muscle strip preparation works well when given pure compounds which are stable and non-toxic. When complex test mixtures such as coffee are used, however, the results are more difficult to interpret. This is probably due to non-specific effects of such mixtures, e.g. induction of changes in organ bath pH, etc. In spite of the above remark, differences in the effects of decaffeinated and normal instant coffees were clearly seen. The so-called "wholesome" coffees gave results identical to those obtained with normal instant coffee. In general, coffee induced muscle contraction followed by relaxation. Choline (possibly together with potassium) would appear to be responsible for the contractions observed, and caffeine for the relaxation.

Animals↗
PubMed1991

Piperonyl butoxide as a tool in aquatic toxicological research with organophosphate insecticides.

Experiments were conducted to determine the effects of piperonyl butoxide, a synthetic methylenedioxyphenyl inhibitor of cytochrome(s) P450, on the toxicity of organophosphate insecticides to three cladoceran test species: Ceriodaphnia dubia. Daphnia magna, and Daphnia pulex. Coadministration of piperonyl butoxide effectively reduced the acute toxicity of four metabolically activated organophosphates (parathion, methyl parathion, diazinon, and malathion) and did not affect the toxicity of three organophosphates not requiring metabolic activation (dichlorvos, chlorfenvinphos, and mevinphos). These results indicate that piperonyl butoxide may be an effective tool in toxicological research focused upon identifying specific compounds responsible for toxicity in complex aqueous mixtures.

Animals↗
PubMed1992

Integrated assessment of contaminated sediments in the lower Fox River and Green Bay, Wisconsin.

Samples of sediment and biota were collected from sites in the lower Fox River and southern Green Bay to determine existing or potential impacts of sediment-associated contaminants on different ecosystem components of this Great Lakes area of concern. Evaluation of benthos revealed a relatively depauperate community, particularly at the lower Fox River sites. Sediment pore water and bulk sediments from several lower Fox River sites were toxic to a number of test species including Pimephales promelas, Ceriodaphnia dubia, Hexagenia limbata, Selenastrum capricornutum, and Photobacterium phosphorum. An important component of the observed toxicity appeared to be due to ammonia. Evaluation of three bullhead (Ictalurus) species from the lower Fox River revealed an absence of preneoplastic or neoplastic liver lesions, and the Salmonella typhimurium bioassay indicated relatively little mutagenicity in sediment extracts. Apparent adverse reproductive effects were noted in two species of birds nesting along the lower Fox River and on a confined disposal facility for sediments near the mouth of the river, and there were measurable concentrations of potentially toxic 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), and planar polychlorinated biphenyls (PCBs) both in the birds and in sediments from several of the study sites. Based on toxic equivalency factors and the results of an in vitro bioassay with H4IIE rat hepatoma cells, it appeared that the majority of potential toxicity of the PCB/PCDF/PCDD mixture in biota from the lower Fox River/Green Bay system was due to the planar PCBs. The results of these studies are discussed in terms of an integrated assessment focused on providing data for remedial action planning.

Animals↗
PubMed1991

Efficacy of an oximate-based skin decontaminant against organophosphate nerve agents determined in vivo and in vitro.

Recent Canadian research efforts have been directed towards the development of a reactive skin decontaminant (RSD) lotion active against classical nerve agents and mustard. The formulation presently under study consists of a 1.25 molal solution of potassium 2,3-butanedione monoximate (KBDO) in polyethylene glycol methylether 550. Although this formulation has shown good efficacy, concern has been expressed as to the potential toxicity of the reaction products of KBDO and organophosphate (OP) nerve agents. This report details the high efficacy of this lotion in inactivating OPs as measured by the systemic toxicity of the OP/RSD mixtures in rats. In addition, primary cultures of chick embryo neurons were also used to test the efficacy of the RSD. By relating the anticholinesterase activity in these cultures of the OP/RSD mixture to that of pure OP standards, a sensitive measure of the value of the RSD in inactivating tabun, sarin, soman and VX was obtained. Experiments with all four nerve agents in this in vitro system provided a good correlation with the in vivo data, and also indicated that the inactivation process was time- and agent-dependent and also related to the ratio of OP to RSD.

Acetylcholinesterase↗