Acute toxicity analysis

In many cases, there is difficulty in preserving residues in samples after collection and prior to pesticide analysis which coincides with a rapid further degradation and mineralization of the pesticide residues under most environmental conditions. Storage stability studies and studies on the reactivity of sample collection equipment in addition to field quality assurance procedures can help address some of these questions. Concerns are accentuated for compounds that have short half-lives in the environment but still have high acute toxicity. 

Toxicological properties Acute toxicity (by two routes of admission) Skin irritation Eye irritation Skin sensitization 28 days subacute toxicity Ames test In vitro metaphase analysis (or mouse micronucleus test)... 

The association between low TPMT activity and excessive hematological toxicity has been recognized [31, 35, 37]. Molecular analysis of the TPMT genotype is able to identify patients at risk for acute toxicity from thiopurines. A recent study involving 180 children identified that the TPMT genotype plays an important role in a patients tolerance to 6-MP therapy [51]. Two of the patients, who were TPMT-de-... 

Tousignan JD, Gates AL, Ingram LA et al (2002) Comprehensive analysis of the acute toxicities induced by systemic administration of cationic lipid Plasmid DNA complexes in mice. Hum Gene Ther 11 2493-2513... 

Toxicity in estuarine sediments—use of Mutatox and Microtox to evalu- 173 ate the acute toxicity and genotoxicity of organic sediments Toxicity tests for the analysis of pore water sediment a comparison of 4 174... 

Williamson, E.G., S.F. Long, M.J. Kallman, and M.C. Wilson. 1989. A comparative analysis of the acute toxicity of technical-grade pyrethroid insecticides and their commercial formulations. Ecotoxicol. Environ. Safely 18 27-34. 

The New Jersey Department of Environmental Protection uses the TXDS method of consequence analysis to estimate potentially catastrophic quantities of toxic substances, as required by the New Jersey Toxic Catastrophe Prevention Act (TCPA). An acute toxic concentration (ATC) is defined as the concentration of a gas or vapor of a toxic substance that will result in acute health effects in the affected population and 1 fatality out of 20 or less (5% or more) during a 1-hr exposure. ATC values, as proposed by the New Jersey Department of Environmental Protection, are estimated for 103 extraordinarily hazardous substances and are based on the lowest value of one of the following (1) the lowest reported lethal concentration (LCLO) value for animal test data, (2) the median lethal concentration (LC50) value from animal test data multiplied by 0.1, or (3) the IDLH value. 

Olson, H., Fabian, R., Greener, Y., Pack, F., Zelinger, D. and Dean, J. (1990). Reduction in animals used for acute toxicity testing based on retrospective analysis. Toxicologist 141 (abstract). 

When using purified triolein, most samples are amenable to bioassay after di-alytic enrichment. For example, Microtox bioassay of dialysates of SPMDs shows that the SPMDs made with the purified triolein have lower acute toxicities than dialysates from SPMDs made from unpurified triolein (Johnson, 2001). Finally, examination of the dialysates using the yeast estrogen screen (YES) assay (Routledge and Sumpter, 1996) demonstrated that the purification procedure removes all background estrogenic activity (Lebo et ah, 2004). Use of triolein purified by this process expands the potential applicability of SPMD sample extracts to include numerous bioassay procedures (see Chapter 6) and GC-MS as a standard analysis technique. 

Banerjee, T.K. and Paul, V.I. Estimation of acute toxicity of ammonium sulphate to the fresh water catfish, Heteropneustes fosslLls. II. A histopathological analysis of the epidermis, Biomed. Environ. Sci, 6(l) 45-58, 1993. 

The acute toxicity and oxidative effects of nano-scale Ti02 depend on the size of the nanoparticle (bulk Ti02 is positively nontoxic) and increase notably through illumination, as this leads to the formation of hydroxyl radicals [74], further indicating oxidative stress as a major candidate for the mechanism of action of NP toxicity. However, a recent microarray analysis of the transcriptome of zebrafish embryos treated with Ti02 NP showed no major increase of transcripts related to oxidative stress. Instead, significant effects were observed on expression of genes involved in circadian rhythm, kinase activity, vesicular transport, and immune response [75]. 

A Dutch smdy (Wilschut et al. 1998, as reviewed in Vermeire et al. 1999) has evaluated route-to-route extrapolation on the basis of absorption or acute toxicity data. Data were collected primarily on dermal and inhalation repeated dose toxicity. An extrapolation factor, defined as the factor that is applied in route-to-route extrapolation to account for differences in the expression of systemic toxicity between exposure routes, was determined for each substance by using data on absorption and acute toxicity data. As experimental data on absorption often were not available, default values for absorption were also used to determine an extrapolation factor. Despite a rather large overall database, relatively few data could be used for the evaluation and the selection criteria were modified in order to include data that initially were considered less suitable for data analysis interspecies extrapolation based on caloric demands was introduced, and a factor of 3 was applied in case a LOAEL instead of a NOAEL was available. The choice of NOAELs for different exposure routes known for a substance suitable for analysis was based primarily on the same effect, but this criterion could not be maintained. 

Veith, G.D., Mekenyan, O.G., Ankley G.T. and Call, D.J. (1995) A QSAR analysis of substituent effects on the photoinduced acute toxicity of PAHs. Chemosphere, 30, 2129-2142. 

Comprehensive toxicity studies are carried out by animal testing in order to ascertain whether the product exhibits any short-term or long-term toxicity. Acute toxicity is usually assessed by administration of a single high dose of the test drug to rodents. Both rats and mice (male and female) are usually employed. The test material is administered by two means, one of which should represent the proposed therapeutic method of administration. The animals are then monitored for 7-14 days, with all fatalities undergoing extensive post-mortem analysis. 

Schiiurmann, G., QSAR Analysis of the Acute Toxicity of Oxyethylated Surfactants. Chemosphere, 1990 21, 467-478. 

Marchini, S., L. Passerini, D. Cesareo, and M.L. Tosato (1988). Herbicidal triazines Acute toxicity on daphnia, fish, and plants and analysis of its relationships with structural factors. Ecotoxicol. Environ. Safety 16 148-157. 

Dutka, B. (1989b) Daphnia magna 48 hours static bioassay method for acute toxicity in environmental samples, in B. Dutka (ed.), Methods for Toxicological Analysis of Waters, Wastewaters and Sediments, National Water Research Institute, Environment Canada, Burlington, Ontario, pp. 55-59. 

In the MPD-SAR study, the USEPA and the European Union compared the predicted and measured ECs for the European Union s new chemicals. The measured ECs were those reported in the European Union s MPD set of experimental toxicity summaries. When the USEPA-predicted ECs for fish and daphnid acute toxicity values were compared to the appropriate MPD-measured acute values, there was, respectively, 77% and 59% agreement, 7% and 19% underprediction, and 16% to 23% overprediction by the USEPA. Potential reasons for the under- and overprediction were investigated, and 17 of the underpredictions and 21 of the overpredictions remained unresolved. Therefore, studies that had potential problems were eliminated, and the analysis was repeated. The highest quality subset of the data indicated 87% and 79% agreement between predictions and measured values. 

Lee G, Ellersieck MR, Mayer FL, Krause GF. 1995. Predicting chronic lethality of chemicals to fishes from acute toxicity test data multifactor probit analysis. Environ Toxicol Chem 14 345-349. 

Schuurmann, G., QSAR analysis of the acute toxicity of organic phosphorothionates using theoretically derived molecular descriptors, Environ. Toxicol. Chem., 9, 417-428, 1990. 

Karabunarliev, S., Mekenyan, O.G., Karcher, W., Russom, C.L., and Bradbury, S.P., Quantum-chemical descriptors for estimating the acute toxicity of electrophiles to the fathead minnow (Pimephales promelas) an analysis based on molecular mechanisms, Quant. Struct.-Act. Relat., 15, 302-310, 1996a. 

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