Lethal effects assessment

Much of this research could, in concept, be extended to sub-lethal effects. There is already some indication of a relationship between the smoke concentrations that cause death and those that result in physical collapse of the test animals (16). However, more subtle effects, such as decrease in human mental acuity, are expected to be very difficult to assess using rodent data. 

To provide a better understanding of toxic impacts on aquatic ecosystems, cause-effect relationships between changes in biodiversity and the impact of environmental pollution as causative factor as well as the underlying processes. This included the assessment of sub-lethal effects in vitro and in vivo as early warning strategies and of their strength to predict potential hazards to the ecosystem. 

Testing on animals may provide initial information on the effect of a possible shortterm exposure on human health. Acute toxicity is defined as the toxic effect of a substance after a single oral, dermal, or inhalative application. For acute oral toxicity, for instance, LD50 is defined as the amount of substance expressed in mg per kg body weight which has a lethal effect on 50% of the test animals after a single oral application. Such tests are useful in that they assess the toxicity of a material relative to that of other known compounds. 

There are very few in vivo genotoxicity studies. Only two in vivo studies were located, and both assessed the dominant lethal effects. The results were negative for both studies, implying that neither heptachlor nor heptachlor epoxide are genotoxic to the germ-line cells of male mice when tested alone or as a mixture (Arnold et al. 1977 Epstein et al. 1972). Refer to Table 2- 3 for a summary of these results of in vivo studies. 

Dominant lethal assays in mice were performed using o- and p-cresols. Male mice were given a single dose of o-cresol (0, 75, 250, or 750 mg/kg) or p- cresol (0, 100, 275, or 550 mg/kg) by gavage in corn oil and mated to untreated females in order to assess dominant lethal effects. The matings were continued for 6 weeks so that all stages of male germ cell development were tested. 

Ashby, J. Clapp, M.J.L. (1995) The rodent dominant lethal assay a proposed format for data presentation that alerts to psendo-dominant lethal effects. Mutat. Res., 330, 209-218 Ashby, J., Brady, A., Elcombe, C.R., Elliott, B.M., Ishmael, J., Odnm, J., Tngwood, J.D., Kettle, S. Purchase, IF. (1994) Mechanistically-based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis. Hum. exp. Toxicol., 13 (Suppl. 2), S1-S117... 

During exposure to contaminated sediments, test organisms can concentrate chemicals in their tissue and exhibit measurable (sub)lethal effects linked to accumulated substances. In the field of sediment toxicity assessment, it is noteworthy to mention that some studies have been conducted to characterize both exposure and biological effects in parallel. Exposure to contaminants can be gauged by measuring their concentrations in water/sediment and tissue, and effects can be estimated with endpoints such as survival and growth. These studies are important, for example, to detect threshold concentrations at which chemicals begin to exert adverse effects. As such, they can be useful to recommend effective chemical quality standards that will be protective of aquatic life. 

Animal disease models for acquired AT deficiency, such as Escherichia cofi-induced sepsis, were used to assess the biological consistency of the rhAT compared to hpAT. Although in these models the exact contributions of the anti-coagulant and anti-inflammatory properties of AT are still somewhat controversial [81], they do allow for some comparison of the properties of rhAT with hpAT. Human plasma-derived AT has been shown to prevent the lethal effects of experimentally induced sepsis in several animal models [82-89], and to block cytokine production in vitro. To date, several dose- response studies have been performed with rhAT in rats (GTC Biother-... 

Measurements of behavioral endpoints in honey bees should provide an effective assessment of hazards caused by crop protection chemicals especially when applied to melliferous plants. Under laboratory conditions, the conditioned proboscis extension (CPE) assay provides detectable sub-lethal effects due to pesticides, and also to gene products potentially used in plant genetic engineering (see other chapters of this book). Impairment in olfactory learning abilities have been shown for chemical concentrations at which no additional mortality occurred. Thus, the use of the CPE assay as a method to evaluate the potential effect on the honey bees foraging behavior can help to assess the toxicity of chemicals in a more comprehensive way than by considering the mortality endpoint alone. The CPE procedure can be used to compare responses to different chemicals (Table... 

Released toxic gas can have injuring or lethal effects with stochastic character for people (3rd task category). In toxic gases transportation risk assessment we consider only lethal effects, due to very difficult categorization of injury effects and with it related impracticabdity of several transport routes risk comparison. 

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