Toxic response

Health and Safety Factors. Boron trifluoride is primarily a pulmonary irritant. The toxicity of the gas to humans has not been reported (58), but laboratory tests on animals gave results ranging from an increased pneumonitis to death. The TLV is 1 ppm (59,60). Inhalation toxicity studies in rats have shown that exposure to BF at 17 mg/m resulted in renal toxicity, whereas exposure at 6 mg/m did not result in a toxic response (61). Prolonged inhalation produced dental fluorosis (62). High concentrations bum the skin similarly to acids such as HBF and, if the skin is subject to prolonged exposure, the treatment should be the same as for fluoride exposure and hypocalcemia. No chronic effects have been observed in workers exposed to small quantities of the gas at frequent intervals over a period of years. 

The mode of action has not yet been elucidated but the manufacturer states that it probably behaves like the herbicide triflurolin and its congeners. These materials inhibit cell division by binding to tubuHn thereby internipting micro-tubule development. This, in turn, stops spindle fiber formation essential to mitosis and cell division. Experiments with C-labeled Prime+ show that it is acutely toxic to fish with estimated LC q (96 h) of less than 100 ppb for rainbow trout and bluegiU. sunfish. However, channel catfish did not exhibit any toxic response at the maximum attainable water concentration (10). 

Materials that produce harmful effects must come into close stmctural or functional relationship with the tissue or organ they may affect. As a result, they can physically or chemically interact with particular biological components in order to effect the toxic response. 

If possible, there should be measurement of the toxic effect in order quantitatively to relate the observations made to the degree of exposure (exposure dose). Ideally, there is a need to determine quantitatively the toxic response to several differing exposure doses, in order to determine the relationship, if any, between exposure dose and the nature and magnitude of any effect. Such dose—response relationship studies are of considerable value in determining whether an effect is causally related to the exposure material, in assessing the possible practical (in-use) relevance of the exposure conditions, and to allow the most reasonable estimates of hazard. 

The biological response to chemical insult may take numerous forms, depending on the physicochemical properties of the material and the conditions of exposure. Listed below are some of the more significant and frequendy encountered types of injury or toxic response they may be defined in terms of tissue pathology, altered or aberrant biochemical processes, or extreme physiological responses. 

Time of Dosing. The time of day, or day of the year, may influence the toxic response. These changes reflect diurnal and seasonal variations in biochemical and physiological profiles, which may influence toxicity through a variety of mechanisms. 

Formulation. The formulation of a material may have a significant influence on its potential to cause toxic injury. Eor example, solvents may facihtate or retard the penetration and absorption of a chemical, resulting in enhancement or suppression of a toxic response, respectively. 

Impurities. The presence of impurities may modify the toxic response, particularly if they have high toxicity. 

Animal and Human Toxicity. The acute toxicity of lindane depends on the age, sex, and animal species, and on the route of adrninistration. The oral LD q in mice, rats, and guinea pigs is 86, 125—230, and 100—127 mg/kg, respectively. In contrast, most of the other isomers were considerably more toxic (94,95). Some of the other toxic responses caused by lindane in laboratory animals include hepato- and nephotoxicity, reproductive and embryotoxicity, mutagenicity in some short-term in vitro bioassays, and carcinogenicity (80). The mechanism of the lindane-induced response is not known. Only minimal data are available on the mammalian toxicides of hexachlorocyclopentadiene. 

Capen, C. C. (1996). Toxic responses of the endocrine system. Jn Casarett and DouU s Toxicology The Baste Science, of Poisons (C. D. Klaassen, Ed. , pp. 617-640. McGraw-Hill, New York. 

Since the fundamental mcclumisms tliat cause toxic responses are not fully understood, toxicological findings are largely based on observations. Altliough some of the toxicological information relating to hmnans is based on human experience, tlie majority of this information is derived from animal experimentation. 

For a variety of reasons it is difficult to precisely evaluate toxic responses caused by exposures (particularly acute ones) to hazardous chemicals. Five of these toxic responses are briefly discussed below. 

For the overwhelming majority of substances encountered in industry, there are not enough data on toxic responses of humans to permit an accurate or precise assessment of the substance s hazard potential. Frequently, the only data available are from controlled experiments conducted with laboratory animals. In such cases, it is necessary to extrapolate from effects observed in animals to effects likely to occur in... 

Risk characterization is tlie process of estimating tlie incidence of a healtli effect under tlie various conditions of human or animal exposure as described in the exposure assessment. It evolves from both dose exposure assessment and toxicity response assessment. The data are then combined to obtain qualitative and quantitative expression of risk. 

Materials produced by crystalliferous bacilli which elicit a toxic response in susceptible insects may be separated into two types. The first type, the true toxins, include the crystalline protein inclusion body the parasporal body of Hannay (14)], a heat-stable, water-soluble exotoxin active against flies, a heat-stable, dialyzable water-soluble exotoxin, toxic to Lepidoptera on injection (23), and a heat-labile, water-soluble, filterable exotoxin, toxic toward larch sawfly larvae (Hymenoptera) which was reported by Smirnoff (31). 

Water-Soluble Exotoxins. In this area, we enter into the slightly muddy waters of the lower molecular weight compounds which elicit toxic responses in susceptible host insects. Without reference to molecular identity, it is possible to sift through the various reports on the effects of bacillus-produced soluble exotoxins and recognize three possible types of material which are produced under appropriate conditions by specific strains of bacilli ... 

Toxicology ( toxicogenomics), to identify potential human and environmental toxicants, and to find correlations between toxic responses to toxicants and changes in the genetic profiles of the objects exposed to such toxicants... 

Persistent activation of PPARa can induce the development of hepatocellular carcinoma in susceptible rodent species by a nongenotoxic mechanism, i.e., one that does not involve direct DNA damage by peroxisome proliferator chemicals or their metabolites. This hepatocarcinogenic response is abolished in mice deficient in PPARa, underscoring the central role of PPARa, as opposed to that of two other mammalian PPAR forms (PPARy and PPAR5), in peroxisome proliferator chemical-induced hepatocarcinogenesis. Other toxic responses, such as kidney and testicular toxicities caused by exposure to certain phthalate... 

Bock KW, Kohle C (2006) Ah receptor dioxin-mediated toxic responses as hints to deregulated physiologic functions. Biochem Pharmacol 72 393-404... 

Anthony DC, Montine TJ, Graham DG. 1996. Toxic responses of the nervous system. In Wonsiewicz MJ, Sheinis EA, ed. Casarett and Doull s toxicology The basic science of poisons. New York, NY McGraw-Hill, 475-476. 

Huling SG, Pope DF, Matthews JE, et al. 1995. Wood preserving waste-contaminated soil Treatment and toxicity response. In Hinchee RE et al., ed. Bioremediation of recalcitrant organics. Columbus, OH Battell Press, 101-109. 

It should elicit biochemical and toxic responses that are characteristic of 2,3,7,8,-TCDD. 

TOXIC RESPONSES THAT SHARE COMMON PATHWAYS OF EXPRESSION... 

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