Criteria of Toxicity

Clearly there are many different kinds of toxic effect as will be discussed in chapter 6 and also many different ways of detecting and measuring them. However, it is necessary at this stage to consider in general terms what is meant by the term toxic response or toxic effect. This 

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it is important to distinguish between toxic effects occurring at the point or site of exposure (e.g., the stomach), so-called local effects, and those toxic effects occurring at a site distant from the site of exposure, known as systemic effects. Local effects are usually limited to irritancy and corrosive damage such as from strong acids, which occur immediately but can be reversible. The one exception is sensitization, which involves the immune system but is often manifested at the site of the exposure (e.g., skin) although may be delayed. 

It is also important at this point to identify that some effects may be reversible, whereas others are irreversible and that this can be for a number of reasons. Reversibility may be due to replacement of an inhibited enzyme, for example, or repair of damaged tissue. Irreversibility could be due to inability to repair a damaged organ or tissue. If this organ has a crucial function, then the organism may die. 

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Finally, unit mg/m is also used to express LEV and AEV. Furthermore, g/m3 or mg/l units are used in regulations to specify the criteria of toxicity by inhalation of substance. The equation below expresses Cgq in g/m or mg/i ... 

In in vitro systems, criteria of toxicity will generally be measurements of either specific biochemical changes, such as ATP level or protein synthesis, or general indicators such as cell metabolic activity, viability, or membrane damage as indicated by dye uptake or enzyme leakage. 

Examination of these assumptions indicates that there are various factors that may affect the relationship. Furthermore, it is also assumed that there is a method for measuring and quantifying the toxic effect in question. As already indicated, there are many possible endpoints or criteria of toxicity, but not all are appropriate. 

The literature review included compounds, investigators, animal species, and criteria of toxicity which varied greatly. Despite the welter of information, an agreement with the data of... 

All pesticide products meeting the criteria of toxicity category II shall bear on the front panel the signal word WARNING. 

Human Hazard Signal Word (162.10(hXl)(i))—The signal word DANGER has been designated by EPA as the word which must appear on the labels of all pesticide products which meet the criteria of Toxicity Category I. Furthermore, if a product meets those criteria due to its oral, dermal, or inhalation... 

In order to check suitability and sensitivity of the bioassay method, an experiment was carried out with groups of two-day-old ducklings that were fed known levels of aflatoxin for four weeks. Results of mortality and growth rate as criteria of toxicity were treated statistically. Ducklings livers were also examined for... 

In the NCMS investigation [4], Sn-5Sb was included in the initial list. However, based on the down-selection criteria of toxicity and alloy properties assessment, it was not selected for a manufacturability assessment. It is stated in the report that Sb is highly toxic when inhaled or ingested and has the same Lethal Dose, Lower Limit (LDLo) as Cd. Therefore it was recommended to not consider Sb as a possible major constituent in Pb-free solders, although Sb has been present in solders utilized for military applications since the 1940s but only in small amounts, typically less than 0.5% [4j. 

Significant piopeities of insulation (Table 1) include tliermal conductivity, fite resistance, and ntiniinal production of toxic gases primarily during combustion. Other criteria include water-vapor permeability, resistance to water absorption, and dimensional stability over prolonged periods of submission to extreme environments. 

Air Quality Criteria forTead Supplement to the 1986 Addendum, U.S. EPA, Environmental Criteria and Assessment Office, Washington, D.C., 1990. Technical Support Document to Proposed Airborne Toxic Control Measure for Emissions of Toxic Metalsfrom Non-Ferrous Metal Melting, State of California Air Resources Board, Stationary Source Division, Sacramento, Calif., 1992. 

Biphenyl is defined as a toxic chemical under, and subject to, reporting requirements of Section 313 of Tide 111 of the Superfund Amendments and Reauthori2ation Act (SARA) of 1986 and 40 CFR, Part 372 under the name biphenyl. It is identified as a ha2ardous chemical under criteria of the OSHA Ha2ard Communication Standard (29 CFR 1910.1200). 

Although biphenyl and the terphenyls fall under the ha2ardous chemical criteria of the OSHA Ha2ard Communications Standard, the products themselves are fairly low in toxicity and do not constitute a serious industrial ha2ard. Some relevant exposure and toxicity data are summari2ed in Tables 5 and 6. 

States have made substantial recent progress in the adoption, and EPA approval, of toxic pollutant water-quahty standards. Furthermore, virtually all states have at least proposed new toxics criteria for priority toxic pollutants since Section 303 (c) (2) (B) was added to the CWA in February of 1987. Unfortunately, not all such state proposals address, in a comprehensive manner, the requirements or Section 303 (c) (2) (B). For example, some states have proposed to adopt criteria to protect aquatic hfe, but not human health other states have proposed human health criteria that do not address major exposure pathways (such as the combination of both fish consumption and drinking water). In addition, in some cases final adoption or proposed state toxics criteria that would be approved by EPA has been substantially delayed due to controversial and difficult issues associated with the toxic pollutant criteria adoption process. 

From the perspective of ecological integrity called for in the Clean Water Act, any adjustment to the implementation of toxic metals criteria needs to be integrated with both sediment criteria and biological criteria to provide ecosystem protection envisioned by the Act. 

The final article, by S. G. Bell and G. A. Codd of the University of Dundee Department of Biological Services, is concerned with detection, analysis, and risk assessment of cyanobacterial toxins. These can be responsible for animal, fish, and bird deaths and for ill-health in humans. The occurrence of toxic cyanobacterial blooms and scums on nutrient-rich waters is a world-wide phenomenon and cases are cited from Australia, the USA, and China, as well as throughout Europe. The causes, indentification and assessment of risk, and establishment of criteria for controlling risk are discussed. 

TCDF is not very toxic to the mouse (acute oral LDjq < 6000 pg/kg) but is highly toxic to the guinea pig (acute oral LD50 5-10 pg/kg). Symptoms of toxicity in the gninea pig were similar to those fonnd with 2,3,7,8-TCDD. Thus, the selectivity pattern was similar to that for 2,3,7,8-TCDD, but toxicity was considerably less (see Environmental Health Criteria 88). 

Mechanistic studies have shown that TBT and certain other forms of trialkyltin have two distinct modes of toxic action in vertebrates. On the one hand they act as inhibitors of oxidative phosphorylation in mitochondria (Aldridge and Street 1964). Inhibition is associated with repression of ATP synthesis, disturbance of ion transport across the mitochondrial membrane, and swelling of the membrane. Oxidative phosphorylation is a vital process in animals and plants, and so trialkyltin compounds act as wide-ranging biocides. Another mode of action involves the inhibition of forms of cytochrome P450, which was referred to earlier in connection with metabolism. This has been demonstrated in mammals, aquatic invertebrates and fish (Morcillo et al. 2004, Oberdorster 2002). TBTO has been shown to inhibit P450 activity in cells from various tissues of mammals, including liver, kidney, and small intestine mucosa, both in vivo and in vitro (Rosenberg and Drummond 1983, Environmental Health Criteria 116). 

Technology is called green if it uses raw materials efficiently, such that the use of toxic and hazardous reagents and solvents can be avoided while formation of waste or undesirable byproducts is minimized. Catalytic routes often satisfy these criteria. 

The criteria for choosing inhibitors in this study were the ability to compete with diethanolamine for the nitrite and lack of toxicity. An attempt was made to cover as broad a group as possible within the limits of feasibility. Ascorbic acid in its water soluble form and its oil soluble form, the palmitate, represent the enediols, Sorbate is a diene fatty acid which has been shown to inhibit nitrosation (10), Since the pK of sorbic acid is 4,76, at the pH of these experiments, both water soluble sorbate ion and oil soluble sorbic acid are present in significant amounts. Sodium bisulfite is a strong inorganic reducing agent which has an acceptable lack of toxicity at the concentration... 

The only difficulty in this method (in addition to the calculations, which are easily carried out using computers) is the fact that it is impossible to analyse tables with values that are missing, so there is a need to choose substances for which there are a whole range of LC and LD values. Since this is impossible, three tables were used, which all have in common the L050 variables for rat and mouse, orally and by intraperitoneal means of penetration, so that the coherence of the three tables and a strong enough relationship between them could be ablished. The purpose was to determine, if, in the absence of one of the classification criteria set by regulation, it was possible to choose another available criterion to determine the risk level of toxicity. 

Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982 5(6) 649-655. 

The Food Quality Protection Act (FQPA) of 1996 mandated that the US EPA carry out risk assessments that consider the cumulative effects of exposure to pesticides having a common mechanism of toxicity, as well as consider exposure to each pesticide by various routes of exposure (e.g., dermal, dietary, inhalation) and sources (e.g., residues in food and water) in an aggregate manner [19]. To accomplish this, there needs to be sufficient evidence supporting a common adverse effect that is associated with a common mechanism of action in specific target tissues. To date, the required criteria necessary to establish a common mechanism of toxicity with a specific toxic effect for the pyrethroids are not available [1,8,98]. 

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