Toxic Effects of Chemical Compounds

In risk characterization, step four, the human exposure situation is compared to the toxicity data from animal studies, and often a safety -margin approach is utilized. The safety margin is based on a knowledge of uncertainties and individual variation in sensitivity of animals and humans to the effects of chemical compounds. Usually one assumes that humans are more sensitive than experimental animals to the effects of chemicals. For this reason, a safety margin is often used. This margin contains two factors, differences in biotransformation within a species (human), usually 10, and differences in the sensitivity between species (e.g., rat vs. human), usually also 10. The safety factor which takes into consideration interindividual differences within the human population predominately indicates differences in biotransformation, but sensitivity to effects of chemicals is also taken into consideration (e.g., safety faaor of 4 for biotransformation and 2.5 for sensitivity 4 x 2.5 = 10). For example, if the lowest dose that does not cause any toxicity to rodents, rats, or mice, i.e., the no-ob-servable-adverse-effect level (NOAEL) is 100 mg/kg, this dose is divided by the safety factor of 100. The safe dose level for humans would be then 1 mg/kg. Occasionally, a NOAEL is not found, and one has to use the lowest-observable-adverse-effect level (LOAEL) in safety assessment. In this situation, often an additional un-... 

A code of two letters followed by seven digits is a reference to Registry of Toxic Effects of Chemical Substances (RTECS) of National Institute for Occupational Safety and Health/Occupational Safety and Health Administration (NIOSH/OSHA). Standard samples are commercially available for most compounds with reference to protocols of die US Environmental Protection Agency (EPA) and the US Pharmacopea (USP)74. 

Registry of Toxic Effects of Chemical Substances (RTECS) number Many compounds are... 

A large compilation of information on the toxic effects of chemical snbstances is NIOSH s RTECS, which included in March 2004 abont 158000 snbstances and many of the compounds listed in Table 11 2,735 jjgjg table). The regnlatory char-... 

For the purposes of estimating the potential toxicity of the chemical mixture, it is assumed the toxicity of the individual component compounds is additive. Data from the Registry of Toxic Effects of Chemical Substances (RTECS) and from the Hazardous Substances Data Bank will be accepted, as well as peer-reviewed primary data. 

Functional interactions are those in which both of the two chemicals affect a bodily system perhaps by different mechanisms, and either increase or decrease the combined effect. For example, both atropine and pralidoxime decrease the toxic effects of organophosphate compounds by different means, a combination of the two antidotes leads to a large increase in effectiveness synergism). 

For most of these compounds more toxicity information is included in the Registry of Toxic Effects of Chemical Substances (RTECS) data base.8 also for a large number of compounds in other tables. Further acid derivatives have been described.107 h Unless otherwise stated. ipr. Oral. 

CDDs and the structurally related CDFs and dioxin-like PCBs are of concern to ATSDR because of the potential of these chemicals to harm health at relatively low doses. As discussed in Section 2.5, many of the toxic effects of these compounds appear to be mediated by a common mechanism, and CDDs frequently occur with CDFs in the environment. Therefore, due to the common mechanism of toxicity, total toxicity of a CDD/CDF mixture probably results from the added contribution (not necessarily linear) of both classes of chemicals. Because of this, the complex issue of appropriate methodology for quantitatively assessing health risks of CDDs and CDFs is currently being evaluated by ATSDR. Additional information on toxic interactions between CDDs and CDFs, as well as PCBs, would facilitate health risk assessment of this class of chemicals. 

Exposure to inorganic chemicals in the workplace has been traditionally evaluated using elemental analysis. However, in recent years some attention has been given to the toxic effects of specific compounds rather than elements, e.g., chromic acid ( ), nickel subsulfide Q), zinc oxide (4.), and sodium hydroxide (5.). It is therefore important that the occupational health chemist develop the capability to identify and quantitate chemical compounds. To this end, X-ray powder diffraction (XRD) is a unique tool for... 

Two types of publications are presented herein. The first set outlines the toxic effects of aluminum compounds on various living systems. The second set, comprised of two papers, deals with the formation and activity of aluminum fluoride compounds. The Volume begins with a chapter by Berend Acute Aluminum Intoxication that outlines the myriad toxic effects aluminum can have once it has by-passed an organisms protective barriers. This occurs in humans, for example, when aluminum salts are used in medicine (a practice that has now been eradicated). The in-depth coverage of this topic provides an excellent background for understanding the chemical interactions associated with aluminum that are described subsequently in Chapters 2-4. 

Mode of action comprises all available information on the toxic effects of a compound. Mechanistic data explain how a chemical interferes with the cellular targets and by that induces toxicity. Such information is essential to understand species specificities, species differences, sensitive populations or the interpretation of data regarding threshold or non-threshold effects. They also help to evaluate the relevance of the toxic effects to humans when the data are derived from experimental animals. 

The main causes of chemical toxicity are side reactions of drug molecules with DNA or proteins, as well as interference with enzymatic systems. There are two databases containing factual toxicological information. One is the RTECS (Registry of Toxic Effects of Chemical Substances), with data on 100 000 compounds. The other is the TOXSYS, with data on 240 000 compounds. ... 

Table 1, compiled predominately from the Jieg/.rtry of Toxic Effects of Chemical Substances database [Canadian Centre for Occupational Health and Safety (CCOHS), 2004], summarizes some LDjqs for various compounds and species exposed via different routes, with the most. sensitive (lowest LDjo) species and route listed accordingly. The LD50, of course, depends on the compound in question, as is illustrated for rats exposed orally to 10 different compounds. It is generally accepted that birds are extremely... 

RTECS Registry of Toxic Effects of Chemical Substances (five-volume NIOSH compilation listing the toxicity data of more than 80,000 compounds no longer published in book format, only available in CD-ROM)... 

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