Substance toxicity evaluation parameters

The parameters below come either from animal experiments or epidemiological 

Lethal concentration 50 (LC50) is the vapour concentration of a substance in air, which kills 50% of the animals exposed. This estimate comes from a protocol that was statistically controlled. This value depends on the animal chosen for the experiments and exposure time. The three animals that are most commonly used are in descending order rat, mouse and rabbit. It is a parameter that estimates risk level by inhalation, which is the most important means of penetration involving toxic substances in the work place. 

The units are preferably ppm (parts per million in volume) for LC50 mg/l for gas and vapour mg/m3 or g/m for aerosols or non-volatile solids that can form suspensions in air. For gas and vapour mg/l is used for the reason that will be explained later. For LD50 use of mg/kg is customary. It goes without saying that the animal genus must be named in all cases. 

There are variants that need to be added to these parameters which can hardly be used at a non medical level. These are minimum toxic doses or concentrations and minimum iethai concentrations or doses (MLC, MLD). The last two are mentioned without using them later on, but given the important level of error regarding LC and LD50 measurements, MLC and MLD can nevertheless be used as a reference. 

These last values are the only ones available for humans. In this case these are the lowest values published following accidents. After collecting these values it was decided not to keep them in the tables after realising that they were useless in the context of this book. 

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The most difficult problem of risk evaluation linked to chemicals will be discussed in this Part. This is primarily a medical problem, which therefore comes within the competence of the company medical officer and epidemiologists, but neverthel need not only be dealt with by them. The person in charge of safety control in a place where chemicals are handled also has to tackle this problem. This person will have to take into account the level of toxicity risk of a substance. This will determine the constraint level of the measures to be taken, its favoured means of penetration, which depends on the activity, and its penetration properties specific to the organism. The physical properties of the substance (which will determine the nature of the precautions to be taken) and also the values of toxicity parameters have to be taken into account. He has to check the container labelling and know how to interpret and explain the toxicity instructions on this labelling. 

The physico-chemical properties may provide indications about the absorption of the substance for various routes of exposure and may therefore be of importance in the evaluation whether an appropriate administration route has been applied in the available experimental toxicity studies. In order for a substance to be absorbed, it must cross biological membranes. Most substances cross biological membranes by passive diffusion. This process requires a substance to be soluble both in lipid and water. The most useful parameters providing information on the potential for a substance to diffuse across biological membranes are the logPoctanoi/water and the water solubility. 

The standard repeated dose toxicity guidehne studies include a number of parameters relevant for the evaluation of a substance s immunotoxic potential. While some information on potential immunotoxic effects may be obtained from the evaluation of hematology, lymphoid organ weights, and histopathology in these studies, there are data which demonstrate that these endpoints alone are not sufficient to predict immunotoxicity. In addition to these standard studies, the US-EPA has developed a specific test guideline for immunotoxicity testing in rodents (OPPTS 870.7800). This... 

The standard repeated dose toxicity guideline studies include a number of parameters relevant for the evaluation of a substance s neurotoxic potential. In addition to these standard... 

Without doubt, the favored field of application of microbial sensors is the measurement of complex effects like sum parameters. The difficulties involved in analyzing the numerous substances that are present in wastewater samples make sum parameters an indispensable part of the wastewater monitoring systems. Additionally, sum parameters often allow a better evaluation of the status of the environment than the determination of the concentration of individual substances. Examples for complex parameters are the sum of biodegradable or bioavailable compounds and toxicity (BOD, ADOC). 

The primary aim of the Irwin Test, first described in the mouse by Irwin (1968) but easily adapted to the rat, is to evaluate the qualitative effects of the test substance on behavior and physiological function, from the first doses that have observable effects up to doses which induce clear behavioral toxicity or even death. The Irwin Test also permits a reasonable estimate of the test substance s duration of action on the different parameters observed. 

Each evaluation should conclude with a summary of the risk posed by a substance. The summary can consist of background information on the chemical and toxicological parameters of the agent human exposure information a summary of the male and female reproductive toxicity data and the developmental toxicity data a list of the quantitative values derived from the data a description of the default assumptions and UFs used in the process the data needs to reduce uncertainty and a reference section. 

Evaluation of neurotoxicity of a chemical substance is dependent on several parameters—for instance, changes in neurochemistry, anatomy, physiology, and or the behavior of the poisoned animal or human. Also, alterations in sensory processes such as paresthesia and visual, olfactory, and or auditory impairments have been often indicated as symptoms of neurotoxicity observed among workers exposed to different toxic substances in workplaces. ... 

Teratogenic effects of substances on test animals are evaluated from resorption (death of the conceptus), fetal toxicity (reduced body weight), aberrations (malformations), and minor anomalies. Statistical analysis is performed by surveying the four most important parameters namely, the number of litters with malformed fetuses, increase in the average number of fetuses with defects per litter, the number of resorptions, and dead fetuses. Finally, the incidence of malformation (response) is plotted against doses administered. Any dose-response relationship should indicate the teratogenicity of the chemical under experimental conditions. 

Knowledge of the bioavailability and absorption rate of an active substance is important because these are important determinants of efficacy and safety. Large variations in bioavailability or absorption rate may, in the case of decreased absorption (rate), result in insufficient efficacy. In the case of unexpectedly high absorption it may lead to toxicity or serious adverse effects. Quantitative data on the bioavailability and absorption rate are necessary to evaluate the equivalence or non-equivalence between different medicinal products with the same active substance. These data may be used as surrogate parameters to establish efficacy and safety of a (generic) product. 

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