Toxicity testing

Characterisation of effects. Assessment of effects comprises the determination of harmful effects as a function of exposure to a toxic chemical. Effects have to be related to the assessment endpoint. Effects may be derived from field studies conducted at the contaminated site (ecological epidemiology) or by performing toxicity tests with the chemical concerned. The latter are used more frequently in effect assessment. 

Risk characterisation. Risk characterisation is a process that integrates results of the analysis phase (exposure and effects) and information pertaining to uncertainty of the estimation and description of risks. Within this phase, the likelihood of the current (diagnostic) or future occurrence (prognostic) of significant effects and their consequences on the assessment endpoint are estimated resulting in an appraisal of the severity and temporal extent of harm to the environmental value. 

Risk management. This is a decision-making process that focuses on the minimisation of risks but is not part of the assessment procedure. However, communication between risk assessors and managers throughout the whole procedure is necessary for an efficient assessment. In the context of contaminated land assessment, a decision has to be taken whether remedial action is required or not. 

It is important to distinguish between assessment and measurement endpoints (Gaudet 1994). An assessment endpoint is an environmental value that has to be protected. If the risk assessment process results in an unacceptable risk for the defined environmental value, then risk reduction measures (e.g. remediation of site) are required. A measurement endpoint is a measurable environmental characteristic, such as the quantitative summary of the results of a toxicity test or a biological survey (Suter 1993). If assessment and measurement endpoints are not the same, it is necessary to constitute a quantitative relationship between these to enable the extrapolation of measured effects to the threatened environmental characteristic. 

Toxicity assessment is the determination of the potential of any substance to act as a poison, the conditions under which this potential will be realized, and the characterization of its action. Risk assessment, however, is a quantitative assessment of the probability of deleterious effects under given exposure conditions. Both are involved in the regulation of toxic chemicals. Regulation is the control, by statute, of the manufacture, transportation, sale, or disposal of chemicals deemed to be toxic after testing procedures or according to criteria laid down in applicable laws. 

A Textbook of Modern Toxicology, Third Edition, edited by Ernest Hodgson ISBN 0-471-26508-X Copyright 2004 John Wiley Sons, Inc. 

Consumer Product Safety Commission Consumer Product Safety Act 

Federal Water Pollution Control Act Safe Drinking Water Act Toxic Substances Control Act Resource Conservation and Recovery Act 

State governments Various state and local laws 

Clinical Side Effect Predictable from Animal Studies (V/x)  

It is important that the identity of the test substance be defined in the first instance. The physical and chemical properties of the drug under test provide important 

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For the sample search on aquatic toxicity of atrazine, 1459 results were found. An excerpt on the daphnia acute aquatic toxicity tests (EC50. LC.50) is prc.scnted in Figure 5-33. 

Acute inhalation exposure of rats to 200,000 ppm VF for 30 minutes or more produced weak anaesthesia and no deaths (90). In rats VF is only slightly metabolized at a rate of one-fifth that of vinyl chloride (91—95). An extensive program of toxicity testing of vinyl fluoride is ia progress (96,97). 

The importance of hydrolysis potential, ie, whether moisture or water is present, is illustrated by the following example. In the normal dermal toxicity test, namely dry product on dry animal skin, sodium borohydride was found to be nontoxic under the classification of the Federal Hazardous Substances Act. Furthermore, it was not a skin sensitizer. But on moist skin, severe irritation and bums resulted. 

Daylight fluorescent pigments (qv) are considered to be nontoxic. Since they are combinations of polymers and dyestuffs, the combined effect of the ingredients must be taken into account when considering the net toxic effect of these materials. Table 5 gives results of laboratory animal toxicity tests of standard modified melamine—formaldehyde-type pigments, the Day-Glo A Series, and the products recommended for plastic mol ding, Day-Glo Z-series. 

Table 5. Results of Laboratory Animal Toxicity Tests...

In heavy-metal analysis of the same pigments, metals found were present in only trace amounts. The data Hsted place the products tested in the category of nontoxic materials. The Radiant Color Co. has conducted toxicity tests on its own products similar to the A-Series and has found them to be nontoxic. Heavy metals were found only in trace amounts in these tests. 

R. Patrick, Report of Toxicity Tests, Academy of Natural Sciences, Philadelphia, Pa., 1951. 

Aquatic Toxicity. The standard tests to measure the effect of substances on the aquatic environment are designed to deal with those that are reasonably soluble ia water. Unfortunately this is a disadvantage for the primary phthalates because they have a very low water solubiUty (ca 50 p.g/L) and this can lead to erroneous test results. The most common problem is seen ia toxicity tests on daphnia where the poorly water-soluble substance forms a thin film on the water surface within which the daphnia become entrapped and die. These deaths are clearly not due to the toxicity of the substance but due to unsuitable test design. 

Based on tests with laboratory animals, aniline may cause cancer. The National Cancer Institute (NCI) and the Chemical Industry Institute of Toxicology (CUT) conducted lifetime rodent feeding studies, and both studies found tumors of the spleen at high dosage (100 —300 mg/kg pet day of aniline chloride). CUT found no tumors at the 10—30 mg/kg per day feeding rates. The latter value is equivalent to a human 8-h inhalation level of 17—50 ppm aniline vapor. In a short term (10-d) inhalation toxicity test by Du Pont, a no-effect level of 17 ppm aniline vapor was found for rats. At high levels (47—87 ppm), there were blood-related effects which were largely reversible within a 13-d recovery period (70). 

Celanese Corp., Tange Finding Toxicity Test on n-Propanol, Industrial Hygiene Foundation of America, Inc., Pittsburgh, Pa., July 1962. 

Threshold limit value (TLV) not estabUshed by ACGIH. Value given is an estimate of a comparable iadex based on limited or incomplete toxicity testing made by chemical producers. 

The health effects of sorbic acid and sorbates have been reviewed (165—167). The extremely low toxicity of sorbic acid enhances its desirabiHty as a food preservative. The oral LD q for sorbic acid in rats is 7—10 g/kg body weight compared to 5 g/kg for sodium chloride (165—169). In subacute and chronic toxicity tests in rats, 5% sorbic acid in the diet results in no abnormal effects after 90 days or lifetime feeding studies. A level of 10% in rat diets results in a slight enlargement of the Hver, kidneys, and thyroid gland (170). This same dietary level fed to mice also resulted in an increase in Hver and kidney weight... 

There are many guidelines that need to be followed and which are common to all types of toxicity testing, the most important of which are as follows ... 

Safety is assessed by subjecting the antioxidant to a series of animal toxicity tests, eg, oral, inhalation, eye, and skin tests. Mutagenicity tests are also carried out to determine possible or potential carcinogenicity. Stabilizers are being granulated and Hquid products are receiving greater acceptance to minimize the inhalation of dust and to improve flow characteristics. 

The toxicity of a few boric acid esters has been summarized (30). In general the toxicities are directiy related to the toxicity of the alcohol or phenol produced on hydrolysis. Methyl borate has an oral rat LD q of 6.14 mL/kg in a range finding test (31) and the percutaneous LD q for the rabbit of 1.98 mL/kg. In eadier work (32), the oral LD q for the rat was 2.82 mL/kg the intraperitoneal LD q was 3.2 mL/kg. It has been shown that the mouse is more susceptible to these compounds than the rat. Methyl borate was found to be moderately irritating in an ocular toxicity test using rabbits (31,32) but only mildly irritating to skin (31). 

The data from some single-dosage oral toxicity tests, expressed as LD q, are reported in Table 4. The values reported on the order of 1 g/kg or greater indicate a low acute oral toxicity. In animals, continued ingestion of chlorobenzenes over a long time can cause kidney and Hver damage. 

Both acute and chronic toxicity testing of the treated effluent on daphnia shrimp and fathead minnows have indicated that the effluent is completely suitable for discharge into receiving waters with no adverse impact (42). 

Mice are utilized for testing antiseptics for appHcation to cuts, wounds, and incisions (339). The test bacteria, type 1 pneumococcus and hemolytic streptococcus, ate appHed to the taHs of anaesthetized mice. The tip of the taH is then dipped into the antiseptic for 2 min, after which one-half inch of the taH is removed and inserted into the peritoneal cavity and the incision is closed. If after 10 days the animals survive, the product is considered satisfactory for use as a skin antiseptic. The blood of dead animals is sampled and streaked on blood agar for confirmation of infection from the test bacteria as the cause of death. Since lack of toxicity is another requirement of a product to be appHed to wounds, this test has been combined with a toxicity test (340). 

Physicochemical properties requked include melting/boiling point, vapor pressure, solubiUty, and flammabiUty/explosion characteristics. The toxicological studies include acute toxicity tests, oral, inhalation, and dermal skin and eye kritation skin sensiti2ation subacute toxicity, oral, inhalation, and dermal and mutagenicity tests. In vitro reverse mutation assay (Ames test) on Salmonella typhimurium and/or E.scherichia coli and mammalian cytogenic test. In vivo mouse micronucleus test. 

EinaHy, the ecotoxicological studies, designed to assess the impact of the substance on the environment, embrace acute toxicity tests to fish and Daphnia, and a battery of tests for the biodegradabiUty of the substance and its biological oxygen demand characteristics. 

Carotenoids have two general characteristics of importance to the food iadustry they are not pH sensitive ia the normal 2—7 range found ia foods, and they are not affected by vitamin C, making them especially important for beverages. They are more expensive than synthetic food dyes and have a limited color range. In their natural environment they are quite stable, but they become more labile when heated or when they are ia solution. Under those conditions, there is a tendency for the trans-double bonds to isomerize to the cis-stmcture with a subsequent loss of color iatensity. The results of controlled tolerance and toxicity tests, usiag pure carotenoids, iadicate that they are perfecdy safe as food colors (132). 

Biological sui veys should be used together with whole-effluent and ambient toxicity testing, and chemical-specific analyses to assess the attainment/nonattainment of designated aquatic hfe uses in state water-quahty standards. ... 

The full extent of the toxicity of pesticides to aquatic life is not known. Although chronic toxicity testing is required for new substances, little is known about the long-term effects of older pesticides. Also, very little is known about the toxicity and occurrence of the products formed when pesticides break down (metabolites) or the many non-pesticidal additives (co-formulants and adjuvants) used in pesticide formulations. However, the future is looking brighter. New modelling techniques, EQS development, and the involvement of the NRA in the pesticide registration process, coupled with the development of newer, less persistent pesticides with lower dose rates, all should help to reduce the risk of pesticide pollution. 

In vitro cytotoxicity assays using isolated cells have been applied intermittently to cyanobacterial toxicity testing over several years." Cells investigated for suitability in cyanobacterial toxin assays include primary liver cells (hepatocytes) isolated from rodents and fish, established permanent mammalian cell lines, including hepatocytes, fibroblasts and cancerous cells, and erythrocytes. Earlier work suggested that extracts from toxic cyanobacteria disrupted cells of established lines and erythrocytes," but studies with purified microcystins revealed no alterations in structure or ion transport in fibroblasts or erythrocytes,... 

Corrective Action Application In Massachusetts, a municipal wastewater treatment plant receives a number of wastestreams containing heavy metals from local industries. When tested, the dewatered sludge failed the EP toxicity test. In order to permit landfill disposal of the sludge, solidification processes were examined. A soluble, silicate-based system, developed by Chemfix, was ultimately selected which produced a product whose leachate passed the EP toxicity test (Sullivan, 1984). 

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