Evaluation of Toxicity

Hbso concentration causing 50% lysis of human erythrocytes. 

IC50 concentration causing 50% loss of viability of mouse peritoneal macrophages, using the MTT test, after the incubation times stated. 

LD50 acute toxicity assessed in CDl male mice after a single intravenous bolus injection. Values are calculated from the number of mice surviving the injection. 

AmB formulations were dispersed in phosphate-buffered saline (PBS) at different concentrations (0.1 lOOpg/mL) and incubated for five minutes at 37°C. Freshly isolated human erythrocytes were then added to a final hematocrit of 2% and incubated at the same temperature for 30 minutes. After centrifugation, the supernatant was removed and the RBC pellet was lysed with sterile water. The hemoglobin remaining in the pellet was estimated from its absorption at 560 nm recorded with a spectrophotometer. The percentage hemolysis was calculated from the difference between the hemoglobin remaining in the test samples and the control incubated with PBS alone. 

AmB solubilized in DMSO and dispersed in PBS provoked 50% hemolysis of human erythrocytes at 3.5mg/L of AmB. Fungizone and AmB prepared by the same process as LC-AmB but without lipids were slightly less toxic (Hbso 5mg/L). All the lipid formulations caused less than 50% hemolysis at the highest concentration tested (lOOmg/L). 

Solvents used to increase solubility for compounds during screening of permeability across the cell monolayers, together with commonly used excipients for formulations, can also affect the barrier as they contain ingredients which enhance drug absorption [100, 151]. There are different mechanisms by which these compounds can modulate the barrier [4, 149, 150] for example, they may increase the tight junctional pathway inhibiting carrier-mediated transport, or cholesterol 

A lowering of the permeability coefficients of compounds has been reported during the screening procedure using cell monolayers and commonly used excipients [98] (e.g., using PEG 400, DMSO), and it is also known that both DMSO and ethanol affect the general metabolic capacity of the cells, leading to an overestimation of permeability [156], 

By observing human, animal, or plant populations exposed to a chemical (epidemiology) 

By administering the chemical to animals or plants under controlled conditions and observing the effects (in vivo) 

By exposing cells, subcellular fractions, or single-celled organisms to the chemical (in vitro) 

Data obtained from human exposure or clinical trials is analyzed by epidemiological techniques. Typically, effects observed will be compared with those in control subjects with the objective of determining if there is an association between exposure to the chemical and a disease or adverse effect. 

Cohort studies in which individuals exposed to the chemical of interest are followed overtime prospectively. This design is used in clinical trials of drugs. Controls are subjects selected out of the patient population and have the disease for which the drug is prescribed. The controls receive an inactive placebo.  

---

Reproducibility evaluation of toxicity test of phenylmercuric nitrate 187... 

Savarie, P.J. and R.T. Sterner. 1979. Evaluation of toxic collars for selective control of coyotes that kill sheep. Jour. Wildl. Manage. 43 780-783. 

Borrell, A., A. Aguilar, S. Corsolini, and S. Focardi. 1996. Evaluation of toxicity and sex-related variation of PCB levels in Mediterranean striped dolphins affected by an epizootic. Chemosphere 32 2359-2369. 

Table 2 Ranges of acute toxicity (pg/L) of SPs to fish, various groups of aquatic invertebrates, and algae (Giddings JM (2006) Compilation and evaluation of toxicity data for synthetic pyrethroids. Unpublished report of Compliance Services International, Rochester)...

JM (2006) Compilation and evaluation of toxicity data for synthetic pyrethroids. Unpublished report of Compliance Services International, Rochester). 

Health hazards caused by chemicals are represented by the Toxic Exposure Subindex (ITox). hi the ISI the evaluation of toxic exposure is based on the Threshold Limit Values (TLV) because TLV data is readily available for most substances in process industry. TLV values express the harmful exposure limits of substances in the threshold time of 8 hours. The index value is higher, when the TLV is lower i.e. the substance is more toxic. It is important to use TLVs with same threshold time so that the results are comparable. Score limits in Table 13 are based on Mond Index (ICI, 1985). 

Landis WG, Matthews RA (1993) Development of pattern recognition techniques for the evaluation of toxicant impacts to multispecies systems. Government Reports Announcements Index (GRA I) Issue 21 NTIS/AD-A267 197/2, p 255... 

Steidinger, K., A re-evaluation of toxic dinofiagellates biology and ecology, in Round, F. and Chapman, D., eds.. Progress in Phycological Research, Elsevier, Amsterdam, 1983. 

Different animal species exhibit differences in GI absorption rates. The extent of GI absorption of lead in rats, for example, can be studied by feeding the animals known amounts of the metal and analyzing the unabsorbed amount that comes through in feces the difference is the amount absorbed. But because of possible species differences it is not possible to conclude that humans will absorb the same amount of lead as the rat. These types of differences complicate evaluation of toxic potential. At the same time, they help to explain why different species of animals respond differently to the same dose of a chemical. 

Irritation is veiy subjective and may differ widely from treatment to control subjects. Most irritation occurs as a result of penetration enhancers. Evaluation of toxicity and irritation should be concerned with mucosal tissue irritation, the extent of damage to the mucosal cells, and the rate of recovery. 

Evaluation of Toxic After detonation Gases Formed by Industrial Explosives. Translation of the tide of paper by A.G. Streng in Ex-plosivstoffe 19, March/April. 1971, pp 58—64. Abstracted in Expls St Pyrots 5(8)(1972)... 

Evaluation of toxic afterdetonation gases formed by industrial explosives 6 E346... 

Evaluation of Toxic Effects of Organic Contaminants in Recycled Water EPA. U.S. Government Printing Office Washington, DC, 1978. 

Ocular damaging and irritant agents can be identified and evaluated by the Draize rabbit test [114]. However, more recently this test has been criticized on the basis of ethical considerations and unreliable prognosis of human response. Alternative methods such as the evaluation of toxicity on ocular cell cultures have been recommended and are being indicated as promising prognostic tools [115-120]. Direct confocal microscopic analysis [121], hydration level of isolated corneas [122], and various other tests on isolated corneas or animal eyes have also been proposed for evaluation of ocular toxic effects. 

Data from all long-term animal studies are considered in the evaluation of toxicity. A positive response in one species/strain/ sex is not generally negated by negative results in another species/strain/sex. However, replicate negative studies that are essentially identical to a positive study may indicate that the positive results are spurious. 

Erten-Unal, M., Wixson, B.G., Gale, N. and Pitt, J.L. (1998) Evaluation of toxicity, bioavailability and speciation of lead, zinc and cadmium in mine/mill wastewaters, Chemical Speciation and... 

Gagne, F., Blaise, C., van Aggelen, G., Boivin, P., Martel, P., Chong-Kit, R., Jonczyk, E., Marion, M., Kennedy, S.W., Legault, R. and Goudreault, J. (1999a) Intercalibration study in the evaluation of toxicity with rainbow trout hepatocytes, Environmental Toxicology 14 (4), 429-437. 

Novak, L.J., Holtze, K.E. and Roy, R. (1998) Evaluation of Toxicity Reduction Evaluation (TRE) and Toxicity Identification Evaluation (TIE) application to the Canadian mining industry, AETE Report No. 1.2.5. Prepared by ESG International Inc. 

Komori K, Nada J, Nishikawa M et al (2009) Simultaneous evaluation of toxicities using a mammalian cell array chip prepared by photocatalytic lithography. Anal Chim Acta 653(2) 222-227... 

The acute dermal irritation is the study of reversible inflammatory changes in the skin of test animals following the application of a test chemical. Acute dermal corrosion is the study of irreversible tissue damages in the skin following the application of a test chemical. In the evaluation of toxic characteristics of a chemical, determination of the irritant or corrosive effects on mammal skin is an important study step. Information derived from this test indicates the existence of hazards likely to arise from skin exposure to the test chemical. 

In the evaluation of toxic characteristics of an inhalable environmental chemical (e.g., carbon monoxide, volatile chemical, or aerosol/particulate), determination of acute inhalation toxicity is an initial study step. It provides information on health hazards likely to arise from short-term exposure by inhalation. Data from an acute test help to establish a dose regimen in subchronic (and other) studies, and may provide additional information on a chemical s mode of toxic action. 

In the evaluation of toxic characteristics of any environmental chemical, determination of oral toxicity using repeated doses may be performed after obtaining initial acute toxicity data. This provides information on possible adverse effects that may arise from repeated exposures to the test chemical over a limited period of time. Although there are major similarities in the 28-day and 14-day oral toxicity studies on rodents, the main difference lies in the time over which the dose is administered and the extent of the clinical and pathologic investigations that might be necessary for the shorter period of test. 

An integrated testing strategy is any approach to the evaluation of toxicity which serves to reduce, refine or replace an existing animal procedure, and which is based on the use of two or more of the following physicochemical, in vitro, human (e.g., epidemiological, clinical case reports), and animal data (where unavoidable), and computational methods, such as (quantitative) structure-activity relationships ([Q]SAR) and biokinetic models. 

This excellent, 44-page Canadian booklet [18] lists 58 references covering, but not limited to Emergency Planning, Process Hazards Reviews, Fault Tree Analysis, Evaluation of Toxic Vapor Cloud Hazards. 

Mehta, P.K., Sood, A.K., Patial, A. and Lai, R. (2005) Evaluation of toxic and antifeedant properties of some plant extracts against major insect pests of cabbage. Pesticide Research Journal 1 7(2), 30-33. 

Schoeters et al. (1995) evaluated the hematopoietic and osteogenic toxicity of benzene, phenol, hydroquinone, and catechol in vitro using murine bone marrow cultures. Evaluation of toxicity to 3T3-fibroblasts was included to determine specific toxicity to marrow cells. Benzene and phenol showed little effect. However, hydroquinone inhibited proliferation of 3T3 cells and marrow precursor cells, and calcification of bone cells, although it was more specific for marrow cells. Catechol inhibited all cells, and showed no specificity. 

---