Toxicity Testing

ReProTect is a project within the 6th European Framework Program which has developed alternative methods aimed to reduce or replace animal experimentation in the field of reproductive toxicology. In its final year, a ring trial, named the “Feasibility Study”, was conducted, in which 10 blinded chemicals with toxicologically well-documented profiles were analyzed by employing a test battery of 14 in vitro assays. EC50 (half maximal effective concentration) or equivalent endpoints were determined and the test compounds were ranked relative to chemicals previously assayed in the tests of the battery. This comparative analysis together with a weight of evidence approach allowed a robust prediction of adverse effects on fertility and embryonic development of the 10 test chemicals in vivo. In summary, the vast majority of the predictions made based on the in vitro results turned out to be correct when compared to the whole animal data. The procedure used here, a nearest neighbor analysis coupled with a weight of evidence approach, may guide future activities in the field of alternative toxicity testing.

Cladocerans have long been used for toxicological assessments of a diverse range of substances. The use of cladocerans in toxicity tests has many advantages, such as their short life cycle, parthenogenetic reproduction (clones), and high sensitivity to toxicants, as well as the easy laboratory maintenance of cultures. The most commonly used cladoceran in ecotoxicological studies of aquatic environments is undoubtedly Daphnia magna. Standard methods using cladocerans as test organisms have been documented and adopted by major international organizations and regulatory agencies of many countries. However, today there is a growing need for improving test organisms and protocols to better reflect local species sensitivity or site-specific conditions. The present study aimed to assess the tropical species Pseudosida ramosa as a potential test organism for ecotoxicological purposes, by carrying out standard acute tests with six reference compounds. Based on the results obtained in the present study and in comparison with other cladocerans, it was found that P. ramosa was more sensitive than Daphnia magna, had a sensitivity similar to that of Daphnia similis, and was less sensitive compared to Ceriodaphnia dubia and C. silvestrii (Neotropical species), except for the salts, sodium chloride and potassium chloride. Also, when P. ramosa was compared with test organisms of other taxonomic groups, we observed that it was more sensitive than most of the others, from simple coelenterates to complex fish. Considering these results and the wide distribution of the cladoceran P. ramosa in tropical and subtropical regions, we suggest that this species can be adopted as a test organism, being a good substitute for the exotic daphnid D. magna, for monitoring of toxicants in freshwaters.

This work aims to evaluate the feasibility of using imidazolium ionic liquids (ILs) in the design of multiphase bioreactors for the removal of volatile organic compounds (VOCs). The IL affinity for three model VOCs (dimethyl sulfide, dimethyl disulfide and toluene) was evaluated by ...

... DOI: 10.1177/0734242X9601400105 1996 14: 43 Waste Manag Res Ege Egemen and Coskun Yurteri Regulatory Leaching Tests for Fly Ash: a Case Study Published by: ... REGULATORY LEACHING TESTS FOR FLY ASH: A CASE STUDY Ege Egemen and coskun Yurteri ...

The ecotoxicity of lactic acid, its alkyl esters and selected metal salts was studied experimentally with the micro alga Selenastrum capricornutum, the crustacean Daphnia magna and the fish species Brachydanio rerio and Pimephales promelas. In addition, the biodegradation of lactate esters was also studied. The aim of the study was to provide predicted environmental data for additional alkyl homologues and metal salts. The ecotoxicity data are evaluated by means of Structure Activity Relations (SAR), using literature data on a nonpolar narcotic mechanism of toxicity as a baseline for comparison. Lactate salts were evaluated by comparison to the toxicity of the metal ion. For the fish and D. magna, it was evident that methyl, ethyl, propyl and to a lesser extent butyl lactate were slightly more toxic in comparison to baseline non-polar narcotic toxicity data. The toxicity tests carried out with lactate-salts demonstrated clearly that the toxicity in standard tests is only determined by the associated cation and not by the lactate part.Lactic acid and its alkyl esters were degraded for more than 60% in the ready biodegradability tests and from the data presented, it is evident that the majority of alkyl lactates are readily biodegradable.The results presented in this study indicate that alkyl lactate esters show some differences in their ecotoxicity when compared to non polar narcotic compounds in but that these differences are generally small. When aquatic toxicity is considered together with their rapid tendency to biodegrade, it is concluded that lactate esters show generally favourable environmental characteristics.

The toxicities of two heavy metals, copper (Cu2+) and chromium (Cr6+), to barley (Hordeum vulgare L.) were evaluated using two types of substrates: artificial and natural forest soils. Phytotoxicity was assessed using a standardized toxicity test. Endpoints included plant emergence and shoot and root growth. Shoot and root concentrations of Cu and Cr were also measured. Data indicated that the root biomass was the most sensitive endpoint. The results showed that toxicity of Cr to root growth (IC50=6.6 μg/g in artificial soil; IC50=61.8 μg/g in forest soil) was higher than that of Cu (IC50=13.7 μg/g in artificial soil; IC50>322 μg/g in forest soil). Data also indicated that the toxicity of Cu and Cr was significantly decreased in the spiked forest soil, suggesting lower metal bioavailability to barley in the natural soil. Analysis of tissue concentrations in barley showed that Cu and Cr were mainly accumulated in the roots. Toxicity was correlated with Cr residues in shoots (⩽11.2 μg Cr/g and ⩽5.3 μg Cr/g for artificial and natural soils, respectively) and roots (⩽161 μg Cr/g and ⩽51.7 μg Cr/g for artificial and natural soils, respectively) and Cu residues in roots (⩽61.8 μg Cu/g and ⩽91.3 μg Cu/g for artificial and natural soils, respectively). Cu concentration in shoot tissues was ⩽61.8 μg Cu/g. Since it may overestimate toxicity, effect and risk assessment using spiked soils, particularly in artificial soil, must be used with diligence.

A working party, comprising two animal welfare organisations and some 12 pharmaceutical companies in Europe, was established to minimise the use of the dog in safety testing. As first step, the participants defined the major objectives of preliminary dose-range finding/MTD toxicity studies in non-rodents, defined the principles and requirements for this study type and agreed on a proposal for an optimised study design, based on collective experience of conducting such studies in industry, involving an evaluation of 100 individual study data sets. The suggested study design is explained and described, and reflects current best practice in the pharmaceutical industry in Europe. The implementation of such an optimised design is believed to result in a reduction in the overall numbers of animals used for this purpose, without jeopardising the scientific rationale and usefulness of the studies for informing the conduct of later regulatory studies.