Guidelines For Testing Of Chemicals Research Articles

Acute toxicological impact of nano- and submicro-scaled zinc oxide powder on healthy adult mice

In this work, the acute oral toxicity of 20- and 120-nm ZnO powder at doses of 1-, 2-, 3-, 4-, 5-g/kg body weight was evaluated referred to the OECD guidelines for testing of chemicals. As the results, both 20- and 120-nm ZnO belong to non-toxic chemicals according to the Globally Harmonized Classification System (GHS) for the classification of chemicals. The distribution determination showed that Zn was mainly retained in the bone, kidney and pancreas after 20- and 120-nm ZnO administration. However, the results of blood measurement suggest that the increase in blood viscosity could be induced by low and median dose of 20-nm ZnO but high dose of 120-nm ZnO. The pathological examination showed that the 120-nm ZnO treated mice had dose–effect pathological damages in stomach, liver, heart and spleen, whereas, 20-nm ZnO displayed negative dose–effect damages in liver, spleen and pancreas. Therefore, we conclude that the liver, spleen, heart, pancreas and bone are the target organs for 20- and 120-nm ZnO oral exposure. More attention should be paid on the potential toxicity induced by low dose of 20-nm ZnO oral exposure.

A two generation reproductive toxicity study with curcumin, turmeric yellow, in Wistar rats

The reproductive toxicity of curcumin, turmeric yellow, in Wistar rats was studied in order to generate additional relevant toxicity information for the use of curcumin in humans by oral administration. The two generation reproduction study was designed and conducted in accordance with OECD Guideline No. 416 [OECD, 1983. Guidelines for Testing of Chemicals, Guideline No. 416. Two Generation Reproduction Toxicity Study, adopted on 26th May 1983] and in compliance with Good Laboratory Practices (OECD, 1997 Principles of Good Laboratory Practice for the Testing of Chemicals. OECD, C(97)186/Final). The curcumin, mixed in the experimental diet at the concentrations of 1500, 3000 and 10,000 ppm was fed to three groups of rats, i.e., low, mid and high dose groups, and studied for two successive generations. A concurrent control group received experimental diet without the curcumin mixture. There were no treatment related adverse toxicological effects in the parental animals. No gross or microscopic changes were observed in any of the organs. None of the reproductive parameters were affected and there were no effects on the offspring other than a small reduction in pre-weaning body weight gain of the F2 pups at the highest dose level. It was concluded that the no observed adverse effect level (NOAEL) for reproductive toxicity of curcumin, fed in the diet for two successive generations to rats in this study was 10,000 ppm, which is equivalent to 847 and 959 mg/kg bodyweight (bw) per day for male rats and 1043 and 1076 for females for F0 and F1 generations, respectively. This study was the final toxicology study on curcumin reviewed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) at the 61st Meeting, 2003. The JECFA group considered that the small body weight reduction in the F2 pups of the highest dose group prevented this from being regarded as a no adverse effect level, and so allocated an ADI for curcumin of 0–3 mg/kg bw based on the intake of 250–320 mg/kg bw in the mid-dose group as the NOEL.

Comments on A Scientific and Animal Welfare Assessment of the OECD Health Effects Test Guidelines for the Safety Testing of Chemicals Under the European Union REACH System

Comments on <i>A Scientific and Animal Welfare Assessment of the OECD Health Effects Test Guidelines for the Safety Testing of Chemicals Under the European Union REACH System</i>

ＯＥＣＤガイドラインにおける動物福祉

The OECD established the Guidelines for Testing of Chemicals in 1981, which is the basis of the mutual acceptance of data (MAD) system among the member countries to prevent unnecessary repetition of toxicity tests, and consequently to reduce the number of animals used. The Guidelines was soon subjected to revision from the viewpoint of animal welfare besides its periodical updating with the state-of-art in the toxicological sciences. Revision of the Test Guidelines is in progress according to the 3Rs principle, reduction, refinement and replacement. The acute toxicity test and the skin and eye irritation/corrosion tests were assumed to be the most problematic ones among the animal tests in animal welfare aspect. Three different test methods have been adopted for the alternative to acute oral toxicity test (Test Guideline (TG) 401), namely, the fixed dose procedure (TG420), acute toxic class method (TG423) and up-and-down procedure (TG425), and the reduction of animals was accomplished. Then the traditional acute oral toxicity test (TG401) has been deleted from the Guidelines. Procedures for irritation/corrosion tests for skin (TG404) and eye (TG405) were reorganized into tier-test system in order to prevent any corrosion or strong irritation to take place. The tier system consists of survey of toxicities of the test chemical, structure-activity relationship, pH, and testing with in vitro methods. Moreover, at the final tier animal testing should proceed by one animal. Three kinds of in vitro corrosivity tests have been adopted in the Guidelines.

A Scientific and Animal Welfare Assessment of the OECD Health Effects Test Guidelines for the Safety Testing of Chemicals under the European Union REACH System

We have assessed each of the OECD Health Effects Test Guidelines (TGs) that were included in an annex to the Internet consultation issued by the European Commission relating to the Registration, Evaluation and Authorisation of Chemicals (REACH) legislation for the testing of new and existing chemical substances. Each guideline has been analysed with respect to its design and its scientific and animal welfare implications, the extent to which it makes use of modern techniques, and its suitability to be used in the REACH system for the testing of large numbers of chemicals. The scientific basis of the test and its justification are considered, as well as the numbers of animals required, and the potential adverse effects on them. The prospects and possibilities for applying the Three Rs (reduction, refinement and replacement) to each of the TGs are also discussed. We have proposed an overall testing strategy for how these TGs and other methods could best be deployed for chemicals testing, should it be necessary to fill data gaps. Certain TGs have been omitted from the strategy, when we have considered them to be unnecessary for chemicals testing. A series of recommendations has been made for improving the TGs with regard to both their scientific content and ways in which they could be better designed in relation to optimising the use of the animals concerned, and minimising adverse welfare consequences to them. Our investigations show that there is an urgent need to update the TGs to reflect modern techniques and methods, and to use current approaches for applying refinement strategies to improve the scientific and animal welfare aspects of the procedures used. Improvements can and should be made in all aspects of toxicity testing, from sample preparation, and animal housing, care and feeding, to dose formulation, test material administration, and the histopathological and clinical analysis of tissue samples. Opportunities for streamlining individual assays are very limited, but testing could be made more efficient by: a) only undertaking studies that provide relevant data; b) making greater use of screens and preliminary testing; c) applying some tests simultaneously to the same animals; d) using one sex; and e) eliminating redundant tests. In conclusion, it is clear that, as they stand, the OECD Health Effects TGs are unsuitable for use in the European Union REACH system, for which potentially very large numbers of laboratory animals will be needed for the testing of a very large number of chemicals.

Environmental risk assessment scheme for plant protection products

Environmental risk assessment scheme for plant protection products

Comparative Evaluation of Effects of .GAMMA.-Rays and Heavy Metals on Mobility of the Water Flea Daphnia magna

The authors comparatively studied effects of γ-rays and some heavy metal treatments on mobility of water flea Daphnia magna according to the OECD Guideline for Testing of Chemicals, which is generally used for ecotoxicity evaluation of chemicals. The 50% effect dose at 24 hours after γ-irradiation (ED50/24h) was 1 600 Gy. The 50% effect concentrations following 24 hours exposure for manganese, nickel and copper (EC50/24h) were 990, 180 and 3.3 μM, respectively. The Gy-equivalent factors (=ED50/24h/EC50/24h) were therefore calculated as 1.6, 8.9 and 480 for manganese, nickel and copper, respectively. These factors indicate that toxicity of these metals to D. magna can be ranked in an order of Mn<Ni<Cu. This toxicity rank shows a similar trend to that evaluated previously in the experimental model ecosystem (microcosm) consisting of three species of aquatic microorganisms. However, there was a noteworthy difference in the toxicity ranks obtained from the D. magna immobilization test and the microcosm test, suggesting that ecotoxicity ranking should be carried out by integrated evaluation on the basis of various ecotoxicity tests.

One-generation reproduction toxicity study of Dithane M-45 (mancozeb) and lead acetate.

The reproductive toxicity of lead acetate and of a fungicide formulation (Dithane M-45) containing 80% mancozeb was studied on rats. Lead acetate was applied in the feed in the following dose groups: control, 1,000, 5,000 and 10,000 mg/kg of diet. The three treatment groups received, in addition to the above doses of lead acetate, 4,500 mg/kg Dithane M-45 in the diet. The method was based on the OECD Guideline for Testing of Chemicals No. 415 (1981). Clinical symptoms and mortality were not found in the parent generation. The body weight of female animals decreased significantly before the pregnancy period. This tendency was also seen in males after the combination treatment. At the two high dose levels a remarkable body weight increase was seen in the female animals during the lactation period. As a result of treatment, decreased body weight of offspring was measured during the lactation period. No gross pathological changes were seen. Histological examination showed general tubulonephrosis in the experimental animals. It can be established that the administration of Dithane M-45 did not enhance the reproductive toxicity of lead acetate.

Genotoxicological effects of some phenoxyherbicides and their metabolites on Bacillus subtilis M45 Rec − and H17 Rec + strains

Because they are used in a number of commercial preparations phenoxyacetic acids and their salts can occur in wastewater. During their degradation genotoxic substances may be created. The results of investigations of biodegradability and genotoxicity of some phenoxyherbicides are presented. Commercial formulations of 2,4-D (Aminopielik 720) and MCPA (Chwastox Extra) were the substrates studied. Biodegradation tests were conducted according to OECD guidelines for testing of chemicals – confirmatory test (OECD Method 303 A). Genotoxicity tests were conducted with Bacillus subtilis strains according to the method of [Chemical Mutagens, vol. 6, Plenum Press, New York, 1980, p. 149]. Genotoxicity of biodegradation products was also studied. Both commercial formulations were biodegradable. Aminopielik 720 was potentially genotoxic but only at great concentrations while Chwastox Extra was not genotoxic. Biodegradation products of neither compound were genotoxic.

Validation of pH-Metric Technique for Measurement of pKaand log Powof Ionizable Herbicides

Abstract Knowing the values of pKa and partition coefficients between 1-octanol and water (Pow) of ionizable herbicides helps us to understand the movement of these compounds in plants and soil. However, shake-flask and high-pressure liquid chromatography (HPLC) techniques. though valuable for measurement of log Pow of herbicide molecules that do not ionize in aqueous solution, are difficult to use for ionizable molecules; this is especially so for molecules that form ion pairs having appreciable log Pow values, those with multiple ionizations and for bases with high pKa values. Our aim in this study was to validate the use of the pH-metric technique (based on potentiometric titration) for measurements of pKa and log Pow of ionizable standard substances and herbicides. The values obtained show good correlation with results from other techniques, including shake-flask and HPLC. The OECD Guideline for Testing of Chemicals 117, adopted 30th March 1989, describes the use of HPLC for the measurement of log Pow...

The combined CO 2/DOC test - a new method to determine the biodegradability of organic compounds

The OECD Guidelines for Testing of Chemicals (OECD, 1993) offer a variety of methods to determine the biodegradability of chemical compounds. The determination of the ready biodegradability, in particular, plays a crucial role in the ecological characterization of substances. Nevertheless, for the methods based on DOC removal it is difficult to differentiate clearly between physical/chemical elimination and microbial degradation. Therefore, the combined CO 2/DOC test was designed, which offers the opportunity to simultaneously follow the DOC removal and mineralization of a compound. The new method was optimized with regard to the properties of the medium and inoculum concentration and compared with the manometric respirometry test (OECD 301 F) and the Zahn-Wellens test (OECD 302 B). The results obtained show that the combined C0 2/DOC test provides reliable results and gives enhanced information on the biodegradation pattern of a chemical compound.

Relevance of endpoints in toxicity testing of food ingredients

the testing of food ingredients like food additives for potential toxicity, the guidelines published by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) (IPCS, 1987) and Scientific Committee for Food (SCF) of the EEC (EEC, 1980) provide a general outline. OECD guidelines for testing of chemicals (OECD, 1981) give more details about the actual testing and the parameters to be used, It is, however, evident that the endpoints specified in the OECD guidelines may not always be completely appropriate for providing relevant information about the safety of a food ingredient. This is especially the case when the guidelines are used in the testing of major food ingredients, for example bulk sweeteners, bulking agents, fat replacers and other macro-ingredients. Recently, two papers have discussed weaknesses in the way food toxicology has developed (Conning, 1987; Roe, 1987). Among Roe's conclusions the following should be noted: The present custom is to conduct carcinogenicity tests in animals under conditions of overnutrition. such tests, high incidences of tumours in control animals confuse the interpretation of the results, increasing the chances that both false negative and false positive results will be obtained. Superimposed on this confused background there may be imposed requirements by regulatory authorities to test food ingredients at concentrations vastly in excess of those that would be encountered in nature. Similarly, Conning has a critical conclusion: In essence, the future of food toxicology is in the field of nutritional toxicology and particularly in relating diet to degenerative diseases. conventional approach to toxicity testing based upon large-scale animal experimentation has not only impeded the development of toxicology as a science but has priced itself out of the market as far as food chemicals are concerned. development of new techniques directed more specifically at human effects and related to known human diseases promises to bring initially closer together the studies of toxic mechanisms and the biochemical basis of human disease both centred on intracellular aberrations. A somewhat more cautious, but constructive criticism has come from JECFA itself (IPCS, 1987):

Toxicity and QSAR of chlorophenols on daphnia.

Toxicity of phenol and 7 chlorophenols from mono-Cl to penta-Cl on 3 species of daphnia, Daphnia magna, Daphnia carinata and Daphnia pulex has been determined according to OECD guideline for testing of chemicals. The responses of each daphnia to chemicals were measured by acute immobilization of young daphnia less than 24 h old (24 h-EC50) and reproduction inhibition during 14 d (14 d-Maximum Acceptable Toxicity Concentration, MATC). The 24 h-EC50 values were correlated with 6 physico-chemical parameters of chlorophenols. The parameters employed in this quantitative structure-activity relationship (QSAR) analyses were : n-octanol/water partition coefficient, log POW ; dissociation constant, pKa ; Hammett Σσ constant ; index of valence molecular connectivity, 1χV ; perimeter of the efficient cross section of molecule, ΣD ; melting point, mp. In immobilization studies, 24 h-EC50 values of each daphnia decreases as substituted chlorine atom increases and QSAR study shows that log POW, a parameter of hydrophobicity, gives the best correlation. Toxic responses of 3 kinds of daphnia are almost the same each other and 24 h-EC50 value of each chlorophenol is almost the same as 96 h-LC50 in fish, P. reticulata. On the other hand, in the reproduction inhibition study using Daphnia magna, MATC values of mono-, di-, tri-, tetra- and pentachlorophenol are almost the same each other and no relationship was found between MATC values and substituted chlorine numbers.

Chemicals programme in OECD.

The Organisation for Economic Co-operation and Development (OECD) is an inter-governmental organisation which is composed of 24 industrialized countries in the western bloc. OECD aims at attaining economic growth in Member countries in terms of not only quantity but also quality. One of the important aspects of quality is protection of environment. OECD has made several achievements in the international control of chemicals, e.g., consolidated actions for PCBs, mercury and cadmium, Guidelines for Testing of Chemicals, Principles of Good Laboratory Practice (GLP), Minimum Premarketing Set of Data (MPD). The present work in OECD focuses on existing chemicals for which international co-operations are strongly needed in light of the number of chemicals and the size of necessary work for them. This article outlines the achievements and the present work of the Chemicals Programme in OECD.

Current OECD activities relating to the Hazard Assessment of Chemicals

The OECD Hazard Assessment Project was initiated by the Chemicals Group in December 1979, a time when the early phase of the OECD Chemicals Programme was essentially drawing to an end with major products such as draft Guidelines for Testing of Chemicals and the Minimum Pre-marketing set of Data (MPD). MPD constitutes a package of data which would normally be sufficient to allow a meaningful first assessment of the potential hazard of a chemical at the premarketing stage. It was thought important, once MPD had been proposed, to start a hazard assessment project based on MPD. In fact, the Expert Groups which developed the draft Test Guidelines had in many cases discussed principles for interpretation of test results-with respect to individual MPD parameters, but also integrated interpretation of such parameters. OECD has been working with chemicals control since the beginning of the 1970s. Initially, actions within the Organisation were concentrated on individual chemicals such as mercury and PCBs, but soon questions about testing and assessment of chemicals in general became the major target of the work. The somewhat limited scope of the OECD Hazard Assessment Project and the national and international needs which constitute the driving force for such a Project will be discussed. But first I would like to stress that in its Chemicals Programme OECD has always attempted to use the best available science as a basis for its policy actions. Therefore, it is with great interest that the Organisation follows activities such as the present symposium, so timely convened by IAES and SECOTOX. I am confident that the experts gathered here in London have added substantially to our knowledge of the current scientific basis for hazard assessment, and that the OECD Project will benefit from this. Initially, the work under the Hazard Assessment Project is being carried out in