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In this work, a monoclonal antibody called G12, raised against the most immunotoxic peptide to celiac disease patients, was used to develop a sandwich ELISA. Preliminary results on cross-reactivities, recoveries, and extraction methods of the new assay are presented. The assay calibration was performed using material from the Prolamin Working Group. The antibody's specificity was determined by crossreactivity studies on different grains, nuts, oils, and starches. Recovery of the assay was determined by spiking experiments on common food matrixes, as well as on problematic matrixes. Furthermore, sample extraction methods using ethanol, cocktail solution, and a proprietary buffer have been compared.

The validation of alternative methods is a relatively new activity in toxicology. The local lymph node assay (LLNA), a novel method for the identification of chemicals that have the potential to cause skin sensitization, was the first test to pass through the formal regulatory validation process established in the USA under the auspices of ICCVAM, the Interagency Coordinating Committee on the Validation of Alternative Methods. ICCVAM approved the LLNA as an alternative to guinea pig tests for the identification of skin sensitisation hazards. In this report, we explore the nine recommendations made by ICCVAM and discuss their interpretation in relation to the new OECD Guideline 429, which describes the LLNA. In particular, the value and limitations of the use of statistical evaluation of data and of the inclusion of routine positive controls is examined. It is concluded that the OECD Guideline as currently written embodies the necessary flexibility to permit conduct of the LLNA in a manner necessary to meet the varying needs of regulatory agencies and toxicologists around the world.

The UK Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (COC) and the related Committee on Mutagenicity provided advice on 1,3-butadiene in 1992. This followed detailed consideration of the available mutagenicity, animal carcinogenicity and epidemiology data plus information on toxicokinetics. They concluded that 1,3-butadiene was an in vivo mutagen, a potent genotoxic animal carcinogen and should be regarded as a probable human carcinogen. The Department of Health is not aware of more recent data warranting reconsideration of these conclusions. General advice on setting air quality standards for carcinogenic air pollutants was given by the COC. Although the prudent assumption of the absence of any safe level for genotoxic carcinogens was preferred, a pragmatic approach based essentially on assessment of the exposure at which no increased risk would be detected, plus a safety factor, was considered reasonable for compounds like butadiene where exposure cannot be totally avoided. This approach, plus recognition that it is unadvisable to allow ambient levels of genotoxic carcinogens to rise, is used in the UK. The procedure by which the Department of Environment's Expert Panel on Air Quality Standards recommended a value of 1 ppb for butadiene based on these principles is described.

A pragmatic possible approach to the prioritization of chemical carcinogens occurring as food contaminants is described, based on the carcinogenic risk to the population. This should be of value in ensuring that resources for assessment and management of carcinogens in food are directed to the most important areas with regard to carcinogenic risk to the population. Key components of this approach are an assessment of the carcinogenic hazard to humans combined with estimations of intakes per person and of the proportion of the population exposed. These are used to derive an index referred to as the Population Carcinogenic Index. Concerning the hazard assessment expert judgement is used to place the chemical in one of five categories. The highest category is for chemical carcinogens that are believed to act by a genotoxic mechanism. It is recognised that such compounds may vary enormously with respect to their potency and various approaches to ranking carcinogens on the basis of potency are reviewed. The approach adopted is to subdivide the genotoxic carcinogens category into high, medium and low potency based on the TD50 value. Methods of estimating intakes and exposed populations are considered and an approach which groups these into broad categories is developed. The hazard and exposure assessments are then combined to derive the Population Carcinogenicity Index.

Objective: To examine the intermodal agreement of Functional Independence Measure (FIM) ratings when obtained by two commonly used approaches: telephone interview and in-person assessment of functional performance., Design: A random sample of 40 persons with hemiparesis was tested by two registered nurses trained in FIM definitions and telephone interview techniques. The two assessments occurred within 5 days of each other. The raters were blind to previous assessments. The administration of assessments was alternated to minimize bias and order effects., Setting: All subjects were assessed at home, between 3 and 10 months after discharge from rehabilitation., Patients: The criteria for inclusion were: (1) diagnosis of cerebral vascular accident (CVA); (2) completion of a minimum of 2 weeks in an acute rehabilitation program; (3) currently living at home; (4) living within a 30-mile radius of the hospital; and (5) cognitive and verbal skills adequate to complete a telephone interview. From a population of 103 patients, 40 subjects were randomly selected, 18 women and 22 men ranging in age from 37 to 90 years., Main Outcome Measures: The intermodal agreement between FIM ratings obtained by telephone interview and in-person assessment was examined using the intraclass correlation (ICC). FIM item scores were analyzed for agreement using the Kappa coefficient. The stability of the responses was determined by computing the coefficient of variation and plotting the data to visually examine the relationship between the two methods of administration., Results: Data analysis revealed that there was no statistically significant difference (p > .05) between the two methods of administration for total FIM score. The total FIM ICC was .97. ICC values for FIM subscales ranged from .85 to .98, except for social cognition. Kappa scores for noncognitive items ranged from .49 (bowel movement) to .93 (grooming). The coefficient of variation computed to examine cognitive and communication items with reduced variability indicated good stability across all items., Conclusion: The results indicated good intermodal agreement for follow-up telephone assessment using the Functional Independence Measure. The findings were limited to persons with effective communication skills.

Twenty-five affectively bipolar males were found to possess an enhanced ability to encode nonverbal cues when compared to matched controls. This ability was present during both manic and euthymic phases.

In an international study involving 33 laboratories in 11 countries, the acute oral toxicity to the rat of 20 substances and preparations was evaluated using a fixed-dose procedure and the results compared with those obtained for the test materials using the classical LD50 test. The study has shown that the fixed-dose approach to acute oral toxicity testing: (1) produces consistent results that are not substantially affected by inter-laboratory variations; (2) provides adequate information for risk assessment purposes on signs of toxicity, including their nature, time to onset, duration and outcome; (3) uses fewer animals than the current internationally agreed OECD procedure (Guideline 401-revised); (4) subjects animals to less pain and distress than the classical LD50 test and causes less compound-related mortality; and (5) enables substances and preparations to be ranked according to the EEC classification system on the basis of their acute oral toxicity, such ranking being compatible with that allocated by the results of classical LD50 studies.

National regulatory authorities have responsibility for taking decisions that possibly affect the health of whole populations and it is therefore to be expected that they will be reluctant to substitute alternative in vitro toxicity test methods for conventional animal studies unless the new procedures have been demonstrated to be reliable and have been adequately validated. Validation of in vitro methods presents particularly difficult problems because whilst they tend to produce consistent and objective results, the test systems used are incapable of mirroring the complexity of the biochemical processes seen in animals. As a result, a single animal study would need a large battery of in vitro studies to replace it to cover the various endpoints that are involved in the in vivo study; each of these in vitro tests would need to be validated with regard to the specific endpoint that it is investigating. Although great advances have been made in recent years in the development of alternative methods, few have been validated to an extent that makes them acceptable to regulatory authorities as replacements for in vivo studies. Rather, they are largely seen and used as screening techniques whereby decisions can be taken on the value of further development of newly discovered compounds, and as aids in the interpretation of animal studies and in their extrapolation to man, that is, they are of value in 'mechanism of action' studies. Nevertheless, certain in vitro procedures are already accepted by regulatory authorities and their use, for example, in 'screening out' compounds that have severe irritant properties, and in identifying compounds with potential mutagenic and carcinogenic activity, has had a profound effect on both the number of animal studies carried out and on the welfare of those animals still used.

In a multicenter study of 36 patients treated with ciprofloxacin (mean daily dosage, 986 mg per day; mean duration of treatment, 10.8 days) for a variety of infections, 32 were microbiologically proven. Of these, bacteriologic cure and/or improvement resulted in 100% of cases. For all 36 infections clinical cure and/or improvement resulted in 97.1% of cases. A total of 13 infections were classified as chronic. Overall there were six adverse reactions reported in 4/36 (11.1%) patients. Five were considered related definitely to ciprofloxacin therapy, one was not. Therapy with ciprofloxacin was discontinued in two patients (5.5%). Two patients elected to continue ciprofloxacin therapy despite mild side effects.