PubMed Health⌕ Search

Biomedical subjects

F C Lu

Publications and source records attributed to F C Lu.

18 recordsLinked to original sources
PubMed1996

Safety assessment based on irrelevant toxicologic data: an extraordinary case of bromomethane used as a fumigant.

Bromomethane (BM) is a fumigant used in agriculture; it readily breaks down to bromide ion. WHO assessed the ADI of BM, at 1 mg/kg, using data on the toxicity of bromide. On the other hand, U.S. EPA used the observation of hyperplasia in the forestomach of rats given BM by gavage and arrived at a value of 0.0014 mg/kg. The validity of EPA's assessment is thus subject to question because of the data involved by (1) direct introduction of this volatile and reactive chemical to the GI by gavage and (2) using lesions in the rat forestomach which is absent in humans.

Animals↗
PubMed1995

A review of the acceptable daily intakes of pesticides assessed by WHO.

Over the past three decades, WHO has evaluated and reevaluated, through the Joint FAO/WHO Meeting on Pesticide Residues, 230 pesticides. The acceptable daily intakes (ADIs) of these pesticides are analyzed along with their scientific bases. In most cases, the evaluation process was consistent with the stated general principles and procedures of JMPR. However, the safety factors used in allocating the ADIs of several pesticides seem to be inconsistent with the severity of the toxicity, and thus, may require further consideration. These chemicals are abamectin, dinocap, procymidone, chlormequat, ethion, glyphosate, fentin hydroxide, and fentin compounds. In addition, pesticides that were evaluated many years ago, e.g., bromomethane, might merit a reevaluation in light of any relevant recent data.

Animals↗
PubMed1995

Safety/risk assessment of chemicals compared for different expert groups.

Two sets of 65 risk/safety assessments are compared. These assessments, mostly for pesticide chemicals, were developed by the World Health Organization (WHO) and the U.S. Environmental Protection Agency (EPA) at different times, often with different toxicity data, and with slightly different methods. Despite these differences, 38 sets of assessments give values that are within a 3-fold range of each other, 18 of these 38 are essentially identical (when rounded to one digit of precision), although not always for the same reasons. An additional 20 sets give values that lie within a 30-fold range; 6 sets lie within a 300-fold range; and the bromomethane ADI and RfD are 700-fold apart. In addition, on average the EPA values are lower than the WHO numbers. These comparisons are discussed in relationship to a developing world-wide consensus that the methods for evaluating the safety/risks from various chemicals should be more consistent and the resulting assessments should be more comparable. Moreover, we argue that an established assessment and associated information from one expert group should be routinely discussed in the ongoing evaluation of a chemical by another expert group. A procedure for effecting more consistency among such expert groups is proposed.

Environmental Health↗
PubMed1992

Safety/risk assessment of pesticides: principles, procedures and examples.

The principles and procedures for the assessment of the safety/risk of chemical used by the relevant WHO and EPA expert groups are outlined. The assessment in terms of acceptable daily intakes (ADIs) and reference doses (RfDs) of 25 pesticides is listed. The pesticides assessed are acephate, alachlor, amitrole, azinphos-methyl, benomyl, biphenthrin, bromophos, chlordane, chlorthalonil, cyhalothrin, DDT, EPTC, ethion, folpet, fosetyl-al, glyphosate, isofenphos, methomyl, methyl mercury, paraquat, phosphamidon, systhane, terbutyn, tribultyltin oxide, and vinclozin. In addition, their critical effects, the no-observed-effect levels and the size of the safety/uncertainty factors used are also listed to illustrate the diversity of the toxic effects and the resulting assessments. Furthermore, the enormous amount of data reviewed and the complex scientific judgement involved are also indicated. Considering the various uncertainties existing, the ADIs and RfDs do not differ appreciably in most instances. However, marked differences exist between the ADIs and RfDs of DDT and chlordane. It is suggested that re-evaluation be done on these, and perhaps other, chemicals.

Animals↗
PubMed1991

Assessment of safety/risk of chemicals: inception and evolution of the ADI and dose-response modeling procedures.

This article reviews the procedures for the assessment of safety/risk of chemicals to human health. Because the nature and severity of toxicity and the extent of the database vary from chemical to chemical, the assessment is done on a case by case basis. Essentially 5 steps are involved in the assessment: (a) identification of hazards based on appropriate human and animal data; (b) determination of the dose-response relationship of the adverse effects of the chemical; (c) extrapolation of the dose-response data from test subjects to human populations; (d) estimation of the exposure; and (e) assessment of the safety/risk of the chemical under a specified exposure. Emphasis in this article, however, is placed on the extrapolation of the dose-response data to the human situation. The extrapolation is done by the identification of a no-observed-adverse-effect level (NOAEL) and the application of a safety factor, thereby arriving at an acceptable daily intake (ADI). The safety factor is selected on the basis of, inter alia, the severity of the adverse effect and the adequacy of the database. On the other hand, with genotoxic carcinogens, mathematical modeling is used for extrapolation. This is because the effects of genotoxic carcinogens are generally believed to have no threshold. The ADI approach, which involves the identification of a NOAEL, is therefore not applicable. A number of mathematical models have been developed to assess, from the dose-response data, either the risks that may be associated with a specified dose, or the 'virtually safe dose' at a specified risk level. The evolution, application and shortcomings of these procedures and the potential improvements in the ADI approach and in the dose-response characterization based on these mathematical models are also discussed.

Animals↗
PubMed1989

Hobson's choice.

Explore the source record for details and available documents.

Animals↗
PubMed1988

Acceptable daily intake: inception, evolution, and application.

The acceptable daily intake (ADI) approach to toxicological evaluation was initiated by the Joint FAO/WHO Expert Committee on Food Additives in 1961. The procedure involves collecting all relevant data, ascertaining the completeness of the available data, determining the no-effect level using the most sensitive indicator of the toxicity, and applying an appropriate safety factor to arrive at the ADI for man. This procedure was also adopted by the Joint FAO/WHO Meeting of Experts on Pesticide Residues later in 1961. In the ensuing years, hundreds of food additives and pesticide residues have been evaluated and reevaluated by these two international expert groups. The ADIs, used nationally and internationally in the elaboration of food standards, have proved satisfactory in permitting the judicious use of these chemicals and in protecting the health of the consumer. The success of this endeavor over the years can be attributed to the dedication and hard work of the many international experts involved as well as to the cooperation of the chemical industry in submitting all relevant published and unpublished data. It is envisaged that this approach will continue to be followed in evaluating and reevaluating additives, pesticides, and contaminants, and that it will likely be extended to other situations where toxicological evaluation forms the scientific basis of control measures.

Animals↗
PubMed1985

Safety assessments of chemicals with thresholded effects.

Toxicological evaluation of chemicals with thresholded effects involves the estimation of their acceptable daily intakes (ADI). The following steps are involved in the evaluation: judging the completeness of the available chemical and biological data, determination of the no-effect level (NEL), selection of an appropriate safety factor, and extrapolation of the NEL to the ADI using the selected safety factor. The relative insignificance of the sample size on the NEL, the advantages of body weight (compared to the body surface) as a basis for interspecies extrapolation, the size of the safety factor as a function of the nature of the toxic effects, and the multiplicity of the toxicological investigations, in addition to the conventional short-term and long-term toxicity studies, are described. In addition, the possible inadvisability of overemphasizing the importance of dose-response relationship at the expense of in-depth, relevant studies is discussed.

Animals↗
PubMed1983

Toxicological evaluations of carcinogens and noncarcinogens: pros and cons of different approaches.

Toxicological evaluations are performed to provide estimates of the safety/risk entailed in specified exposures to chemicals. This paper presents the two common approaches to toxicological evaluations. One of these assumes the presence of threshold doses. It involves determination of no-effect levels and extrapolation to acceptable daily intakes in man. This procedure has been widely and successfully used for noncarcinogens. For carcinogens, a number of mathematical models have been proposed for estimating the level of risk associated with a specified exposure level or the dose that is considered virtually safe, e.g., with a risk level of 10(-6). Variations of these major approaches are also outlined. Examples are included to indicate that a deficiency of significant biological data, such as an unexpected toxic effect and the marked influence of modifying factors, can invalidate a toxicological evaluation. It is also pointed out that such deficiencies cannot be overcome by any mathematical manipulation of the available dose-response data.

Animals↗