Persistent organic pollutants: potential health effects?

It is not a point of debate that the Stockholm Convention for the prevention of further accumulation of persistent organic pollutants (POPs) should be ratified and implemented by all countries. However, in their article, Schafer and Kegley present an unbalanced "worst case scenario". Approximately 20% of the food supply of the US is contaminated with POPs at extremely low levels; these levels are comparable to those found in many other countries. Furthermore, there is no scientific consensus that these levels are hazardous to most humans. More information is needed to determine the actual risks of extremely low levels of POPs to human health.

Acute intake assessment: evolution within the Codex Committee on Pesticide Residues. WHO Joint Secretary of the Joint FAO/WHO meeting on pesticide residues JMPR.

The Codex Committee on Pesticide Residues (CCPR), in its development of international standards, has been considering during the last few years the implications of residues of acutely toxic pesticides in food commodities. CCPR has asked its scientific advisory body, the Joint FAO/WHO Meeting on Pesticide Residues (JMPR), for advice on the safety of the standards that are being developed. This work began in 1993. The 1994 JMPR first decided to use the 'acute reference dose' as a toxicological benchmark for a 'short-term ADI'. A number of acute reference doses have been allocated at subsequent meetings. The 1998 JMPR decided to consider the allocation of an acute reference dose whenever a full evaluation of a pesticide is undertaken. General guidance for the allocation of an acute reference dose was provided by the 1998 JMPR, which is discussed in this paper.

Background to the ADI/TDI/PTWI.

International scientific committees such as the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and the Joint FAO/WHO Meeting on Pesticide Residues (JMPR), regional scientific committees such as those of the European Union, and national regulatory agencies generally use the safety factor approach for establishing acceptable or tolerable intakes of substances that exhibit thresholds of toxicity. The acceptable daily intake (ADI) is used widely to describe "safe" levels of intake; other terms that are used are the reference dose (RfD) and tolerable intakes that are expressed on either a daily (TDI or tolerable daily intake) or weekly basis. JECFA uses the term PTWI, or provisional tolerable daily intake, for contaminants that may accumulate in the body. The weekly designation is used to stress the importance of limiting intake over a period of time for such substances. When using this approach no-observed-effect levels (NOELs) or no-observed-adverse-effect levels (NOAELs) are identified in the critical studies, to which appropriate safety or uncertainty factors are applied. Although the value of safety factors varies depending upon a number of factors, 100 is most often used, which is designed to account for interspecies and intraspecies variations. Within the framework of the IPCS project on harmonization of approaches to the assessment of risk from exposure to chemicals, issues relating to uncertainty and variability are being addressed with the aim of relying, whenever appropriate, on data-derived safety/uncertainty factors. The ILSI Europe ADI Task Force has, for the past few years, been considering the scientific basis for the safety factor, which will be discussed by other speakers in the workshop. The value of the NOAEL is dependent on the design of the study. Because of the expense and time required conduct many studies, doses are usually spread over wide intervals. Thus, the no-observed-adverse-effect level may be considerably less than a marginally effective dose. In addition, use traditionally has not been made of the dose-response relationship when establishing ADIs. Newer approaches such as the benchmark dose may provide ways of making use of dose-response information. It is unlikely that consumption at the level of the ADI will result in significant risk to the consumer because of the conservatisms that are built into it. It usually is based on long-term studies that are intended to mimic consumption over the lifetime of humans. The ADI is applied to "discretionary" chemicals (food additives, veterinary drugs, and pesticides) by JECFA and JMPR, which are relatively easy to control if safety problems are identified. On the other hand, when tolerable intakes are derived for contaminants that are present in the environment at high levels, the use of standard safety factors could result in discarding large portions of the food supply. Thus, it is very important that the basis for the tolerable intake is fully described so that informed judgments can be made about the health consequences of exceeding it.

Drug-resistant tuberculosis: mechanisms and management.

Infection with Mycobacterium tuberculosis remains a major global health problem and the recent outbreaks of multidrug resistant (MDR) tuberculosis have been a major cause for concern. An accurate picture of the extent of this problem is not possible because only a limited number of countries have reliable surveillance programmes. However, the experience in the USA reinforces the need for strict adherence to standard public health measures and good clinical practices to minimise the impact of MDR tuberculosis in the human immunodeficiency virus era.

Bactericidal in-vitro activity of beta-lactams and beta-lactamase inhibitors, alone or associated, against clinical strains of Acinetobacter baumannii: effect of combination with aminoglycosides.

Five Acinetobacter baumannii strains of various phenotypes were selected on the basis of the results of a national survey in France in 1991. beta-Lactamases in Acinetobacter isolates were characterized by isoelectrofocusing. We carried out a 24 h time-kill study to assess the bactericidal effect of antibiotic alone or in combination against A. baumannii strains. The initial inoculum was 10(6) cfu/mL. Antibiotics were tested at MIC x 2 when an antibiotic was tested alone and at the MIC for each combination including ticarcillin, piperacillin, ceftazidime or imipenem with or without amikacin or netilmicin and/or beta-lactamase inhibitors. Concentration of inhibitors were: 2 mg/L for clavulanic acid, 4 mg/L for tazobactam and 8 mg/L for sulbactam. Sulbactam and tazobactam showed an intrinsic in-vitro activity against strains susceptible to ticarcillin. A complete killing at 24 h was observed when beta-lactams were combined with amikacin in comparison with antibiotics alone. Synergy was lost when the strain presented a low resistance level to beta-lactams or aminoglycosides except for ticarcillin. Combinations of sulbactam with ticarcillin showed the best bactericidal activity against strains multiresistant to beta-lactams.

The role of the World Health Organization in the evaluation of pesticides.

The International Programme on Chemical Safety (IPCS), which is a cooperative program of the World Health Organization (WHO), United Nations Environment Programme (UNEP), and International Labour Organisation (ILO), directs a number of pesticide activities, including the WHO component of the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) and the preparation of Environmental Health Criteria (EHC) documents and Health and Safety Guides (HSGs) on pesticides. The intake of pesticide residues is being predicted at the international level, which is based upon the maximum residue limits (MRLs) that are estimated by JMPR. Acceptance of the MRLs is increased when the prediction does not exceed the acceptable daily intake (ADI). IPCS is active in developing new methodologies and in developing scientific consensus documents on the assessment of health risks from exposure to chemicals. Two new initiatives are a project to obtain agreement among important national institutions on the approaches to be taken for the interpretation of data relating to specific effects and the development of a "Joint Meeting on Pesticides," which will provide comprehensive reviews of pesticide safety and use.