Tiered approach

A proper assessment of the ability of chemicals, or mixtures of chemicals, to act as endocrine disrupters requires a multi-tiered approach which is able to identify mechanisms, give early warning of adverse effects and identify which of these effects is likely to be ecologically relevant. A strategy has been proposed by Depledge and Billinghurst " and is outlined below. 

Hazardous waste burning incinerators, cement kilns, and LWAKs do not follow a tiered approach to regulate the release of toxic metals into the atmosphere. The MACT rule finalized numerical emission standards for three categories of metals mercury, low-volatile metals (arsenic, beryllium, and chromium), and semivolatile metals (lead and cadmium). Units must meet emission standards for the amount of metals emitted. For example, a new cement kiln must meet an emission limit of 120pg/m3 of mercury, 54pg/m3 of low-volatile metals, and 180 pg/m3 of semivolatile metals. 

The final emission standard under the BIF regulations limits the unit s output of HCI and chlorine gas (Cl j). These compounds combine with water in the air to form acid rain. They are also a known cause of human respiratory problems. The emission controls are implemented in the same way as the metal emissions, using the tiered approach. The owner/operator has a choice of three tiers with varying focal points. The Tier I and Tier II screening levels for waste feed and stack emission limits are located in Part 266, Appendices II and III.5... 

It is advisable, then, in a tiered approach to concentrate first on crops and activities (scenarios) that are considered to be relevant with respect to the expected level of exposure and to exclude those not relevant. Second, whether or not the toxicological properties of the product may lead to general restrictions on re-entry should be investigated. If both the likelihood of reentry and the hazard due to the toxicity of the compound cannot generally be neglected, a risk assessment over several steps should be carried out. The assessment may be based on surrogate data and "worst-case" assumptions at first and then refined, if necessary. One possible approach to a tiered evaluation procedure is presented in Figure 1. 

Tiered approach to evaluation of re-entry exposure and assignment of specific instructions for worker exposure... 

Because the whole idea of a tiered approach of the kind outlined above is in its initial stages, it will have to be validated and discussed further and will in all probability need to be refined afterwards. The aim here is to introduce the idea of a stepwise approach to the assessment of the risk to re-entry workers. The outlined procedure should be used to calculate the dermal re-entry exposure for real examples of rather dermally toxic compounds in order to gain experience with the recommended procedure. 

Tiered approach a conservative assessment of, particularly, the exposure can be used in the preliminary steps... 

S6 [53], This document includes sections on immunogenicity as well as a brief section on immunotoxicity evaluation. Notably, the use of a standard tier approach was rejected in favor of case-by-case screening, followed by mechanistic studies as necessary. 

Sarlo, K. and Clark, E.D., A tier approach for evaluating the respiratory allergenicity of low molecular weight chemicals, Fund. Appl. Toxicol., 18, 107, 1992. 

More recently, the National Institute of Environmental Health Sciences and the National Institute for Occupational Safety and Health convened a workshop in which experts in the field of developmental immunotoxicology developed a tiered approach for assaying the developmental immunotoxicity of chemicals.18 The recommended assays were separated into three groups (1) an initial set of screening assays, (2) assays for validation of a correlation between the assay end point and functional outcomes in humans, and (3) assays for research development.18 The initial screening assays included analysis of the primary antibody response to a T-dependent antigen, the delayed type... 

In view of these complexities, environmental studies that seek to verify proposed cause-effect relationships between contamination and response need to be carefully designed to avoid bias and misunderstanding. Most environmental assessments adopt a multi-tiered approach to testing, in which combinations of biological responses (biomarkers) are measured in tissue samples, body fluids or at the whole organism level to indicate exposure to or adverse effects of contamination.8. Auffret and colleagues60 surveyed Pacific oysters from the Atlantic coast of Brittany after the Erika oil spill between... 

Induced models are often used to the study the pathogenesis of, and therapeutic venues for relevant autoimmune diseases. Some of these models, in particular EAE and AA models, have also been proposed as means to evaluate the immunomodulatory effects of chemicals on established autoimmune diseases in the Tiered Approach of immunotoxicity testing. 

DeHeer C., et al., 1999 Guidance Document on the estimation of dermal absorption according to a tiered approach an update. TNO report V98 1237 27p, January 1999, Zesit, Netherlands. 

If animal testing is required, a full-scale Draize test may not be necessary given the background established in the beginning of the tier approach. For instance, the compound could be tested in a single sentinel animal to obtain confirmation of in vitro data. In addition, other modifications could be used, such as the administration of appropriate anesthetics to the test animals, or the use of the low-volume Draize modification (Falahee et al., 1982 Freeberg et al., 1984 Griffith, 1987). 

The front end of this tier approach is a screen, the functional observation battery (FOB) Gad (1982) or Irwin (1968) screen. This is the tool of choice for initial (and for most of the compounds covered by this volume, the only screen tests for) identification of potentially neurotoxic chemicals. The use of such screens, other behavioural test methods, or what are generally called clinical observations does, however, warrant one major caution or consideration. That is that short-term (within 24 hr of dosing or exposure) observations are insufficient on their own to differentiate between pharmacologic (reversible in the short term) and toxicological (irreversible) effects. 

Keywords Environmental site charaeterisation tiered approach detailed site characterization direct and indirect investigations maximum efficiency and best cost/benefit ratio... 

The objective of this article is to show how to apply a tiered approach, making broad use of non-invasive methods, where possible, especially for large industrial sites with complex sub-surface characteristics, maximizing efficiency in terms of time- and cost-effectiveness, and determining all factors necessary for the rapid design of containment measures and for long-term site remediation. 

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