Lowest observable effects levels

Summary of Lowest Observed Effect Levels for Key Lead-Induced Health Effects in Adults... 

Lowest observed effect level (PbB) (Mg/dl) Heme synthesis and hematological effects Neurological effects Renal system effects Gastrointestinal effects ... 

Lowest-Observed-Effect-Level (LOEL) In dose-response experiments, the lowest exposure level at which there are statistically or biologically significant increases in the frequency or severity of any effect between the exposed population and its appropriate control group. 

Although this study (Hart 1980) did not identify an effect level, the NOAEL in this study is below the lowest-observable-effect level (LOEL) found in all studies examining the toxicity of diisopropyl methylphosphonate. The LOEL for diisopropyl methylphosphonate is 345 mg/kg/day for male mink, and 455 mg/kg/day for female mink (average 400 mg/kg/day), doses at which statistically significant decreases in plasma (butyrylcholinesterase) but not RBC cholinesterase (acetylcholinesterase) activity was observed (Bucci et al. 1994). No effects were observed at 63 mg/kg/day in males and 82 mg/kg/day in females (average 73 mg/kg/day). A decrease in plasma cholinesterase activity is considered to be a marker of exposure rather than a marker of effect, while decreases in RBC acetylcholinesterase activity is thought to reflect decreases in brain acetylcholinesterase activity and is considered adverse. 

In the case of noncarcinogenic substances, there exists a threshold this is an exposure with a dose below which there would not be adverse effect on the population that is exposed. This is the reference dose (RfD), and it is defined as the daily exposure of a human population without appreciable effects during a lifetime. The RfD value is calculated by dividing the no observed effect level (NOEL) by uncertainty factors. When NOEL is unknown, the lowest observed effect level (LOEL) is used. NOEL and LOEL are usually obtained in animal studies. The main uncertainty factor, usually tenfold, used to calculate the RfD are the following the variations in interspecies (from animal test to human), presence of sensitive individuals (child and old people), extrapolation from subchronic to chronic, and the use of LOEL instead of NOEL. Noncancer risk is assessed through the comparison of the dose exposed calculated in the exposure assessment and the RfD. The quotient between both, called in some studies as hazard quotient, is commonly calculated (Eq. 2). According to this equation, population with quotient >1 will be at risk to develop some specific effect related to the contaminant of concern. 

The data base for HCFC-141b is extensive and contains studies with human subjects as well as several mammalian species. The study with human subjects was well conducted and addressed clinical symptoms, respiratory effects, cardiotoxicity, hematology and clinical chemistry effects, and pharmacokinetics. The study with humans established a no-effect level (AEGL-1) that may be conservative, because a lowest-observed-effect level was not attained. The AEGL-1 of 1,000 ppm is supported by the animal data, which show an absence of effects at concentrations that are higher by a factor of 10. Animal studies addressed both acute and chronic exposure durations as well as neurotoxicity, genotoxicity, carcinogenicity, and cardiac sensitiza... 

IDLH Immediately Dangerous to Life and Health. The OSHA definition for IDLH is the maximum concentration of contaminant from which one can escape in 30 minutes without suffering irreversible health effects or escape-impairing effects such as dizziness, fatigue, impaired judgement, or slowing. Based on human and animal studies IDLH may be considered the LOEL (lowest observable effect level) or 500 x PEL if no other data are available or any concentration... 

Lowest-observed-effect level (LOEL) The lowest concentration or amount of a substance, found by experiment or observation, that causes any alteration in morphology, functional capacity, growth, development or life span of the target organism distinguishable from normal (control) organisms of the same species and strain under the same defined conditions of exposure. 

Taking into account a variety of toxic end-points of chronic acrylonitrile treatment in Fischer 344 rats, Salsburg (1990) calculated a lowest observable effect level of 3 ppm (mg/L) in drinking water, while 1 ppm acrylonitrile was estimated to be a no mean effect level . 

One principle that is central to the understanding of toxicology is the dose-response relationship, which implies that there is a threshold level below which no toxic effects are observed. This level can be approximated in studies in which animals are dosed with the pesticide the maximum dose tested at which there are no detectable differences between treated and untreated control animals is called the no observed effect level (NOEL). The dosage slightly in excess of the NOEL at which toxic effects are observed is referred to as the lowest observed effect level (LOEL). These two dosages should be relatively close together in order to clearly define the threshold level. 

Lowest observed effect level (LOEL) is the lowest dose of a substance that has been observed to produce either a statistically or biologically significant increase in the frequency or severity of an effect, compared to the frequency or severity at zero dose. 

A comparison of concentrations in eggs of free-ranging birds with the lowest observed effect levels for reproduction or deformities has been presented recently.46 It was concluded that adverse effects may be expected from PCBs for herring gull, great blue heron, Forster s tern and common tern at several locations in the world. 

Subacute or subchronic assays assess the effects of daily exposures of an animal population to a toxicant over approximately 10% of the animal s lifetime. In rats, this corresponds to about 3 months. Careful study of the animals—including examination of all body tissues and fluids—reveals the dose at which toxic effects begin to occur at several endpoints, such as organ dysfunction, behavioral changes, or alterations in levels of normal body fluid components. The highest dose at which none of the animals show toxic effects is called NOAEL (i.e., no observable adverse effect). Other doses include LOEL (lowest observed effect level), the lowest dose for which effects were expressed and LOAEL (lowest observed adverse effect level), a stricter version of LOEL that addresses only adverse effects. In these tests several species are tested and the most sensitive one is selected as a human surrogate. See Figure 9.32. 

Van Helden, H.P.M., Trap, H.C., Oostdijk, J.P., Kuipers, W.C., Langenberg, J.P., Benschop, H.P. (2003). Long-term, low-level exposure of guinea pigs and marmosets to sarin vapor in air lowest-observable-effect level. Toxicol. Appl. Pharmacol. 189 170-9. 

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