Lowest adverse effect level

LABORATORY WHITE RAT Diet No adverse effect level Lowest adverse effect level (histological damage) 4.0 mg/kg ration, equivalent to 0.29-0.38 mg toxaphene/kg body weight daily (Chu etal. 1988) 20.0 mg/kg ration (Chu etal. 1988)... 

As a consequence of the distinction between non-adverse effects and adverse effects, a tme No-Effect Level (NEL) and No-Adverse-Effect Level (NAEL) as well as a tme Lowest-Effect Level (LEL) and Lowest-Adverse-Effect Level (LAEL) exists in theory for a non-adverse effect and adverse effect, respectively. This is illustrated in Figure 4.6 where the NEL is the intersection of the dose-response curve with the x-axis, and the LEL, NAEL, and LAEL are somewhere on the dose-response curve. 

FIGURE 4.6 Dose-response curve illustrating the true no-effect level (NEL) and no-adverse-effect level (NAEL) as well as the true lowest-effect level (LEE) and lowest-adverse-effect level (LAEL). 

Lowest adverse effect level (histological damage)... 

For noncarcinogens, in which the dose response is believed to show a threshold, a dose can be determined at which there is no adverse effect, the NOAEL (Fig. 2.12). The effect will be one that is likely to occur in humans and which is the most sensitive toxic effect observed. If a NOAEL cannot be determined (if the data is insufficiently robust), then the "lowest adverse effect level (LOAEL)" is determined (Fig. 2.12). 

Figure 2.12 Dose-response curve showing the NOAEL, LOAEL, and threshold points. Abbreviations NOAEL, no observed adverse effect icojj level LOAEL, lowest adverse effect level.

In conclusion, a rough estimate of the lowest adverse effect level (LOAEL), on a molar basis, may be provided for adults - pralidoxime chloride HI 6 dichloride obidoxime dichloride trimedoxime dichloride = 2 1.3 0.4 0.25 mmol. 

Bonde, J.P., Ioffe, M., Apostoh, P., Dale, A., Kiss, P., Spano, M., et al., 2002. Sperm count and chromatin structure in men exposed to inorganic lead lowest adverse effect levels. Occup. Environ. Med. 59, 234—242. 

In risk characterization, step four, the human exposure situation is compared to the toxicity data from animal studies, and often a safety -margin approach is utilized. The safety margin is based on a knowledge of uncertainties and individual variation in sensitivity of animals and humans to the effects of chemical compounds. Usually one assumes that humans are more sensitive than experimental animals to the effects of chemicals. For this reason, a safety margin is often used. This margin contains two factors, differences in biotransformation within a species (human), usually 10, and differences in the sensitivity between species (e.g., rat vs. human), usually also 10. The safety factor which takes into consideration interindividual differences within the human population predominately indicates differences in biotransformation, but sensitivity to effects of chemicals is also taken into consideration (e.g., safety faaor of 4 for biotransformation and 2.5 for sensitivity 4 x 2.5 = 10). For example, if the lowest dose that does not cause any toxicity to rodents, rats, or mice, i.e., the no-ob-servable-adverse-effect level (NOAEL) is 100 mg/kg, this dose is divided by the safety factor of 100. The safe dose level for humans would be then 1 mg/kg. Occasionally, a NOAEL is not found, and one has to use the lowest-observable-adverse-effect level (LOAEL) in safety assessment. In this situation, often an additional un-... 

LOAEL lowest-observed-adverse-effect level... 

Cardio - cardiovascular LD = Lethal dose, 50% kill LOAEL = lowest-observable-adverse-effect level mg/kg/day = milligram per kilogram per day NOAEL = no-observable-adverse-effeot level... 

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study, or group of studies, that produces statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control. 

Tables (3-1, 3-2, and 3-3) and figures (3-1 and 3-2) are used to summarize health effects and illustrate graphically levels of exposure associated with those effects. These levels cover health effects observed at increasing dose concentrations and durations, differences in response by species, minimal risk levels (MRLs) to humans for noncancer end points, and EPA s estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and figures for a quick review of the health effects and to locate data for a specific exposure scenario. The LSE tables and figures should always be used in conjunction with the text. All entries in these tables and figures represent studies that provide reliable, quantitative estimates of No-Observed-Adverse-Effect Levels (NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels (CELs).

Levels of significant exposure for each route and duration are presented in tables and illustrated in figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies. LOAELS have been classified into "less serious" or "serious" effects. "Serious" effects are... 

Bd Wt = body weight Cardio = cardiovascular d = day(s) Endocr = endocrine F = female Gastro = gastrointestinal Hemato = hematological hr = hour(s) LC50 = lethal concentration, 50% kill LOAEL = lowest- observable-adverse-effect level M = male Musc/skel = musculoskeletal ... 

LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest dose used in the study that caused a harmful health effect. LOAELs have been classified into "Less Serious" and "Serious" effects. These distinctions help readers identify the levels of exposure at which adverse health effects first appear and the gradation of effects with increasing dose. A brief description of the specific endpoint used to quantify the adverse effect accompanies the LOAEL. The respiratory effect reported in key number 18 (hyperplasia) is a Less serious LOAEL of 10 ppm. MRLs are not derived from Serious LOAELs. 

---