NOAEL effect level

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-... 

Cancer Effect Level-Humans A LOAEL. More Serious-Humans A LOAEL, Less Serious-Humans A NOAEL - Humans... 

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... 

No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no statistically or biologically significant increases in frequency or severity of adverse effects seen between the exposed population and its appropriate control. Effects may be produced at this dose, but they are not considered to be adverse. 

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).

CEL A Cancer Effect Level (CEL) is the lowest exposure level associated with the onset of carcinogenesis in experimental or epidemiologic studies. CELs are always considered serious effects. The LSE tables and figures do not contain NOAELs for cancer, but the text may report doses not causing measurable cancer increases. 

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... 

NOAEL = no-observable-adverse-effect level Resp = respiratory wk = week(s). 

Cancer Effect Level-Animals LOAEL, More Serious-Animals LOAEL, Less Serious-Animals NOAEL - Animals... 

AP = alkaline phosphatase ATPase = adenosine triphosphatase Cardio = cardiovascular d = day(s) Endocr = endocrine F = female Gastro = gastrointestinal Gn pig = guinea pig GOT = glutamic-oxaloacetic transaminase GPT = glutamic-pyruvic transaminase Hemato = hematological hr = hour(s) LDH = lactate dehydrogenase LOAEL = lowest-observable-adverse-effect level M = male Musc/skel = musculoskeletal NOAEL = no-observable-adverse-effect level ... 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious effects during a lifetime. The RfD is operationally derived from the No-Observed-Adverse-Effect Level (NOAEL- from animal and human studies) by a consistent application of uncertainty factors... 

NO ALL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at which no harmful effects were seen in the organ system studied. Key number 18 reports a NOAEL of 3 ppm for the respiratory system which was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see footnote "b"). 

COL = cancer effect level d = days(s) hr = hour(s) LOAEL = lowest-observed-adverse-effect level mo = month(s) NOAEL = no-observed-adverse-effect level Resp = respiratory wk = week(s)... 

NOAEL (no-observed-adverse-effect level) is defined as the highest dose at which no adverse effects are observed in the most susceptible animal species. The NOAEL is used as a basis for setting human safety standards for acceptable daily intakes (ADIs), taking into account uncertainty factors for extrapolation from animals to humans and inter-individual variabilities of humans. The adequacy of any margin of safety or margin of exposure must consider the nature and quality of the available hazard identification and dose-response data and the reliability and relevance of the exposure estimations. In some cases, no adverse endpoint can be identified such as for many naturally occurring compounds that are widespread in foods. In that case, an ADI Not Specified is assigned. ... 

The quantitative measurement of toxicity level is expressed by parameters like NOEL (no observed effect level), NOAEL (no observed adverse effect level), and ADI (acceptable daily intake). The NOEL values are divided by 100 to obtain ADI values. The 100 safety factor derives from 10 x 10, where the 10s represent the animal-to-human conversion rate and the human variability factor. Currently, the most useful index of safety is the ADI, expressed as milligrams of test substance per kilogram of body weight (ppm), with the recommendation not to eat more than the ADI per day. The FDA, EU, and WHO agree on the ADI principle. 

To calculate the safe re-entry interval (REI), the margin of exposure (MOE) must be considered. Worker risk is measured as a margin of exposure and is related to how closely the occupational exposure comes to the no observed adverse effect level (NOAEL, for oxamyl 50 mg kg day ). MOE is defined as... 

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