No adverse observed effect levels

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. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor approach. They are below levels that might cause adverse health effects in the people most sensitive to such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level above the MRL does not mean that adverse health effects will occur. 

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... 

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

GO) = gavage in oil (GW) = gavage in water Gd = gestation day Hemato = hematological LD50 = lethal dose, 50% kill LOAEL = lowest-observable-adverse-effect level M = male Metab = metabolic 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... 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor approach. They are below levels that might cause adverse health effects in the people most sensitive to such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. 

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"). 

Flinterman AE. Pasmans SG. Hoekstra MO. Meijer Y. van Hoffen E. Knol EF. Hefle SL, Bruijnzeel-Koomen CA. Knulst AC Determination of no-observed-adverse-effect levels and eheiting doses in a representative group of peanut-sensitized children. J Allergy Clin Immunol 2006 117 448-454. 

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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