No observed adverse effects concentration

Based on no-observable-adverse effect concentration of 1.0 ng/kg BW daily in a three-generation rat study and an uncertainty factor of 100. 

Because of the first of these uncertainties (the extrapolation across species), assessments of risks to human health apply an uncertainty or safety factor of 100 to the experimentally derived no observed adverse effect concentration (NOAEC), in other words the NOAEC is divided by 100 to derive a no-effect level for human toxicity. This factor has been used since 1961, when it was chosen on an essentially arbitrary basis (RCEP, 2003, p22). In the assessment of risks to the environment, application factors of 10, 50, 100 or 1000 are applied to the results of tests carried out on specific species,2 depending on the species used and whether the tests were long term or short term. Evidence to the Royal Commission on Environmental Pollution (RCEP) for their report Chemicals in products indicated that these are merely extrapolation factors — they express the statistical variability of test results but do not effectively take into account inter-species variability, the vulnerability of threatened species, lifetime exposures or the complexity of biological systems... 

Accurate prediction of mixtures of chemicals is one of the future challenges for risk assessment and (Q)SAR modeling. Most compounds are present in the environment at concentrations far below their individual median effective concentration (EC50 or LC50) and possibly below their no-observed-adverse-effect concentrations as well, yet they may contribute to substantial effects through combination with other chemicals. It is theoretically possible to construct a (Q)SAR model to predict mixture effects however, it is generally difficult to validate their predictive power, due to a lack of experimental calibration (Altenburger et al. 2003). Semiempirical... 

NOAEC/L No-observed-adverse-effect concentration/level. The highest level of exposure to a chemical in a test that does not cause statistically significant differences from the controls in any measured negative response. 

NOAEC — No observed adverse effects concentration determined by statistical hypothesis testing methods. The effect is usually chosen for its impact upon the species tested. 

Determine the no-adverse effect concentration/no-adverse effect levels (NOAECs/NOAELs) for the endpoint(s) of concern as established in Step 4. The most appropriate NOAEC/NOAEL is used to determine the microbiological ADI. NOAEC refers to no-observable adverse effect concentration and NOAEL to a no-observable adverse effect level. 

No observed adverse effect at this concentration in H2O 72 h static test (33) unless otherwise noted. 

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).

Bd Wt = body weight F = female hr = hour(s) LCso = lethal concentration, 50% kill LOAEL = lowest-observed-adverse-effect-level M = male Musc/ske = musculoskeletal NOAEL = no-observed-adverse-effect level Resp = respiratory... 

Gd gestational day (Gl) = gastric intubation (GO) = gavage in oil Hemato - hematological incr. = increased IPTPP = isopropyl triphenyl phosphate LD = lethal dose, 50% kill LOAEL = lowest-observed-adverse-effect level M = male MCV = mean corpuscular volume MCHC = mean corpuscular hemoglobin concentration mo = month(s) Musc/skel = musculoskeletal NOAEL = no-observed-adverse-effect level NS = not specified NTE = neurotoxic esterase RBC red blood cell Resp = respiratory TBEP = tributoxyethyl phosphate TBP = tributyl phosphate TMP = trimethyl phosphate TNBP = tri-n-butyl phosphate TOP = trioctyl phosphate wk = week(s) x = times yr = year(s). 

Oberst et al. (1956) exposed nine male Wistar rats to aniline at 5 ppm for 6 h/d, 5 d/ w for up to 26 w. Exposed rats developed a mild hemoglobinemia (0.6%) with some blueness of the skin during w 23 of exposure. Based on the slight increase of methemoglobin content and the absence of spleen toxicity, U.S. EPA (1994) considered this concentration a free-standing no-observed-adverse-effect level (NOAEL). 

Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. The inhalation reference concentration is for continuous inhalation exposures and is appropriately expressed in units of mg/m3 or ppm. The RfC is operationally derived from the No-Observed-Adverse-Effect Level (NOAEL- from animal and human studies) by a consistent application of uncertainty factors that reflect various types of data used to estimate RfCs and an additional modifying factor, which is based on a professional judgment of the entire database on the chemical. The RfCs are not applicable to nonthreshold effects such as cancer. 

Bd Wt = body weight Cardio = cardiovascular d = day(s) DC so = concentration that resulted in 50% decrease in average respiratory rate EEG = electroencephalogram Endocr = endocrine F = female Gastro = gastrointestinal HCN = hydrogen cyanide Hemato = hematological LCso = lethal concentration, 50% kill LOAEL = lowest-observed-adverse-effect level M = male min = minutes NaCN = sodium cyanide NOAEL = no-observed-adverse-effect level NS = not specified (occup) = occupational Resp = respiratory sec = second(s) yr = year(s) x time(s)... 

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