Disease relevance of No-Observed-Adverse-Effect Level

• Liver sphingolipid effects and toxicity are correlated, and ceramide synthase inhibition occurs in liver and kidney at doses below their respective no-observed-effect levels [1].
• From this study it appeared that the 'no-observed-adverse-effect level' of formaldehyde was 15 and 21 mg/kg body weight/day for male and female rats, respectively [2].
• Atrophy of olfactory epithelium and hyperplasia of nasal respiratory epithelium was seen in rats exposed by inhalation to 5 ppm NVP for 7 wk but not in response to 1 ppm for 13 wk (no observed-adverse-effect level, NOAEL) [3].
• Inhaled n-butylamine produced concentration-dependent nasal epithelial hyperplasia and squamous metaplasia, inflammation and necrosis; the maternal NOAEL was less than 17 ppm [4].
• Therefore, TBZ was not teratogenic or selectively foetotoxic in mice, with no-observed-effect levels (NOEL) of 25 and greater than 200 mg/kg/day for maternal and fetal weight effects and teratogenicity, respectively [5].

High impact information on No-Observed-Adverse-Effect Level

• It is suggested that the BMD method is used as a first choice and that in cases where it is not possible to fit a model to the data the traditional NOAEL approach should be used instead [6].
• When available, cholinergic effects or brain AChE inhibition data should take precedence over RBC AChE for determining no-observed-effect levels (NOELs) [7].
• In rat forestomach, an apparent no observed effect level for ad libitum fed rats was found at 0.5% BHA (LI) and at 0.75% BHA (potential doubling time) [8].
• Six-week-old CD-1 mice were treated with 0 (solvent as control), 8 mg/kg (a dose previously established in mice as the maternal no-observed-adverse-effect level), and 16 mg/kg doses of sodium arsenite every 2 days for a total of seven i.p. injections ver a period of 14 days [9].
• The 95th percentile of vitamin A intake from foods and supplements for nonpregnant, nonlactating women aged 19-30 y also exceeds the UL but is below the NOAEL for women of reproductive age [10].

Chemical compound and disease context of No-Observed-Adverse-Effect Level

• The no-observed-adverse-effect level (NOAEL) for maternal toxicity in both species across the family of 2,4-D salts and esters was approximately 10 mg/kg/day [11].
• The results indicate that the no-observed-adverse-effect level for caprolactam is 70 mg/m3, based on upper respiratory effects, with 243 mg/m3 representing a no-observed-effect level for systemic toxicity, neurotoxicity, and lower respiratory tract effects [12].
• From the data presented in this paper the no-observed-adverse-effect level for embryo-foetotoxicity could be set at 0.5 g beta-myrcene/kg body weight [13].
• The no observed-effect-level was judged to be 50 ppm in the diet or 3.7 mg/kg body weight/day for DEHP, and 500 ppm or 36.8 mg/kg body weight/day for DNOP [14].
• The no-observed-adverse-effect level was 2000 ppm (180 mg/kg body weight/day) for tyramine, cadaverine and putrescine, 1000 ppm (83 mg/kg body weight/day) for spermidine and 200 ppm (19 mg/kg body weight/day) for spermine [15].

Biological context of No-Observed-Adverse-Effect Level

• To set occupational exposure limits (OELs) for aerosol particles, dusts, or chemicals, one has to evaluate whether mechanistic considerations permit identification of a no observed effect level (NOEL) [16].
• A no-observed effect level (NOEL) for DEA-induced changes in choline homeostasis was 10 mg/kg/day [17].
• The no-observed-effect level (NOEL) for repeated inhalation exposure to diglyme in female rats is 370 ppm [18].
• Data are sufficient to estimate an overall uncertainty factor of 3-fold with this NOAEL based on expected differences in toxicokinetics and toxicodynamics between children, and pregnant women and their fetuses, the second identified sensitive subgroup for perchlorate, and concerns about the over-iodination of this population [19].
• Reproductive and developmental toxicity in F1 Sprague-Dawley male rats exposed to di-n-butyl phthalate in utero and during lactation and determination of its NOAEL [20].

Anatomical context of No-Observed-Adverse-Effect Level

• Based on the marked increase in urinary ascorbic acid and albumin in the high dose males and the decreased forelimb grip strength in the high dose females, we concluded that the no-observed adverse effect level (NOAEL) of methanol/gasoline vapour is 500/30 ppm [21].
• A no-observed-effect level (NOEL) of 0.1 mg/kg/day was reported for inhibition of red blood cell (RBC) acetylcholinesterase (AChE) in two groups of Beagle dogs fed chlorpyrifos (0, 0.01, 0.03, 0.1, 1 or 3 mg/kg/day) in the diet for 1 or 2 years (McCollister et al., Food Cosmet. Toxicol. 12 (1974) 45-61) [22].
• It is shown here that at several times, 2% BHA stimulated the [methyl-3H]thymidine labelling index of the transitional epithelium of the urinary bladder and that at 3 months the no observed effect level was greater than 0.5% BHA [23].
• The no observed adverse effect level (NOAEL) of genistein is considered to be 50 mg/kg/day based on the presence of mild hepatic effects at the high dose of 500 mg/kg/day [24].
• The absence of evidence of an effect on thyroid function or blood cells from occupational airborne perchlorate exposure at a mean absorption of 34 mg/day demonstrates a no-observed-adverse-effect-level (NOAEL) that can assist in the evaluation of human health risks from environmental perchlorate contamination [25].

Associations of No-Observed-Adverse-Effect Level with chemical compounds

• From these results, a subchronic NOAEL of 1 mg/m(3) respirable HSCb (Printex 90) can be assigned to female rats, mice, and hamsters [26].
• For styrene, Pb, and Mn the BMD provides an objective and statistically determined threshold, which seems to be in good agreement with the estimated no-observed-adverse-effect-level (NOAEL) [27].
• Based on the results of delayed pubertal onset, the no observed adverse effect level for female reproductive development may be set at 5 mg DEHP/kg bw/day [28].
• Based on a prospective human study of EG-poisoned patients, the NOAEL for glycolate was found to be 10.1 mM [29].
• The no-observed-effect-level (NOEL) was 200 ppm, based on increased amplitude of the longer latency potentials of the FEP at 800 ppm [30].

Gene context of No-Observed-Adverse-Effect Level

• The no-observable-adverse-effect level (NOAEL) of OPG was 15 mg/kg [31].
• The above data suggests the NOAEL of bFGF in Beagle dogs is >480 mg/kg/d [32].
• A 1-mo toxicity study followed by a 1-mo recovery period of recombinant human basic fibroblast growth factor (bFGF) was performed using Beagle dogs at doses of 30, 120 or 480 mg/kg/d to estimate the no observed adverse effect level (NOAEL) [32].
• Based on animal data, regulatory strategy generally has been to postulate a no-observed-effect level (NOEL) for toxic effects and to divide this by a safety factor, usually 100, to establish acceptable levels for humans [33].
• The no-adverse-effect level (NOAEL) for PKD was determined to be 500 ppm [34].

Analytical, diagnostic and therapeutic context of No-Observed-Adverse-Effect Level

• Based on the results, the No Observable Adverse Effect Level (NOAEL) of BNP-166 soft corticosteroid in rat and dog after 28-day oral administration is 2 mg/kg [35].

References