No Effect Levels

Based on tests with laboratory animals, aniline may cause cancer. The National Cancer Institute (NCI) and the Chemical Industry Institute of Toxicology (CUT) conducted lifetime rodent feeding studies, and both studies found tumors of the spleen at high dosage (100 —300 mg/kg pet day of aniline chloride). CUT found no tumors at the 10—30 mg/kg per day feeding rates. The latter value is equivalent to a human 8-h inhalation level of 17—50 ppm aniline vapor. In a short term (10-d) inhalation toxicity test by Du Pont, a no-effect level of 17 ppm aniline vapor was found for rats. At high levels (47—87 ppm), there were blood-related effects which were largely reversible within a 13-d recovery period (70). 

Subchronic Studies. Although short-term repeated exposure studies provide valuable information about toxicity over this time span, they may not be relevant for assessment of ha2ard over a longer time period. For example, the minimum and no-effects levels determined by short-term exposure may be significantly lower if exposure to the test material is extended over several months. Also, certain toxic effects may have a latency which does not allow their expression or detection over a short-term repeated-exposure period for example, kidney dysfunction or disturbances of the blood-forming tissues may not become apparent until subchronic exposure studies are undertaken. 

Den Tonkelaar EM, Van Esch GJ. 1974. No-effect levels of organochlorine pesticides based on induction of microsomal liver enzymes in short-term toxicity experiments. Toxicology 2 371-380. 

The acceptable operator exposure level (AOEL) for each route of exposure is assigned from the no effect level (NOEL) in a specific toxicity test multiplied by a safety factor. The value for samples containing no detectable residues is assumed to be one half the limit of detection. For cyromazine, the seasonal use pattern indicates that the exposure is most comparable to the 21-day dermal exposure interval, and a value of 2000 mg/kg bw/day was taken as the dermal AOEL. The inhalation AOEL was obtained from a 28-day inhalation study with rats. As cyromazine is not a carcinogen, the safety margin used for calculation of the of the results using the EEC method... 

Lifetime no-effect level (NELl) Use safety factor of 10 2 an... 

The no-effect level from a subchronic (90-day) study is assigned an additional safety factor of 10 because of the shorter period of exposure (11). Hence... 

Tsuchiya K, Sugita M, Sakurai H. 1978. [Dose-response relationships at different exposure levels Reexamination in establishing no-effect levels.] Sangyo lgaku 20 247-253. (Japanese)... 

In rats exposed at concentrations of 30 or 50 ppm for 8 h for up to 5 d, methemoglobin levels returned to control values after overnight recovery (10 ppm was identified by the authors as a no-effect level), whereas in the groups exposed at 150 ppm for 8 h or 50 or 150 ppm for 12 h for a maximum of 4 d, methemoglobin levels increased with increasing days of exposure. Hematocrit levels, measured 1 w after the start of exposure, were reduced at concentrations of >30 ppm. Signs of aniline intoxication either did not occur or were not reported. 

As 5 Fed diets of 10-90 mg As/kg for 16 weeks No effect level at about 10 mg/kg diet. Some adaptation to dietary As observed in trout fed 90 mg/kg diet, as initial negative growth gave way to slow positive growth over time 9... 

Nodulated nonleguminous angiosperms, in nitrogen fixation, 17 298-299 Nodulizing process, 19 7-8 No-effect-level (NOEL), 18 541 Noise... 

End point/Concentration/Rationale The highest concentration causing no mortality in the rat after a 30-min exposure 30-min experimental no-effect-level for death (15 ppm) was used as a threshold for death in rats for the 30-min, 1-, 4-, and 8-h values. The highest concentration causing no mortality in the rat after a 10-min exposure (36 ppm) was utilized for the 10-min value. 

AEGL values for various levels of effect were derived using the following methods. The AEGL-1 was based on a controlled 1-h inhalation no-effect level of 8,000 ppm in humans. Because effects occurred in animal studies only at considerably higher concentrations, an intraspecies UF of 1 was applied. Because blood concentrations achieved equilibrium approximately 55 min into the exposure and circulating HFC-134a concentrations determine the level of effect, the 8,000 ppm concentration was applied across all time periods. 

The data base for HCFC-141b is extensive and contains studies with human subjects as well as several mammalian species. The study with human subjects was well conducted and addressed clinical symptoms, respiratory effects, cardiotoxicity, hematology and clinical chemistry effects, and pharmacokinetics. The study with humans established a no-effect level (AEGL-1) that may be conservative, because a lowest-observed-effect level was not attained. The AEGL-1 of 1,000 ppm is supported by the animal data, which show an absence of effects at concentrations that are higher by a factor of 10. Animal studies addressed both acute and chronic exposure durations as well as neurotoxicity, genotoxicity, carcinogenicity, and cardiac sensitiza... 

The determination of a true no-effect level (should one actually exist, which is debatable in some cases) is impossible given the statistical power associated with the group sizes typically used thus, the reported NOEL is very dependent on the selected group size. 

Data on the safety studies were submitted to international agencies like the Joint Expert Committee for Food Additives of the WHO and FAO (JECFA), and the Scientific Committee on Food (SCF) of the EC. Both committees endorsed acesulfame K as a food additive. Initial acceptance was based on an NOEL of 900mg/kg in dogs which were considered to be the most sensitive species. Therefore Acceptable Daily Intake (ADI) values of 0-9 mg/kg of body weight were allocated.8 9 Evidence that rats would be an appropriate model for risk assessment was the reason for JECFA to change the ADI to 0-15 mg/kg of body weight on the basis of a no-effect level of 1500-3000 mg/kg in rats.10 Countries allocating their own ADI values like the USA and Canada have come to the same conclusion. The SCF still retains its 0-9 mg/kg ADI.11... 

Alitame, L-a-aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alanine amide, has undergone a series of safety studies. While most of the studies did not show adverse effects and no indications for carcinogenicity were found, a dose-dependent increase in liver weights was found at levels above 100 mg/kg which was identified as the no-effect level. While JECFA has allocated an ADI of 0-1 mg/kg12 only a few countries, but neither the European Union nor the USA, have approved alitame. 

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