Saccharin leveling effect

During the discussions of a potential carcinogenicity of saccharin, contaminants, especially o-toluene sulphonamide, were blamed for the toxicological effects observed in these studies. The studies carried out on such contaminants which in former times occurred in concentrations well exceeding 1000 ppm, did, however, not reveal any such effects, and the observed effects today are believed to be saccharin-specific. In order to minimise risks for consumers, low maximum levels for these products were introduced into the specifications. 

D PP, Tam YK, Young LT, et al Dthium decreases Gs, Gi-1 and Gi-2 alpha-subunit mRNA levels in rat cortex. Eur J Pharmacol 206 165-166, 1991 Debhch I, Yirmiya R Naltrexone reverses a long term depressive effect of a toxic lithium injection on saccharin preference. Physiol Behav 39 547-550, 1987 DebowitzMR Social phobia. Mod Probl Pharmacopsychiatry 22 141-173, 1987 Debowitz MR, Quitkin EM, Stewart JW, et al Phenelzine vs. imipramine in atypical depression a preliminary report. Arch Gen Psychiatry 41 669-677, 1984 liebowitz MR, Quitkin EM, Stewart JW, et al Antidepressant specificity in atypical depression. Arch Gen Psychiatry 45 129-137, 1988 Liebowitz MR, Schneier F, Campeas R, et al Phenelzine vs atenolol in social phobia. Arch Gen Psychiatry 49 290-300, 1992... 

Risk assessment is a scientific process whereby the level and nature of the risk is determined. If there is no exposure to a particular chemical then there will be no risk at all, for example potassium cyanide in a sealed container is a hazard but not a risk. Risk can therefore be minimized if exposure is minimized. If the chemical is effectively non-hazardous, that is the amount needed to cause harm is unrealistically high, such as with common salt or saccharin, then even if there is a level of exposure, the risk will be so small as to be virtually non-existent. Therefore both the level of exposure and the nature of the chemical (whether or not it is hazardous) must be known if the risk is to be assessed. 

In the most recent study at the time adverse effects were detected in animals at a dietary level of 3 per cent and above, and so a NOAEL was set at a level of i per cent in the diet. This is equivalent to 500 mg of saccharin per kg of body weight, which in turn is equivalent to a person drinking about 200 cans of diet cola a day The acceptable daily intake (ADI) is determined by dividing the NOAEL by a safety factor. The safety factor used is usually 100. 

By extrapolation from the dose-response information in rats, it has been estimated that a o.oi per cent dietary level of saccharin, equivalent to about two cans of diet cola a day would lead to a lifetime risk of bladder tumours of 2.5 X 0.0000000001 (2.5 X io °) or 2.5 in ten thousand million This does not take into account the fact that (i) the bladder tumours occurred only in male rats treated in a particular way (2) the doses given were unrealistically high and (3) there is no human evidence for the effect. Thus even this estimate is erring very much on the side of caution. 

The typical level used in foods is 1-5 ppm although much higher levels may be used in certain applications such as chewing gum. Synergistic effects occur with other intense and bulk sweeteners such as acesulfame K, aspartame, polyols, and saccharin. ... 

The European Commission Scientific Committee for Food in 1997 established 1% sodium saccharin in the diet as a clear no-observed-effect level (NOEL) in relation to male rat bladder tumors and for other non-neoplastic effects of saccharin. In response to primarily updated experimental data and the extensive epidemiological data with no evidence of any relationship between saccharin intake and bladder cancer in humans, the Committee set a full acceptable daily intake (ADI) for sodium saccharin of 0-5 mg kg body weight. If the ADIs were expressed in terms of the free acid, since sodium saccharin is not the only salt used, and taking into account of the molecular weight difference between sodium saccharin (molecular weight 241) and the free acid (molecular weight 183), then ADI expressed as the free acid is 0-3.8 mg kg body weight. 

The behavioral effects of dermal exposure to maneb were studied in adult male Swiss mice (Mitchell et al. 1989). Five mice per dose group were dermally exposed to either 16, 160, or 1,600 mg/kg maneb in a conditioned taste aversion assay. Aversion to a saccharin solution was tested 24 hours following the dermal application of the compound to a shaved area on the mouse s back, immediately caudal to the skull. Maneb application did not affect taste aversion compared to water controls. Activity was measured for both ambulatory and nonambulatory activity ambulatory was when a subject sequentially disrupted at least two adjacent infrared beams in an activity monitor nonambulatory activity was when a subject sequentially broke the same beam. When given at a dose of 1,600 mg/kg, maneb increased the activity levels of a tested group (5 subjects) by 3-fold over controls. When the mice were tested individually, however, there were no... 

Aspartame and saccharin were quantitated in dietary formulations by separation on a Ci8 column (A = 210nm for aspartame and 270nm for saccharin). Separation from other matrix interferents (e.g., acesulfame, 4-sulfamoylbenzoic acid, resorcinol (internal standard), p- and o-toluenesulfonamide) was done using a 5/5/90 THF/methanol/water (80 mM triethylamine phosphate buffer at pH 3.0) in <20 min [847]. Excellent resolution and peaks shaped were observed. Standards were in the 5-lOOp.g/mL range. It should be remembered that both methanol and THF have significant absorbance at 210 nm but are used effectively in this case because they are present at very low levels. 

---