Information section--Fd Chem. Toxic. Vol. 21, no. 1 115

repeated challenges following periods when the patient has been symptom free on a diet from which the suspected food has been eliminated. The com- plexity of western diet, however, often prevents identi- fication of the offending substance. The ingestion of artificial chemicals in foodstuffs may also lead to food intolerance. Adverse reactions to salicylates, cycla- mates, saccharin and tartrazine are well-documented and many aspirin-sensitive patients are intolerant of tartrazine, benzoates and the analgesics indomethacin and paracetamol (Bleumink loc. tit.; Doeglas, Br. J. Derm. 1975, 93, 135; Stenius & Lemola, Clin. Allergy 1976, 6, 119). It has been postulated that the inhi- bition of the synthesis of prostaglandins PGE2 and PGF2 by these substances may result in their effects. Since inhibitors of prostaglandin synthesis have been demonstrated to regulate suppressor-cell function (Nicklin & Shand, Int. J. lmmunopharmac, 4, 407) and inhibition of prostaglandin synthesis can thus lead to enhancement of antibody production, an immune component may be involved in these adverse reac- tions.

Conclusion In summary, it has recently been established that

food allergy may be divided into three categories. Anaphylactic reactions (Type I) are observed in atopic individuals, and overlap with inhalant hypersensiti- vity (children are particularly vulnerable to this type of reaction). Type III reactions have slightly delayed symptoms which usually occur after the consumption of milk, egg and possibly certain cereals. The Type IV reactions appear rarely to be elicited by food constitu- ents, although better methods for diagnosis of Type IV reactions are needed. Finally, whilst not discussed here, there are a number of observations linking food allergic disease with genetic predisposition. Clinical and laboratory observations led to the conclusion that the avoidance of allergens in infancy is important because of the immaturity of the mechanisms that limit allergen absorption and because of the risk of establishing patterns of response in genetically susceptible infants that will lead to persistent allergic disorders.

[K. Miller--BIBRA]

BHA carcinogenicity study

Ishiwata, H., Kaneko, K., Kato, S. & Tanimura, A. (1982). Decrease of butylated hydroxyanisole added in the diet for a carcinogenicity test in rats and mice. Bull. ent~ir. Contam. Toxicol. 28, 379.

Recently (Cited in F.C.T. 1982, 20, 971) we pub- lished an abstract of a brief paper that reported the induction of squamous-cell carcinomas of the fore- stomach in rats fed diets containing 0.5 or 2°/L butyl- ated hydroxyanisole (BHA). A subsequent paper (cited above) has made it clear that the levels of BHA that were actually present in the feed were consider- ably less than was reported.

The feed pellets used in the carcinogenicity study were produced by a commercial feed manufacturer by mixing appropriate amounts of BHA into the pow- dered basal semi-synthetic diet and then steam pellet- ing the feed and drying it in a hot air stream. Pellets were made up to contain 0.02, 0.2, 0.5, 1 or 2",L BHA. However gas chromatographic (GC) analysis of n-hexane extracts of 'pieces of' the pellets revealed that most of the pellets contained only 50% or less of the indicated concentrations of BHA. The amount of BHA present varied quite widely; five samples of each of the '0.5' and "2°,;' BHA pellets contained 0.19-0.28 and 0.79-1.291'L BHA, respectively.

Experiments were carried out to determine the likely reason for the loss of the antioxidant from the pellets. An open glass dish containing a solution of 50 mg "reagent grade' BHA in n-hexane was left at room temperature until the solvent had evaporated and was then heated at 80'C in a drying oven. Resi- dual BHA was dissolved in n-hexane and determined by UV absorption. About 15311 of the BHA remained in the dish after 2 hr heating. When 50 mg BHA was

mixed with 5 g powdered basal diet and heated at 8OC in the drying oven, GC analysis of n-hexane extracts of the diet revealed that the BHA content of the diet had decreased by about 30",; over 2hr. Further tests were carried out in sublimation bottles maintained at 80"C in a water bath for 2 hr. With BHA alone, about 55% remained in the bottle and 42% sublimed. When BHA (50 rag) was mixed with the feed (5 g) about 90°,, of the BHA was recovered from the bottle and about 6!',, sublimed. In all of the experiments the only peaks observed in GC analyses of the n-hexane extracts of the diet were for BHA. No UV absorption or GC peaks were observed in the n-hexane in the traps of the sublimation bottles, nor in the acetone used to rinse the glass dishes and subli- mation bottles after they had been rinsed with n-hex- ane. The authors assume that during the process of manufacturing the pellets, which involved ventilation as well as heating, a greater decrease in the BHA content of the diet would occur than did so in their controlled experiments. They consider that the major cause of the loss of BHA from the pellets was subli- mation during the steaming and heating processes.

[-These analyses were carried out before the carci- nogenicity study began but were not mentioned in the previous paper. No details are given in either this or the previous paper (ibid 1982.21k 971) on the purity of the BHA used or the method by which it wits added to the diet and no details of the components of the diet are presented. It hits been suggested that the steam pelleting may have resulted in a reaction product between BHA and a component of the diet (Food Chemical News 1982, 24 (17), 30} although no evidence of this is presented in this paper. Whether any loss of BHA or formation of reaction products occurred during storage cannot be assessed from this study.]