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Present and future uses of mutagenicity tests for assessment of the safety of food additives.

The tier approach has been employed for the past 3 years for investigating the potential mutagenicity of food additives and generally recognized as safe (GRAS) substances. This approach is used to set testing priorities, since a large number of substances must be investigated. Three tiers or testing levels are used. The first tier is a pre-screen to determine whether a chemical has the potential to cause genetic damage. The second tier is designed to ascertain whether mutagenic activity detected at tier one can be confirmed in the tests which are a part of tier two. The third tier is used for risk assessment and, as such, attempts to define the genetic risk to humans that is associated with use of a substance which is a confirmed mutagen as defined by one or more test methods in tier two. The future uses of mutagenicity test methods will probably be in the area of short-term tests for carcinogenicity and as a means of assessing the risk associated with the use of gentically active chemicals.

Animals↗

Use of nitrates and nitrites as food additives in Nordic countries.

An account is given of the presently permitted use of nitrates and nitrites as food additives in Denmark, Finland, Norway and Sweden. Nitrate permitted to be added to milk for the production of solid, semisolid and mould cheeses at levels of 150-200 mg/l potassium nitrate. Due to the potential formation of especially nonvolatile N-nitroso compounds, attempts are made to reduce their use. Nitrates, but not nitrites, are still permitted in certain semipreserved fish products (herring) in Denmark, Finland and Sweden, but it will probably be phased out within a few years. Nitrates are not permitted in meat products in Norway and Sweden, while the use is being reduced in Denmark and Finland. The use of nitrite (175-200 mg/kg meat product of sodium nitrite) is generally permitted as a preservative in meat products in Sweden, Finland and Denmark, while it is more restricted in Norway. Due the potential risk of formation of carcinogenic N-nitroso compounds in the meat and in the organism of the consumer serious attempts are made to reduce the use of all Nordic countries.

Animals↗

Nutritional transition during infancy in East Java, Indonesia: 1. A longitudinal study of feeding pattern, breast milk intake and the consumption of additional foods.

Infant feeding pattern was studied longitudinally from birth to 52 weeks among all infants born in the period September 1982-December 1984 in three villages in Madura, East Java (n = 687). Genuine demand breast-feeding was practised but it is the custom to force-feed infants from as early as the third day after birth until about 16 weeks. In a sub-sample the intake of breast milk and additional foods were measured, longitudinally in 76 infants and cross-sectionally in 77 infants. Breast milk intake ranged from 745 g per 24 h in the first month to 640 g per 24 h in the 12th month. Force-feeding did not have a negative influence on breast milk intake. The main constraint in infant feeding is the low intake of additional foods, which remained at 180 kcal and 3 g protein per day from the age of 16 weeks onwards.

Breast Feeding↗

The approach taken and conclusions reached by the Joint FAO-WHO Expert Committee on Food Additives.

The synthetic anabolic steroid trenbolone acetate (TBA) was evaluated by the Joint FAO-WHO Expert Committee on Food Additives (JECFA) in 1981, 1982, 1987 and 1989. Effects on reproductive function in rats were observed, with no-effect level of 0.5 mg TBA/kg diet. No evidence was found for a teratogenic potential of TBA in rats. From the results of in vitro as well as in vivo mutagenicity assays it was concluded that TBA was probably not genotoxic and that the increased tumour incidence observed in long-term studies in mice and rats arose as a consequence of the hormonal activity of TBA. The concentration of sex hormones in the circulation was significantly reduced and histopathological abnormalities (particularly in testes, ovaries and uteri) were observed in male and female pigs fed with high doses of TBA. The marginal no-effect level for these effects was 0.1 mg/kg diet, equal to approximately 2 micrograms/kg bw. The 34th JECFA meeting established an acceptable daily intake of 0-0.02 micrograms/kg bw of TBA.

Anabolic Agents↗

Olestra: a new food additive.

In 1987, Procter and Gamble Company (Cincinnati, Ohio) petitioned the US Food and Drug Administration (FDA) to amend the food additive regulations to allow sucrose esterified with fatty acids (olestra) to be used as a replacement for conventional fats. The petitioner later restricted its request for use in savory snacks. FDA considered evidence submitted by the petitioner, the opinions of experts, proceedings from the FDA Food Advisory Committee, and public discussion and concluded on January 25, 1996, that olestra was safe for use in savory snacks (eg, salty snacks such as potato chips, corn chips). Olestra is not toxic, carcinogenic, genotoxic, or teratogenic and is neither absorbed nor metabolized by the body, but may be associated with gastrointestinal tract symptoms such as cramping or loose stools. In addition, olestra affects the absorption of fat-soluble vitamins but does not affect the absorption of water-soluble nutrients. The petitioner's studies concluded that when olestra was consumed with foods containing vitamins A, D, E, or K, the fat substitute could have an effect on the absorption of these nutrients. Therefore, FDA is requiring that fat-soluble vitamins lost through absorption be added back to olestra as follows: 170 IU vitamin A per gram olestra, 12 IU vitamin D per gram olestra, 2.8 IU vitamin E per gram olestra, and 8 micrograms vitamin K per gram olestra. As part of the conditions of approval FDA is requiring that the food labels of products containing olestra disclose the vitamin compensation and the potential gastrointestinal effects. FDA is also requiring that further studies examining consumption patterns and the effects of olestra on human beings be conducted.

Digestive System↗

Evidence for the safety of gum karaya (Sterculia spp.) as a food additive.

Gum karaya (GK), accepted as Generally Recognised as Safe (GRAS) in the USA since 1961, was accepted temporarily (Annex II) as a food additive by the EEC in 1974. Since then no adverse incident involving human health has been attributed to the ingestion of GK, which is used in extremely small amounts in foods. This report collates the evidence of safety now available and presents the data on Need, production tonnages and dietary intake levels.

Food Additives↗

An analysis of the incremental value of retaining brand-level information in food consumption databases in estimating food additive intake.

In the Dietary and Nutritional Survey of British Adults (DNSBA) food consumption database, brand level intake data are recorded for 2197 subjects over 7 days. This study set out to examine the incremental value of such brand level data in food consumption studies to estimate additive intake. The food codes in the DNSBA database were re-arranged into 14 food categories within each of which were varying numbers of both sub-categories of foods and of brands. Intake of the 97.5th percentile for brands and sub-categories were compared with intakes at the 97.5th percentile of the appropriate food category. Taking > or = 60 consumers as the minimal sample size for which a 97.5th percentile statistic can be calculated, only 6% of the 1363 brands listed had sufficient data to work with. Of the 14 food categories, six had a sub-category with a 97.5th percentile in excess of that of the category but none exceeded 1.3 x 97.5th percentile intake of the category. Of the 85 brands for which there were > or = 60 consumers, only 11 had 97.5th percentile intakes in excess of that statistic for the relevant food category and none exceeded a multiple of 1.3 times the category 97.5th percentile intakes. Unless dietary surveys are very large and carried out for longer periods of time, there is little value in retaining food consumption data at brand level. If 1.3x the intake of an additive from a given food category at the 97.5th percentile does not exceed the ADI, no sub-category or brand appears to do so. This may provide a valuable technique in crude estimates of food additive intake.

Adolescent↗

alpha- and beta-Thujones (herbal medicines and food additives): synthesis and analysis of hydroxy and dehydro metabolites.

Essential oils containing alpha- and beta-thujones are important herbal medicines and food additives. The thujone diastereomers are rapidly metabolized convulsants acting as noncompetitive blockers of the gamma-aminobutyric acid-gated chloride channel. Synthesis and analysis of the metabolites are essential steps in understanding their health effects. Oxidation of alpha- and beta-thujones as their 2,3-enolates with oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide) gave the corresponding (2R)-2-hydroxythujones assigned by (1)H and (13)C NMR and X-ray crystallography. alpha-Thujone was converted to 4-hydroxy-alpha- and -beta-thujones via the 3,4-enol acetate on oxidation with peracid and osmium tetroxide, respectively. Ozonation provided 7-hydroxy-alpha- and -beta-thujones, and by dehydration provided the 7,8-dehydro compounds. 4,10-Dehydrothujone was prepared from sabinene via sabinol. The hydroxy and dehydro derivatives are readily identified and analyzed by GC/MS as the parent compounds and trimethylsilyl and methyloxime derivatives. A separate study established that all of these compounds are metabolites of alpha- and beta-thujones.

Bicyclic Monoterpenes↗

Immunogenicity of foods and food additives--in vivo testing of gums arabic, karaya and tragacanth.

An inexpensive animal model is described, for investigation of the immunogenicity of substances such as food additives. Inbred mice were immunised with antigen emulsified in complete Freund's adjuvant, and specific cell-mediated immunity subsequently measured by a footpad swelling test. This method has been applied in an investigation of the immunogenicity of the exudate gums, gum arabic, gum karaya and gum tragacanth. These substances are capable of eliciting an immune response which is comparable to the specific immune responses elicited by a protein antigen, e.g. hens' egg ovalbumin. Purification of commercially available gum preparations led to a significant (P less than 0.005) reduction of the immune response under in vivo test conditions.

Allergens↗