Estrogenicity of the syntheic food colorants tartrazine, erythrosin B, and sudan I in an estrogen-responsive human breast cancer cell line.(Report)

ABSTRACT--We investigated the estrogenic activity of three synthetic food colorants using two in vitro assays in estrogen receptor positive T47D breast cancer cells. Specifically, we examined whether tartrazine (FD & C Yellow No. 5), erythrosin B (FD & C Red No. 3), and sudan I in nanomolar ranges could mimic estradiol-17[beta] (E2). Using E-screen assays, we detected the highly significant proliferative effects (PE) of tartrazine (P = 0.0004), erythrosin B (P

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Synthetic colorants are used to make foods more appealing to consumers, create distinctive colorations for medicines, and develop various shades in facial cosmetics. However, studies have revealed toxicological effects of many colorants. In vitro carcinogenicity of sudan I has been revealed in Salmonella typhimurium (Cameron et al., 1987; Zeiger et al., 1988) and mouse lymphoma L5178Y TK+/- cells (Cameron et al., 1987). In 1991, Westmoreland and Gatehouse revealed the clastogenic properties of sudan I in an vivo rodent micronuclei test;, more recent studies have suggested possible carcinogenicity in humans through the formation of DNA adducts (dose range 0.1-100 [micro]M) (Stiborova et al., 2002). In addition, Kozuka et al. (1980) have shown that sudan I is a causative agent for pigmented contact dermatitis in humans. Currently, sudan I is a banned food colorant due to its carcinogenic properties. Erythrosin B (FD & C Red No. 3) has been shown to effect acetylcholine release at the neuromuscular junction, in vivo (Augustine and Levitan, 1983). In studies of chronically exposed male rats (28 months, 4% of diet), erythrosin B resulted in a significantly higher incidence of thyroid follicular cell adenomas and carcinomas (Food and Drug Administration, 1990). More necently, erythrosin B (dose range: 25-100 [micro]g/mL) has been shown to stimulate proliferation in estrogen receptor (ER) positive HTB 133 cells and to increase Cdk2 activity (dose range: 3-10 [micro]g/mL) in MCF7 cells (Dees et al., 1997). Additionally, Dees et al., (1997) suggest both erythrosin B and tartrazine (FD & C Yellow No. 5) may damage DNA as evidenced by increased p53-DNA binding in MCF7 cells treated with these compounds, though the reported effect of tartrazine was relatively low. Tartrazine has been reported to cause urticaria, asthma, and in some cases a cross-sensitivity in aspirin and NSAID-sensitive individuals (Dipalma, 1990). The mode of action of tartrazine is still under investigation, and it has been categorized as a pseudo-allergen (Dipalma, 1990).

Acceptable daily intake (ADI in mg/kg body weight) is the amount of a food additive that can be consumed daily wihtout appreciable risk based on all available toxicological data. The ADI for a food additive is generally calculated by dividing the "no observable adverse effect level" or NOAEL in animal studies by a large factor such as 100 and is established in the United States by the Food and Drug Administration (FDA). A review of toxicological data for sudan I has rendered it a banned food additive (i.e., ADI = 0 mg/kg body weight). Erythrosin B is approved in the United States for food and ingested drugs with an ADI of 2.5 mg/kg body weight (Lipman, 1995). The gastric absorption rate of (131) I-erythrosin has been estimated to be approximately 1% or less in humans (unpublished study reviewed in FDA, 1990). Tartrazine is approved in the United States for food, drug, and cosmetic use at an ADI of 5 mg/kg body weight (FDA, 1985). Gastric absorption of tartrazine has not been determined in humans, but in rats the gastric absorption data appear similar to data for erythrosin B with approximately 1% or less being absorbed (Honohan et al., 1997). Tartrazine is also found as an active ingredient in aquatic herbicides such as Aquashade. Depending on the particular preparation of aquatic herbicide used, the Environmental Protection Agency (EPA) estimates concentrations of tartrazine to be 0.0023-0.048 mg/L in the body of water to which the preparation has been applied (EPA, 2005). Maximum exposure for terrestrial wildlife through drinking herbicide treated water is estimated at 0.0024 mg per day (0.1 mg Aquashade by 2.39% tartrazine in product) (EPA, 2005).

Endocrine disrupting chemicals (EDCs) mimic and disrupt the signaling cascade of endogenous hormones and, unlike classical poisons, act at low concentrations (Dickerson and Gore, 2007). Hormones are biologically effective in nanogram to microgram quantities; thus, very low concentrations of compounds that mimic endogenous hormones could have biological effects. Given the ADIs and estimated environmental concentrations, low absorption rates such as 1% could still result in body burdens in the nanomolar to micromolar range for erythrosin B and tartrazine. For example, if a 25 kg child consumed 1% of the ADI for tartrazine and 1% of that amount was absorbed, estimated blood concentrations would be 0.0083 mg/L or 15.6 nM (tartrazine MW = 534.36). The same calculation for erythrosin B yields an estimate of 4.74 nM (erythrosin B MW = 879.86).

Xenoestrogens are synthetic chemicals that specifically mimic and disrupt the signaling cascade of estrogens causing reproductive abnormalities in humans and wildlife. In 1979, ...