Table 1.
Food additive testing and challenge procedures
| Food Additive | Substance | Testing | OFC Vehicle | OFC Dose (every 20–30 min, unless specified) |
|---|---|---|---|---|
| Annatto | Annatto | SPT 1:1000 of dye or Gouda122; 2.33 g annatto seed powder in 5 mL saline solution SPT26; SPT 1:10,000, 1:1000, 1:10 with irritant at full strength annatto extract from General Mills (Minneapolis, MN) 27; ssIgE annatto seed (Bixa orellana) | Capsule | ADI117: bixin 0–12 mg/kg BW; norbixin 0–0.6 mg/kg BW117 |
| Aspartame | Aspartame | No validated skin tests; no commercially available IgE | Capsule | ADI: 0–40 mg/kg BW117; 100, 200, 400, 800 mg5; 50 mg123; >40 kg: dosing every 2 hr of 50 mg aspartame, 300 mg aspartame, 600 mg aspartame, and conversion products (7.5 mg β-aspartame, 15 mg aspartylphenylalanine diketopiperazine); <40 kg: half dosing31 |
| Carmine | Red coloring from cochineal insect: dye provided by company that manufactures Campari42; commercially available carmine 0.5% (Brial Allergen GmbH, Greven Germany)42 | 10% solution carmine powder in PBS, agitate at 4° C for 2 hr and dialyze against purified water and pass through 0.22-μ filter124; SPT 0.1% E120, carmine 0.5%42; carmine 5 mg/mL45; vitamin capsule powder diluted 0.1 mg/mL for SPT125; dried insects (Dactylopius coccus) were purchased (http://www.cochinealdye.com/index.html), pulverized and then suspended 1:10 by weight in tap water, incubated and agitated at 80° C for 15 min in a water bath; color values were measured by absorption spectrometry and diluted to a color value of 0.1 (~0.5 μg protein/mL), 0.01, 0.001 by using PBS, and then filtered through a 0.2-μm syringe filter37; undiluted food grade carmine dye (≥3.5% carminic acid) obtained from Warner Jenkinson (a Sensient company, St. Louis, Missouri)126 and Good Humor company's supplier43; ssIgE carmine (Cochineal dactylopius) | Capsule | ADI: 0–5 mg/kg BW117; 1, 5, 10, 15 mg5 |
| Carob bean gum | Carob gum (raw or boiled bum, bean extract) | 5, 15, 25 mg/mL127; ssIgE carob gum/locust bean | Capsule | ADI: not specified117 |
| Carrageenan | Sodium carrageenan | 0.4% w/v sodium carrageenan (Sanofi Bio-Industries, Mississauga, Ontario, Canada) may be more reliable than carrageen gum (1:50 w/v, Miles Inc., Canada) 48; ssIgE carrageenan | Capsule | ADI: not specified117 |
| Dyes (see specifics for annatto above and tartrazine below) | FD&C dyes | No validated tests128; ssIgE amaranth/FD&C red no. 2; no ssIgE for other dyes (except carmine, see above) | Capsule | ADI117: not specified benzyl violet 4B, FD&C green no. 1 and 2, FD&C red no. 4 and 40/Allura, FD&C violet no. 1; FD&C blue no.1/brilliant blue: 0–6 mg/kg BW; FD&C blue no. 2/indigo: 0–5 mg/kg BW; FD&C green no. 3/fast green: 0–25 mg/kg BW; FD&C red no. 2/amaranth: 0–0.5 mg/kg BW; FD&C red no. 3/erythrosine: 0–0.1 mg/kg BW; FD&C yellow no. 6/sunset yellow: 0–4 mg/kg BW; 1, 5, 10, 15 mg5; 5, 20 mg each118 |
| Erythritol | Erythritol | 2 mg/mL, 20 mg/mL, 200 mg/mL in distilled water129; SPT 100 mg/mL in 50% glycerin, IDT positive between 160 and 20 mg/mL (nonirritating up to 100 mg/mL)51; no ssIgE | Capsule | ADI: not specified117; 100, 200, 400, 800 mg each5 |
| Gelatin | Gelatin | 1 tsp (5 g) of gelatin in 5 mL normal saline solution130; ssIgE gelatin | Capsule | ADI: not limited117 |
| Guar gum | Guar gum | 1 mg of guar gum in 1 mL PBS (0.12 mg/mL), mixed for 2 hr at room temperature and centrifuged, with removal of supernatant, stored at –20° C until use131; ssIgE guar (bean) gum | Capsule or particles for inhalation | ADI: not specified117; inhalation challenge (reactions of patients with asthma): lactose control (15 min of exposure) on day 1, guar gum (progressive: one breath, 15 sec, 45 sec, 2 min) on day 2; positive, with PEV decreased by ≥20%; spirometry pre-exposure, and every 10 min × 60 min, then every 30 min × 60 min, then every hour × 7–8 hr131 |
| Mannitol | d-Mannitol | SPT alditol-protein conjugates dialyzed against PBS at 4° C sterile filtered and used for SPT 1% w/v (10 mg/mL) 1:10 and full strength109; SPT 20% (Isotol, Diaco Biofarmaceutici Industry, Trieste, Italy), 1:10 ID76 | ADI: not specified117; mannitol laxative 1 mg/mL, 3 mg/mL, 10 mg/mL every 1 hr76 | ADI: not specified117; mannitol laxative 1, 3, 10 mg/mL every 1 hr76 |
| MSG | MSG powder | 100 mg/mL in NS119; no ssIgE available | Capsule or citrus drink | ADI: not specified117; 200, 400, 800, 1600 mg5; single dose of 5 g132; single dose of 2.5 g133; 100 mg, 500 mg, 1 g, 6 g (total 7.6 g) every 30 min134 |
| Preservatives, other | Sodium benzoate, BHA, BHT, parabens (methyl-, ethyl-, butyl-), sorbate (methyl-, ethyl-, propyl-, allyl), polyoxyethylene sorbitan stearate, polysorbate (20, 40, 60, 65, 80), potassium–sodium sorbate, potassium–sodium nitrite, polyethylene glycol | Polysorbate 100% SPT, 1:10 IDT (neg pt and control), undiluted (pos pt, not tested in control)135; PEG 300 and 3350 1:100 and 1:10 SPT136; polysorbate 80 eye drop (1:10) IDT136; methylparaben 0.1% SPT; also methylparabencontaining local anesthetics with FS SPT, IDT 0.04 mL 1:100137; no ssIgE; basophil function sodium nitrite available; patch tests available – *NACDG panel (paraben mix 12% petrolatum, polysorbate 80 5% pet, BHA 2% pet); *Chemotechnique: sodium benzoate, BHT | Capsule | ADI117: sodiumbenzoate: 0–5 mg/kg BW; BHA: 0–0.5 mg/kg BW; BHT: 0–0.3 mg/kg BW; methyl-, ethylparabens: 0–10 mg/kg BW; butylparaben; methyl-/ethyl-/propyl-/allyl sorbate: no safety concern at current levels of intake when used as flavoring agent; polyoxyethylene sorbitanmono-oleate/palmitate/laurate/stearate or tristearate: 0–25 mg/kg BW; polysorbate 20/40/60/65/80: 0–25 mg/kg BW; potassium, sodiumsorbate: 0–25 mg/kg; (potassium, sodium) nitrite: 0–0.7 mg/kg BW; polyethylene glycols: 1–10 mg/kg BW; all: 25, 50, 100, 200 mg5; BHA, BHT: 125, 250 mg each118; sodium benzoate: 50, 100, 250 mg118; parabens (anesthetic allergy): 1 mL SC NS placebo, 1 mL SC undiluted local anesthetic137 |
| Psyllium | Psyllium powder | SPT 2.5% w/v dissolved in 50% glycerol138; ssIgE psyllium (ispaghula) available | Powder or capsule | ADI not listed117; inhalation challenge: tipping psyllium powder from one tray to another for 5, 15, 45 sec, and 2 min × 2 with serial FEV1 measurements immediately, 10 min after exposure and every 10 min × 1 hr, every 30 min × 1 hr for up to 8 hr; positive if FEV1 decreases ≥ 20%; if no change, exposure increased to 30 min on a separate day138; oral challenge: 0.1, 0.5, 2 g every 30 min139 |
| Tartrazine (FD&C yellow no. 5) | Tartrazine powder | No validated skin tests128; basophil function tartrazine available | Capsule | ADI: 0–10 mg/kg BW117; placebo, tartrazine 25 mg and 50 mg every 3 hr140; 1, 5, 10, 15 mg5; 5, 20 mg118; 25 mg141; 1 mg, 10 mg6; 1, 5 15, 25, 50 mg61 |
| Sulfite | Potassium meta-bisulfite | 1 mg/mL SPT and IDT potassium metabisulfite103; sodium metabisulfite 10% w/v (dissolving carmine 10% in PBS for 2 hr at 4° C with gentle agitation, dialyzed against purified water and passed through 0.22-μ Millipore filter)124; no ssIgE available | Capsule or solution | ADI117: calcium (bisulfite, hydrogen sulfite, metabisulfite), disodium, potassium (hydrogen sulfite, metabisulfite, sulfite), sodium (disulfite, hydrogen sulfite, hyposulfite, metabisulfite, sulfite, thiosulfate): 0–0.7 mg/kg BW; caramel color class II, caustic sulfite caramel: 0–160 mg/kg BW; caramel color class IV, sulfite ammonia caramel: 0–200 mg/kg; 25, 50, 100, 200 mg5; 1, 5, 10, 25, 50 mg103; capsule and neutral solution challenge: 1, 5, 25, 50, 100, 200 mg capsules and then 1, 10, 25 mg in a water-sucrose solution every 30104; acidic solution challenge: 0.1, 0.5, 1, 5, 10, 15, 25, 50, 75, 100, 150, 200 mg/20 mL lemonade solution every 10 min104 |
| Scripps protocol: SPT 0.001, 0.01, 0.1, 1 mg/mL every 15 min; IDT 0.02 mL of 0.001 mg/mL | Solution (sulfitefree mix or fresh lemons); capsule | Solution: 10 mL, swish in mouth for several seconds and swallow: *1, 10, 25, 50, 100 mg every 20 min; *patients with asthma: placebo, 10, 50, 100 mg, and then placebo every 30 min; 1, 10, 25, 50, 100 mg every 30 min; for capsule and solution, spirometry before and after each dose | ||
| Sweetener (see specifics for erythritol, aspartame above) | Artificial (acesulfame, saccharin, sucralose); natural (corn syrup, fructose, glucose, sucrose) | No validated skin testing; ssIgE saccharin | Capsule | ADI117; acesulfame, sucralose: 0–15 mg/kg; saccharin: 0–5 mg/kg BW; sucrose acetate isobutyrate: 0–20 mg/kg BW; sucralose, trichlorogalactosucrose: 0–15 mg/kg BW; glucose, sucrose fatty acid esters: not specified; corn syrup, fructose not listed; 100, 200, 400, 800 mg each5; 40 mg saccharin in 120 mL water, 1 tsp sugar in 120 mL water, 80 mg saccharin in 120 mL water every 45 min142 |
| Yeast | Saccharomyces cerevisiae | SPT: 1 mg/mL, 10 mg/mL143; SPT commercial extract130; hepatitis B, human papillomavirus vaccine if a history of a reaction130; may be cross-reactive with Candida albicans143,144; ssIgE baker's yeast (S. cerevisiae) | Capsule (regular baker's yeast), solution (beer, wine) | ADI: not listed117; S. cerevisiae may be cross-reactive with C. albicans,29 with 95% of patients sensitized to C. albicans also being positive on skin testing with S. cerevisiae enolase143 |
OFC = Oral food challenge; SPT = skin-prick text; ssIgE = serum specific immunoglobulin E; ADI = acceptable daily intake; BW = Body weight; IgE = immunoglobulin E; DKP = diketopiperazine; PBS = phosphate-buffered saline; FD&C = Food, Dye, and Cosmetic Act; IDT = intradermal test; PEV = peak expiratory volume; MSG = monosodium glutamate; BHA = butylated hydroxyanisole; BHT = butylated hydroxytoluene; FS = full strength; NS = normal saline; PEG = polyethylene glycol; NACDG = North American Contact Dermatitis Group; SC = sub-cutaneous; FEV1 = forced expiratory volume in the first second of expiration. 117 Joint FAO/WHO Expert Committee on Food Additives: not specified = listed; not listed = unable to be found.