As the season of eating approaches, it’s a great opportunity to talk about chemicals in food. Although there are some familiar names such as bisphenol A (BPA), we don’t often hear about food additives and their association with breast health or disease. But before I dig in, there are three things I want you to know:
1. The FDA regulates chemicals allowed in food. There are approximately 10,000 chemicals that can be used directly or allowed to be present in food; for roughly 1,000 of those, FDA has no knowledge of their identity, how much or where they are being used. There are several legal categories but in general chemicals are:
• Direct additives: those knowingly added to food to preserve, provide flavor, etc.
• Indirect additives: these are chemicals that get into the food through the manufacturing, handling and packaging processes.
2. The ingredients listed in packaged food don’t tell the whole story of what really is in the food. For example, we don’t know how much and how many chemicals leach from the packaging into the food. And there are huge data gaps in the safety of food additives. The mammary gland is an organ not commonly evaluated in toxicology testing of environmental chemicals therefore data on the impact on breast is limited to a few chemicals investigated in academic institutions.
3. The normal development of the breast depends on the right balance of hormones and their timing. Disruption of the hormonal signaling by chemicals (usually called endocrine disruptors) will affect the normal shape and size of the gland and potentially increase the risk of breast cancer in adulthood. The impact is particularly greater when exposures occur during fetal development and puberty. Examples are BPA, DDT and PFOA.
Both BPA and PFOA are known endocrine disruptors and allowed in food. How many more food additives cause adverse effects in the breast? We don’t know; there isn’t a publicly available database of food additives toxic effects. FDA’s Priority-based Assessment of Food Additives, or PAFA, database is woefully incomplete and outdated. You may ask, how many food additives are endocrine disruptors then? Sorry, also unknown. FDA not only doesn’t have a list of endocrine disrupting food additives, it hasn’t defined endocrine disruption and doesn’t recommend screening chemicals for potential hormonal activity.
I used data released by the Tox21 program, a multi-agency effort between FDA, EPA and NIH that uses cell-based and biochemical assays to quickly and efficiently identify potential toxic effects for thousands of chemicals that lack information. I was interested in the estrogen receptor assay; estrogen is a crucial hormone in normal breast development and function.
Hormones such as estrogen bind to receptors to initiate a biological effect. But, other chemicals can also bind to the receptor and trigger a similar effect; these chemicals are called agonists. On the contrary, chemicals that prevent the hormone from binding to the receptor are called antagonists.
I found 223 food additives that reacted with the estrogen receptor alpha, 75% were agonists and 25% antagonists. The table below shows the additives breakdown. See tables 1 and 2 for full list of names.
| Food Additive | Agonists | Antagonists |
| Flavors | 61 (37%) | 3 (5%) |
| Other direct additives | 17 (10%) | 4 (7%) |
| Indirect/packaging additives | 64 (38%) | 18 (32%) |
| Pesticides | 25 (15%) | 31 (56%) |
| Total | 167 | 56 |
There were some known chemicals such as bisphenol A, parabens and the soy-derived genistein but the great majority were unknown to me. The great majority of these chemicals will not appear on any ingredient list; for instance, flavors are usually listed generically as artificial or natural flavors. Also, you won’t find a list of pesticide residues or packaging chemicals. And likely, most of these don’t have safety information available to the public.
But here is my point: the Food Additive Amendment of 1958 mandated that the FDA consider the cumulative effect of the substance in the diet, taking into account any chemically or pharmacologically related substance or substances in such diet (21 U.S.C. 348(c)(5) & 21 CFR §170.3(i)) when determining the safety of a chemical. In lay terms, “chemically related” means that the chemicals have a similar structure, and “pharmacologically related” means that the chemicals produce similar biological effects.
It’s clear from the data that there are 167 chemicals, which activate the estrogen receptor. And all of them have the potential to disrupt our hormone systems.
We don’t know how many are in our daily diets and we know close to nothing about their cumulative impact on mammary gland development and breast health.
While thousands of food additives have been allowed into use, the health impacts of chronic exposures to multiple chemicals affecting the same organs or systems has largely been ignored.
It’s time for the FDA to modernize its chemical safety assessment to routinely include screening for potential hormonal activity and the mammary gland as a sensitive organ for toxicity testing. And it should harness these new technologies to design a chemical safety reassessment program based on cumulative toxic effects.
What can you do? As a start, you can reduce exposures to chemicals in food by avoiding highly processed and canned foods, and choosing organic and hormone-free foods.
As consumers, we are responsible for educating ourselves and chose the best food for our families. However, it’s Congress and FDA’s responsibility to keep the food supply and all American families safe from potentially dangerous chemicals.
By reducing our exposure to chemicals in our food, we reduce our risk of disease. Let’s work to better educate ourselves, our families, friends and representatives that understanding the health impact of chronic exposures to multiple chemicals in the diet is critical to reduce the disease burden and improve the well-being of future generations.
Table 1 Chemicals allowed in food that are classified as estrogen receptor agonists based on their activity in Tox21 assays
| Chemical Name | CAS | Tox21 Assay Result | Regulatory status |
| Hexadecanoic acid | 57-10-3 | ERa agonist | Flavor |
| Lycopene | 502-65-8 | ERa agonist | Flavor |
| Octadecanoic acid | 57-11-4 | ERa agonist | Flavor |
| Fumaric acid | 110-17-8 | ERa agonist | Flavor |
| Geraniol | 106-24-1 | ERa agonist | Flavor |
| Methyl salicylate | 119-36-8 | ERa agonist | Flavor |
| 3-Phenyl-2-propen-1-ol | 104-54-1 | ERa agonist | Flavor |
| Butylparaben | 94-26-8 | ERa agonist | Flavor |
| Phenethyl anthranilate | 133-18-6 | ERa agonist | Flavor |
| Piperine | 94-62-2 | ERa agonist | Flavor |
| Propylparaben | 94-13-3 | ERa agonist | Flavor |
| 2-Acetylthiazole | 24295-03-2 | ERa agonist | Flavor |
| 2-Benzylideneoctanal | 101-86-0 | ERa agonist | Flavor |
| 2-Phenylethyl 3-phenylprop-2-enoate | 103-53-7 | ERa agonist | Flavor |
| 2-Phenylethyl benzoate | 94-47-3 | ERa agonist | Flavor |
| 2-Thienyl disulfide | 6911-51-9 | ERa agonist | Flavor |
| 2-Tridecanone | 593-08-8 | ERa agonist | Flavor |
| 3,3-Dimethylacrylic acid | 541-47-9 | ERa agonist | Flavor |
| 3-Hexanone | 589-38-8 | ERa agonist | Flavor |
| 3-Methylbutyl cinnamate | 7779-65-9 | ERa agonist | Flavor |
| 3-Phenyl-2-propen-1-yl 3-phenylacrylate | 122-69-0 | ERa agonist | Flavor |
| 3-Phenylpropanal | 104-53-0 | ERa agonist | Flavor |
| 3-Phenylpropyl cinnamate | 122-68-9 | ERa agonist | Flavor |
| 4-Isopropylbenzyl alcohol | 536-60-7 | ERa agonist | Flavor |
| 4′-Methoxyacetophenone | 100-06-1 | ERa agonist | Flavor |
| 5-Methyl-2,3-hexanedione | 13706-86-0 | ERa agonist | Flavor |
| 5-Methyl-2-phenyl-2-hexenal | 21834-92-4 | ERa agonist | Flavor |
| alpha-Terpinyl acetate | 80-26-2 | ERa agonist | Flavor |
| Anise oil | 8007-70-3 | ERa agonist | Flavor |
| Benzenemethanethiol | 100-53-8 | ERa agonist | Flavor |
| Benzoic acid | 65-85-0 | ERa agonist | Flavor |
| Benzophenone | 119-61-9 | ERa agonist | Flavor |
| Benzyl cinnamate | 103-41-3 | ERa agonist | Flavor |
| Benzyl salicylate | 118-58-1 | ERa agonist | Flavor |
| Decyl acetate | 112-17-4 | ERa agonist | Flavor |
| Diallyl trisulfide | 2050-87-5 | ERa agonist | Flavor |
| Diisobutyl ketone | 108-83-8 | ERa agonist | Flavor |
| gamma-Caprolactone | 695-06-7 | ERa agonist | Flavor |
| Heptyl acetate | 112-06-1 | ERa agonist | Flavor |
| Isopropyl tetradecanoic acid | 110-27-0 | ERa agonist | Flavor |
| L-Ascorbic acid | 50-81-7 | ERa agonist | Flavor |
| Linalyl benzoate | 126-64-7 | ERa agonist | Flavor |
| Linalyl cinnamate | 78-37-5 | ERa agonist | Flavor |
| Methyl styryl ketone | 122-57-6 | ERa agonist | Flavor |
| Methyleugenol | 93-15-2 | ERa agonist | Flavor |
| Naphthalen-2-yl 2-aminobenzoate | 63449-68-3 | ERa agonist | Flavor |
| Pentanoic acid | 109-52-4 | ERa agonist | Flavor |
| Pentylcinnamaldehyde | 122-40-7 | ERa agonist | Flavor |
| Phenethyl isothiocyanate | 2257-09-2 | ERa agonist | Flavor |
| Phloretin | 60-82-2 | ERa agonist | Flavor |
| Piperazine | 110-85-0 | ERa agonist | Flavor |
| Propyl gallate | 121-79-9 | ERa agonist | Flavor |
| Sodium saccharin | 128-44-9 | ERa agonist | Flavor |
| Styrax balsam | 8046-19-3 | ERa agonist | Flavor |
| Terpinolene | 586-62-9 | ERa agonist | Flavor |
| Tetradecanal | 124-25-4 | ERa agonist | Flavor |
| Triacetin | 102-76-1 | ERa agonist | Flavor |
| Undecanal | 112-44-7 | ERa agonist | Flavor |
| Veratraldehyde | 120-14-9 | ERa agonist | Flavor |
| (2E)-3-Phenylprop-2-enal | 14371-10-9 | ERa agonist | Flavor |
| D-Lactic acid | 10326-41-7 | ERa agonist | Flavor |
| Docusate sodium | 577-11-7 | ERa agonist | Direct additive |
| Heptylparaben | 1085-12-7 | ERa agonist | Direct additive |
| 1,3-Butanediol | 107-88-0 | ERa agonist | Direct additive |
| Canthaxanthin | 514-78-3 | ERa agonist | Direct additive |
| Ergocalciferol | 50-14-6 | ERa agonist | Direct additive |
| Ethylenediamine | 107-15-3 | ERa agonist | Direct additive |
| Folic acid | 59-30-3 | ERa agonist | Direct additive |
| Glycocholic acid | 475-31-0 | ERa agonist | Direct additive |
| Polyethylene glycol di-(9Z)-9-octadecenyl ether | 9005-07-6 | ERa agonist | Direct additive |
| Rutin trihydrate | 153-18-4 | ERa agonist | Direct additive |
| Tetrasodium pyrophosphate | 7722-88-5 | ERa agonist | Direct additive |
| Daidzein | 486-66-8 | ERa agonist | GRAS |
| Genistein | 446-72-0 | ERa agonist | GRAS |
| Resveratrol | 501-36-0 | ERa agonist | GRAS |
| alpha-Cyclodextrin | 10016-20-3 | ERa agonist | GRAS |
| Glucosamine hydrochloride | 66-84-2 | ERa agonist | GRAS |
| Quercetin | 117-39-5 | ERa agonist | GRAS |
| Bisphenol A | 80-05-7 | ERa agonist | Indirect/packaging |
| 2,2,4-Trimethyl-1,3-pentanediol diisobutyrate | 6846-50-0 | ERa agonist | Indirect/packaging |
| 2-Hydroxyethyl acrylate | 818-61-1 | ERa agonist | Indirect/packaging |
| 4-Chloro-3-methylphenol | 59-50-7 | ERa agonist | Indirect/packaging |
| Sodium dichloroisocyanurate | 2893-78-9 | ERa agonist | Indirect/packaging |
| Triisopropanolamine | 122-20-3 | ERa agonist | Indirect/packaging |
| Pentaerythritol tetrakis(3,5-di-tert-butyl-4-hydroxyhydrocinnamate) | 6683-19-8 | ERa agonist | Indirect/packaging |
| Nonanedioic acid | 123-99-9 | ERa agonist | Indirect/packaging |
| 2-(2H-Benzotriazol-2-yl)-4-methylphenol | 2440-22-4 | ERa agonist | Indirect/packaging |
| 2-Hydroxy-4-methoxybenzophenone | 131-57-7 | ERa agonist | Indirect/packaging |
| 4-(2-Methylbutan-2-yl)phenol | 80-46-6 | ERa agonist | Indirect/packaging |
| 4-(Benzyloxyl)phenol | 103-16-2 | ERa agonist | Indirect/packaging |
| 4,4′-Sulfonyldiphenol | 80-09-1 | ERa agonist | Indirect/packaging |
| 4-Cumylphenol | 599-64-4 | ERa agonist | Indirect/packaging |
| 4-Nonylphenol | 104-40-5 | ERa agonist | Indirect/packaging |
| Benzamide, N,N’-(dithiodi-2,1-phenylene)bis- | 135-57-9 | ERa agonist | Indirect/packaging |
| Bisphenol B | 77-40-7 | ERa agonist | Indirect/packaging |
| Butyl benzyl phthalate | 85-68-7 | ERa agonist | Indirect/packaging |
| Di(propylene glycol) dibenzoate | 27138-31-4 | ERa agonist | Indirect/packaging |
| Dicumyl peroxide | 80-43-3 | ERa agonist | Indirect/packaging |
| Dodecylphenol | 27193-86-8 | ERa agonist | Indirect/packaging |
| Ethylparaben | 120-47-8 | ERa agonist | Indirect/packaging |
| N-Phenyl-1-naphthylamine | 90-30-2 | ERa agonist | Indirect/packaging |
| N-Phenyl-2-naphthylamine | 135-88-6 | ERa agonist | Indirect/packaging |
| Phenothiazine | 92-84-2 | ERa agonist | Indirect/packaging |
| (1,1,3,3-Tetramethylbutyl)phenol | 27193-28-8 | ERa agonist | Indirect/packaging |
| 1,2,3-Trichloropropane | 96-18-4 | ERa agonist | Indirect/packaging |
| 1,3-Propanediol, 2,2-dimethyl-, dibenzoate | 4196-89-8 | ERa agonist | Indirect/packaging |
| 2-(Dimethylamino)-2-methylpropan-1-ol | 7005-47-2 | ERa agonist | Indirect/packaging |
| 2-Naphthalenol | 135-19-3 | ERa agonist | Indirect/packaging |
| 2-tert-Butyl-4-ethylphenol | 96-70-8 | ERa agonist | Indirect/packaging |
| 4,4′-Dimethoxydiphenylamine | 101-70-2 | ERa agonist | Indirect/packaging |
| 4-Octylphenol | 1806-26-4 | ERa agonist | Indirect/packaging |
| 4-tert-Butylcatechol | 98-29-3 | ERa agonist | Indirect/packaging |
| 4-tert-Butylphenyl salicylate | 87-18-3 | ERa agonist | Indirect/packaging |
| 4-Undecanol, 7-ethyl-2-methyl-, hydrogen sulfate, sodium salt | 139-88-8 | ERa agonist | Indirect/packaging |
| 6-Phenyl-1,3,5-triazine-2,4-diamine | 91-76-9 | ERa agonist | Indirect/packaging |
| Ammonium nitrate | 6484-52-2 | ERa agonist | Indirect/packaging |
| Bumetrizole | 3896-11-5 | ERa agonist | Indirect/packaging |
| Butyl benzoate | 136-60-7 | ERa agonist | Indirect/packaging |
| Cresyl diphenyl phosphate | 26444-49-5 | ERa agonist | Indirect/packaging |
| Dibutyl phthalate | 84-74-2 | ERa agonist | Indirect/packaging |
| Diisobutyl phthalate | 84-69-5 | ERa agonist | Indirect/packaging |
| Diphenolic acid | 126-00-1 | ERa agonist | Indirect/packaging |
| Diundecyl phthalate | 3648-20-2 | ERa agonist | Indirect/packaging |
| Dodecanedioic acid | 693-23-2 | ERa agonist | Indirect/packaging |
| Ethylene acrylate | 2274-11-5 | ERa agonist | Indirect/packaging |
| Glyoxal | 107-22-2 | ERa agonist | Indirect/packaging |
| Iodoform | 75-47-8 | ERa agonist | Indirect/packaging |
| N-(2-Hydroxyethyl)acetamide | 142-26-7 | ERa agonist | Indirect/packaging |
| N,N’-Diphenyl-p-phenylenediamine | 74-31-7 | ERa agonist | Indirect/packaging |
| N-Oxydiethylenebenzothiazole-2-sulfenamide | 102-77-2 | ERa agonist | Indirect/packaging |
| Potassium perchlorate | 7778-74-7 | ERa agonist | Indirect/packaging |
| Sodium persulfate | 7775-27-1 | ERa agonist | Indirect/packaging |
| Toluene-2,4-diisocyanate | 584-84-9 | ERa agonist | Indirect/packaging |
| Tributyl phosphate | 126-73-8 | ERa agonist | Indirect/packaging |
| Triphenyl phosphate | 115-86-6 | ERa agonist | Indirect/packaging |
| 4-Phenylphenol | 92-69-3 | ERa agonist | Indirect/packaging |
| 1,3-Dichloro-5,5-dimethylhydantoin | 118-52-5 | ERa agonist | Indirect/packaging |
| Ethyl 2-cyano-3,3-diphenylacrylate | 5232-99-5 | ERa agonist | Indirect/packaging |
| 4,4′-Biphenyldiol | 92-88-6 | ERa agonist | Indirect/packaging |
| C.I. Solvent red 24 | 85-83-6 | ERa agonist | Indirect/packaging |
| Isooctyl acrylate | 29590-42-9 | ERa agonist | Indirect/packaging |
| Phenol red | 143-74-8 | ERa agonist | Indirect/packaging |
| Carboxin | 5234-68-4 | ERa agonist | Pesticide |
| Clofentezine | 74115-24-5 | ERa agonist | Pesticide |
| Thiabendazole | 148-79-8 | ERa agonist | Pesticide |
| (Z)-11-Hexadecenal | 53939-28-9 | ERa agonist | Pesticide |
| Acifluorfen-sodium | 62476-59-9 | ERa agonist | Pesticide |
| Benomyl | 17804-35-2 | ERa agonist | Pesticide |
| Carbofuran | 1563-66-2 | ERa agonist | Pesticide |
| Cyprodinil | 121552-61-2 | ERa agonist | Pesticide |
| Desmedipham | 13684-56-5 | ERa agonist | Pesticide |
| Diflubenzuron | 35367-38-5 | ERa agonist | Pesticide |
| Ethion | 563-12-2 | ERa agonist | Pesticide |
| Fenarimol | 60168-88-9 | ERa agonist | Pesticide |
| Fenhexamid | 126833-17-8 | ERa agonist | Pesticide |
| Fenoxaprop-ethyl | 66441-23-4 | ERa agonist | Pesticide |
| Fenthion | 55-38-9 | ERa agonist | Pesticide |
| Fenvalerate | 51630-58-1 | ERa agonist | Pesticide |
| Fluazifop-P-butyl | 79241-46-6 | ERa agonist | Pesticide |
| Hydramethylnon | 67485-29-4 | ERa agonist | Pesticide |
| Methyl parathion | 298-00-0 | ERa agonist | Pesticide |
| Norflurazon | 27314-13-2 | ERa agonist | Pesticide |
| Oxamyl | 23135-22-0 | ERa agonist | Pesticide |
| Pendimethalin | 40487-42-1 | ERa agonist | Pesticide |
| Phorate | 298-02-2 | ERa agonist | Pesticide |
| Spirodiclofen | 148477-71-8 | ERa agonist | Pesticide |
| Tralkoxydim | 87820-88-0 | ERa agonist | Pesticide |