Are Food Additives Messing With Your Hormones?

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 FDA’s Priority-based Assessment of Food Additives, or PAFA, database is woefully incomplete and outdated.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.

Source: freepik.com

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.

Source: cen.acs.org

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