Are food additives messing with your hormones?

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Guest post by Maricel Maffini, Ph.D

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 FDA’s Priority-based Assessment of Food Additives, or PAFA, database is woefully incomplete and outdated.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. For more tips: http://www.breastcancerfund.org/reduce-your-risk/tips/eat-live-better/. 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

 

 maricelMaricel Maffini is a private contractor on issues related to chemical safety, food additive regulation, science and public health.

 

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