Safety and Benefits

of Food Colors
Sean Taylor, PhD
Managing Director
Verto Solutions

Joseph Borzelleca, PhD

Professor, Pharmacology & Toxicology
VCU School of Medicine
 Overview of Presentation
About IACM
History of FD&C colors
Safety of FD&C colors
Colors have not been proven to cause
hyperactive behavior
Colors: important ingredients
IACMs Mission

to actively represent the interests of the color

industry by demonstrating the safety of color
additives, and to promote the industry's economic
growth by actively participating in new color
approvals and regulatory and legislative issues
that affect the industry worldwide
Current Members
 History of Color Additives in the US
Legal Framework
Colors are food additives under 1958 Food,
Drug, and Cosmetics Act
All color additives require pre-market approval
via color petition process
Colors listed in US Code of Federal Regulations,
Part 21, Section 73 & 74
 Certified & Exempt Colors

Colors can be generally divided into

certified and exempt from certification
categories
Certified: Testing of each batch by FDA
confirms safety
Exempt colors: no batch testing required

Certified colors: FD&C colors

 Certified Colors (21 CFR 74)

Certified color Uncertified name

FD&C Red No. 40 Allura Red AC
FD&C Red No. 3 Erythrosine
FD&C Blue No. 1 Brilliant Blue FCF
FD&C Blue No. 2 Indigotine
FD&C Yellow No. 5 Tartrazine
FD&C Yellow No. 6 Sunset Yellow FCF
FD&C Green No. 3 Fast Green FCF
 Exempt Colors (21 CFR 73)
Annatto extract Haematococcus algae meal
Astaxanthin Synthetic iron oxide
Dehydrated beets (beet powder) Fruit juice
Ultramarine blue Vegetable juice
Canthaxanthin Dried algae meal
Caramel Tagetes (Aztec marigold) meal
beta-Apo-8'-carotenal and extract
beta-Carotene Carrot oil
Cochineal extract; carmine Corn endosperm oil
Sodium copper chlorophyllin Paprika/oleoresin (extract)
Toasted partially defatted cooked Phaffia yeast
cottonseed flour Riboflavin
Ferrous gluconate Saffron
Ferrous lactate Titanium dioxide
Grape color extract Turmeric/oleoresin
Grape skin extract (Enocianina)
 Safety of FD&C Colors
Approval process in US
Color additive petition filing
Specifications/purity
Use/technological justification
Toxicological data
FDA Redbook requirements
Exposure
FDA review/public comment process
Final rulemaking with allowed use
 Food additive petition:
FDA recommended toxicity testing
Concern Level Concern Level Concern Level
Toxicity Tests Low (I) Intermediate (II) High (III)
Genetic Toxicity Tests X X X

Short-term toxicity tests with rodents X X X

Subchronic toxicity studies with rodents X X

Subchronic toxicity studies with non-rodents X X

One-year toxicity studies with non-rodents X

Chronic toxicity or Combined chronic
X
toxicity/carcinogenicity studies with rodents
Carcinogenicity studies with rodents X

Reproduction studies X X

Developmental toxicity studies X X

Metabolism and Pharmacokinetic studies X X

Human studies X
 Safety of FD&C Colors in the US
Color Risk Assessment
Substantial safety datasets for many colors
FDA review led to listing as allowed colors
WHO/FAO JECFA Review
establish acceptable daily intakes (ADIs)
Additional data collected
Genotoxicity
Allergenicity
other studies
 Safety of FD&C Colors in the US
FD&C Blue No. 1 and Green No. 3
Name of color FD&C Blue No. 1 FD&C Green No.
(Brilliant Blue FCF) 3
(Fast Green
FCF)
In use since 1929 1927
Genetox In Vitro/In Vivo In Vitro/In Vivo
Acute/Subchronic Rats Rats
Chronic Rats/Mice Rats/Mice
Carcinogenicity Rats/Mice Rats/Mice
Reproductive/Teratoge
Rats & Rabbits Rats & Rabbits
nic
Special studies
Human studies
ADMEK Diverse animals Rats
JECFA ADI (mg/kg/d) 0-12.5 0-25
Safety of FD&C Colors in the US
FD&C Blue No. 2
Name of color FD&C Blue No. 2
(Indigotine)
In use since 1907
Genetox In vitro/In vivo
Acute/Subchronic Rat, Mouse/90-day
Chronic Rats/Mice
Carcinogenicity Rats/Mice
Reproductive/Teratoge
Rats & Rabbits
nic
Special studies
Human studies
ADMEK Rats
JECFA ADI (mg/kg/d) 0-17
Safety of FD&C Colors in the US
FD&C Red No. 3
Name of color FD&C Red No. 3
(Erythrosine)
In use since 1907
Genetox In vitro/In vivo
Acute/Subchronic Rat, Mouse
Chronic Rats/Mice
Carcinogenicity Rats/Mice
Reproductive/Teratoge
Rats
nic
Thyroid/Mechanism of
Special studies
Action
Human studies Thyroid
ADMEK Rats, Humans
JECFA ADI (mg/kg/d) 0-0.1
 Safety of FD&C Colors in the US
The Azo dyes: Red 40, Yellow 5, Yellow 6
Name of color FD&C Red No. FD&C Yellow FD&C Yellow
40 No. 5 No. 6
(Allura Red (Tartrazine) (Sunset Yellow
AC) FCF)
In use since 1971 1916 1929
Genetox In vitro/In vivo In vitro/In vivo In vitro/In vivo
Acute/Subchronic Animals Mice R,M/90d
Chronic Rats/Mice Rats/Mice Rats/Mice
Carcinogenicity Rats/Mice Rats/Mice Rats/Mice
Reproductive/Teratolog
Rats/Mice Rats & Rabbits Rats
ical
Special studies Allergenicity Allergenicity
Human studies Allergenicity Allergenicity
Humans, Humans,
ADMEK Dogs, rats
Animals Animals

JECFA ADI (mg/kg/d) 0-7 0-7.5 0-2.5

 No Proven Causality to Hyperactivity
Historical perspective

Some research has suggested a link

between intake of food colors and
hyperactive behavior in children
Feingold diet
Hyperactivity studies (e.g., Isle of Wight)
Meta-analyses (e.g., Schab and Trinh)

Nutrition Foundation: no links

National Research Council: no links

 No Proven Causality to Hyperactivity
Southampton Study Limitations

Undefined time for drink consumption

Time varied between additive intake and
assessment of behavior

Body weight not recorded

Dose could not be adjusted

Behavior assessment data not collected

for the respective placebo phases (weeks
1, 3 and 5)
No easy assessment of intra-individual
variability
 No Proven Causality to
Hyperactivity
Southampton Study Limitations
Observed Effects lack clear statistical
significance
Across both age groups
Across both additive groups (Mix A and Mix B)

Behavior changes only partially significant

Measured in the non-standard global
hyperactivity audit
 No Proven Causality to
Hyperactivity
Southampton Study Limitations
The very weakly statistically significant
effects were only measured under a
constant seven-day treatment period
Would longer exposure exacerbate or eliminate the
subtle effects?
Are the effects transient or persistent?
If the effects are transient, probably not relevant within a human
health discussion.

No biological mechanism for causal association

between the intake of the corresponding additives
and the onset of hyperactivity can be derived
from the results
Stevenson et al., 2011
 No Proven Causality to
Hyperactivity
Southampton Study Limitations
Low mean levels of observed hyperactivity compared to
normal inter-individual variation measured in other studies

Behavioral changes
did not occur in all children in one group
did not occur uniformly across all age groups
not in an even manner for the intake of all additive groups

Slightly amended behavior was observed in all groups given

the additives

But this does not necessarily lead to the conclusion

that the additive mixes caused an increase in
hyperactivity
 No Proven Causality to
Hyperactivity
Southampton Study Limitations
It is simply not possible to draw extensive
conclusions from this study, which is
considered the strongest, most robust thus
far
Extrapolation of the results is not possible
when studying mixtures to each individual
additive, or to other additives
Interpretation/mis-interpretation of this study
suggests the need for standard guidelines
(would be helpful to evaluate conclusions)
 No Proven Causality to
Hyperactivity
Reviews of Southampton Work
European Food Safety Authority (EFSA)
Norwegian Food Safety Authority
German Federal Institute for Risk
Assessment (BfR)
Food Safety Australia/New Zealand
(FSANZ)
Others (e.g., UK Council on Toxicology)
 EFSA Opinion
EFSAs AFC Panel were assisted by experts in behavior, child
psychiatry, allergy and statistics
Conclusions:
study provided limited evidence that the mixtures of additives tested had
a small effect on the activity and attention of some children.
Effects observed were not consistent for the two age groups and for the
two mixtures used in the study.
findings of the McCann et al study could not be used as a basis for
altering the acceptable daily intakes
Noted limitations:
inability to pinpoint which additives may have been responsible for the
effects observed in the children given that mixtures and not individual
additives were tested
 EFSA Opinion
Findings could be relevant for specific individuals showing sensitivity
to food additives in general or to food colours in particular
Not possible to assess how widespread such sensitivity, if present,
would be in the general population (Stevenson et al., 2011)
The significance of the effects on the behaviour of the children was
unclear since it was not known if the small changes in attention and
activity observed would interfere with schoolwork or other
intellectual functioning
The Panel noted that the majority of the previous studies used
children described as hyperactive and these were therefore not
representative of the general population
Norwegian Food Safety Authority
The increase in hyperactivity reported in the
Southampton study after children were challenged with
artificial food colours and sodium benzoate in two
different mixtures (A and B) were considered small
Findings were not consistent between the two age
groups and the two mixtures
Study provides limited support to an increase in
hyperactive behavior from mixtures of artificial food
colors and sodium benzoate
 BfR Expert Opinion
Findings suggest indications of a possible association between the
intake of specific food additives and increased hyperactivity in
children
Observed effects are low compared with normal inter-individual
variation
Behavioral changes do not occur in all children in a group; nor do
they occur in a statistically significant manner in all age and additive
groups.
Trial does not supply any clear evidence of a possible causal
association between additive intake and the observed effects; No
biological mechanism be identified from the findings for a causal
association of this kind.
Additives must be listed on the label of packaged foods. This
means that consumers wishing to avoid any intake of the
additives concerned for precautionary reasons can refrain from
consuming these foods.
 FSANZ opinion
Concluded that there are no public health
and safety concerns due to the results of
the study
No public health and safety risk from the
consumption of foods containing added
colors as part of a balanced diet
 What have other experts said?
Attention Deficit Disorder Association

No research proving that other treatments,

such as neurobiofeedback, nutritional
supplements, hypnosis, visual therapy, or
changes in the diet are effective in
relieving AD/HD symptoms.
 What have other experts said?
CHADD/Natl. Resource Ctr. on ADHD
Dietary treatments eliminate -- or take out
-- one or more foods in someone's diet (for
example, sugar, candy and food with red
dye). The idea is that being sensitive to
certain foods can cause symptoms of
AD/HD. Careful research, however, has not
supported this treatment.

http://www.help4adhd.org/en/treatment/complementary/WWK6S
 Colors: Important Ingredients
Offset color loss due to light, air,
temperature extremes, moisture, and
storage conditions
Natural color in foods fades
Correct natural color variation
Enhance naturally occurring color
Add variety to wholesome and nutritious
foods
 Colors: Important Ingredients
Provide colorful identity to foods that are
otherwise colorless
Add aesthetic appeal
Protect flavors and vitamins that could be
affected by sunlight
Play a critical role in how we taste and
enjoy food (palatability)
Colors: Important Ingredients
A long, safe history of use in food
Society has come to
accept coloring not as
fraudulent, but as a
permissible and useful
signal of food taste
Simply, colors make food
more enjoyable.
Consumer studies shown
consumers will not buy
foods with color variations
from the norm
 Colors: Important Ingredients
Technological limitations to natural colors

Natural colors are great

But, some technological limitations
Stability issues for some natural colors
Limitations in certain applications
Range of colors
Limited resources
 European labeling
In Europe, all food additives are given
labeling codes commonly referred to as
E-numbers
So, colors were traditionally labeled not by
name but by E-number
The EU parliament has now required
labeling for azo-dyes in Europe:
may have effects on activity and attention in
children
 Do US labels need a warning label?

No proven causality to hyperactivity

In the US, FD&C colors are already listed
by name, not by a vague E-number
As with all food ingredients, if consumers
choose to not eat a specific ingredient,
they can see it on the label and make an
informed product choice
 Carmine/Cochineal
US Law: FD&C colors must appear on label
Example: Carmine/cochineal is now labeled
Consumers have the clear knowledge needed to
decide
Consumers can make informed choices
 Colors are important in many applications
Drug dispensing and consumption errors are a
significant health problem
Pharmacists rate color and shape as the most important
attributes for patients to identify medications
Colored tablets significantly reduce medication errors

QuickTime and a
decompressor
are needed to see this picture.
 Why not use natural colors for drug
identification?
In some cases, this works great
But some technological limitations related
to the stability of natural colors
Shelf-life of the active ingredients >1 year
Shelf-life of a natural color may be <1 year
Limited palette of stable natural alternatives
R&D continues
 Summary
Strong and robust dataset supports the
safety of many synthetic colors
No proven causality for hyperactive
behavior
Colors are useful additives that provide
important and beneficial technical effects
Colors are already clearly labeled and this
allows consumers to make informed
choices
Colors are Safe and Beneficial