Prior to the 1950's, the coloring of the nation's food supply was a simple process.   If manufacturers wanted to add color to a food or candy it was done primarily with natural plant and vegetable based compounds.   For example, pale red colors could be achieved from beets - green could be achieved from chlorophyll - yellows and orange could be achieved from extracts from a number of other plants and spices.   However, after WWII, the chemical industry grew rapidly.  In their attempts to increase sales - they saw the food industry as an excellent potential client.

The chemical industry approached the food industry and quickly touted the benefits of artificial petroleum based ingredients in the nation's food supply.  Manufacturing benefits of chemical based colors over natural colors included - convenience, lower cost and an almost unlimited shelve life.  

Regarding safety to consumers, back in the 1950's government over-sight was minimal.  Safety was determined primarily on the amount of a chemical that was needed to kill 50% of the animals, the data was then extrapolated to humans for assessing risk.  Unfortunately, at that time there was no consideration given regarding what is now known as "behavioral toxicology," which includes the potential of a chemical compound to affect behavior, personality and learning ability.  Even today, the FDA and EPA do not require detailed testing of chemicals for subtle effects on these neurological processes.

With the increased public awareness that environmental factors during early life can have profound and enduring consequences, there has also been recognition that even such seemingly benign agents as the artificial colors and dyes widely used to enhance the appearance of foods, drugs and cosmetics may produce dangerous consequences after prolonged use. 

For example, FD & C Red No. 2 dye was previously shown to produce cancerous changes in experimental animals and subsequently removed from general use. While there has been considerable energy expended in searching for carcinogenic potential from artificial colors and flavors, there have been only a few published studies examining the effects of these agents on the behavioral attributes of the developing organism. This is particularly surprising since perhaps the most controversial aspect of the safety of artificial colors and flavors is that relating ingestion of food dyes, preservatives, and artificial flavors to subsequent learning and behavioral problems in children.

Several researchers including Feingold and others, claim that some children show dramatic improvements in attention deficit and hyperactivity behaviors after removing the artificial components from the diet. However, since this original claim, other researchers have set up protocols to test the diet/behavior connection, but without consistent success. However, these unsuccessful projects have been criticized because they removed only one artificial item from the child’s diet, where in actuality, the ADD/Hyperactive child is exposed to many synthetic compounds in his/her daily diet. 

In an attempt to remove greater amount of petroleum based chemicals from the child’s diet, researchers set up a test project in which many types of synthetic petroleum chemicals and known "problem foods" were removed from the diet simultaneously. The results of this experiment were very positive (details outlined below) and provide strong support for the diet/behavior connection.

Further support that artificial flavors and colors can cause behavior problems comes from the experiments of Dr. Levitan, which suggests that xanthane type dyes alter the physiological characteristics of invertebrate neurons and that this biological activity is highly correlated with the lipid (fat) solubility of the dye. In addition, these compounds reversibly inhibit fertilization in some test animals (Carroll, E. J., Journal of Cell Biology, 90: 96a, 1976) and reversibly modify transmission at the frog neuromuscular junction (Augustine, G. J., Neuroscience Abstracts, 2:708, 1976).

The original work by Dr. Feingold in 1970 often claimed 20-50% of children showed significant improvements in behavior following removal of artificial colors, flavors etc. from the child’s diet. Subsequent experiments by other researchers to determine the effectiveness of these claims were rarely as optimistic.. Previous experiments with food dye and behavior in school age children have focused primarily on one type of color at a time. Many of the follow up studies have not shown any definite link with diet and behavior, however a recent study (outlined below) observed major improvements in child behavior when a variety of synthetic and "problem" foods were eliminated from the child’s diet simultaneously

Scientists at the Department of Pediatric Neurology at Yale University found that exposure to a mixture of artificial colors can result in hyperactivity in young rat pups under certain conditions.

Whereas, previous work being done with diet and behavior has focused on school age children, there has been very little investigation to determine if the chemical food additives could alter behavior in the developing organism. To investigate just this question,, Dr. Bennett Shaywitz at Yale University, Department of Pediatric Neurology, set up experiments to determine if low doses of artificial food dyes would alter learning and activity in newborn rat pups.

Unlike other experiments using a single color food dye exposure, the researchers here used a mixture of 5 dyes including blue, green, red, yellow and orange. (This more approximates what a child would receive in the real world on a daily basis.) The food dyes were given to the rat pups beginning at 5 days of age continuing throughout the first month of postnatal life. Amounts given were not in excess, but were calculated to equal the average daily intake for American children (1 mg/kg body weight).

To test the hyperactivity potential, different groups of test animals were given the food color mixture daily for either 12 days, 15 days, 19 days, or 26 days. Activity was counted for 5 minutes for every other 5 minute block during a one hour period . The researchers also created several groups of "attention deficit-hyperactive" test animals by administration of the compound 6-hydroxydopamine (6-OHDA), which has been found to reduce dopamine levels in the brain. This coincides with the theories and observations that ADHD children have altered dopamine levels.

In determining the effects of the "ADD causing chemical" 6-OHDA, it was found that rat pups exposed to the chemical for 12 days showed no difference in activity compared to the non-exposed control group. However, the pups exposed to 6-OHDA for 15 days exhibited activity levels of 66% (actual percentage of time spent moving) compared to 49% for the controls, at 19 days it was 82% compared to 53% and at 26 days it was 70% compared to 50%. Thus, except for the first 12 day period, every time period showed the 6-OHDA exposed animals demonstrated significantly more time in movement. This supports the assumption that lowered brain dopamine levels increases hyperactivity, and therefore suggests other chemicals which alter dopamine levels can contribute to ADD.

The next part of the experiment was to determine how artificial food additives affected the mice. Four different dosages of the food dye were given to each of the above groups, including .0 mg/kg, .5 mg/kg, 1 mg/kg and 2 mg/kg. Although there was not a clear dose response effect of the artificial food color exposure at .0, .5 and 1 mg/kg, the researchers did state, "The high doses (2.0 mg/kg level) produced the greatest increase in activity." This observation was seen in both the rat pups exposed to the 6-OHDA and the pups not exposed to the 6-OHDA.

Learning ability, (in this case called "avoidance learning"), was also weakened in test animals exposed to the food colors. This was determined by observing the animal’s ability to remember their way out of the maze (after learning it once) before a brief shock was administered. Whereas animals not exposed to any colors or 6-OHDA took about 9 seconds to escape the maze, it took over twice as long (23 seconds) for the animals exposed to the lower .5 mg/kg artificial color doses to escape the maze (considered a significant difference). While the other food dye levels also increased escape time by over 30-50%, it was not quite enough to reach statistical significance.

Regarding the observations of hyperactivity after exposure to food dyes, there was enough evidence for the researchers to conclude,

"Our results provide additional support for the belief that administration of food colorings may exert significant effects in the developing organism. Thus, it is apparent that food dyes affect activity levels during the first month of postnatal life."