The presence of toxic substances from the environment that find their way into the food chain and, eventually, into infants and children has implications for both present and future health. Some perspective is necessary to understand the scope and severity of the threat.
We need first to define toxicity. Everything may be toxic - including water, salt, and oxygen - when in high enough doses or at the wrong time. We shall here be concerned with small dose toxicities but must remember that there will be striking differences depending on whether a toxin is cumulative. Cyanide, found in many foods (e.g., lima beans), is highly toxic in small doses but in microdosage becomes harmless because of rapid excretion.
Thus, not only dose but metabolic fate and rate are very important. The effect over time for such subtle biologic processes as mutagenesis and oncogenesis also becomes as important, but to assess such properties in human beings takes decades or even generations. For these concerns we expect to have more questions than answers.
In approaching the topic as applied to infants, we shall have to bear in mind transplacental effects, the presence of the substances in milks (human and others) and, finally, other dietary items. In historical order we shall look first at naturally occurring toxins, then at substances deliberately added by the food industry to see which if any are suspect, and finally at substances added to the environment for reasons unrelated to food preservation that have contaminated the food supply.
The "natural" toxins include those that come from decay or microbial action and chemical substances needed and incorporated by forms of plant life but not safe for animals. The decay and microbial degradation represent the basis for using, in the first place, many of the food additives to be discussed in the next section. The various food poisonings from bacteria and bacterial toxins are well known and need no further emphasis here. Fish muscle of the scombroid group develops oxidative poisoning on standing; fish caught on reefs (snapper, yellowjack, and others) may be infected by algae, which elaborate a nasty neurotoxin (ciguatera poisoning). Children, being smaller, are more severely affected by these toxins than adults ingesting the same amount. Nitrates that may react with amino acids to form nitrosamines are found naturally in broccoli, spinach, and lettuce in concentrations as large as the nitrate concentrations now under discussion for banning in meat preservation. Nitrosamines are carcinogenic in several animal species. Their role in human health is undefined. Natural substances thus require our attention just as do "unnatural" ones.
The additives placed in foods by the industry have had considerable scrutiny of late. As already pointed out, one role for these is preservation. Here the trade-off has to be measured with care lest we revive some old diseases in high incidence in place of the newer ones we might prevent by withholding a preservative. On the other hand, things added for color or flavor have less redeeming value and should not have equivalent standing. The list of additives is too long for detailed discussion here; suffice it to say that the recent concern has helped improve vigilance in this field.
The most common additive is sucrose, dangerous only in that it supplies energy without other nutrients, thereby diluting the per-calorie amount for each of the other primary sources of energy, protein and fat. This can be good as when adding sugar to evaporated milk mixtures (at home or in the infant-food industry) to give optimal balance to the feeding, especially for renal-solute load. It can be bad when so much carbohydrate is added that the per cent of calories from protein falls below the critical minimum or when some other nutrient (e.g., phosphorus) falls below that needed per calorie. Salt may be deleterious by increasing the solute load (protein supplements can also produce this evil), or salt can be so severely restricted that metabolic alkalosis or hypovolemia results.
These last phenomena are likely only when a single food, such as an infant-formula milk substitute (e.g., soybeans), is the sole source of nutrition. On mixed diets, such deprivation is most unlikely. Relatively high salt ingestion over years as a cause of hypertension in later life has been suggested by animal studies. If so, only some individuals would presumably be affected rather than all. Little applicable knowledge is at hand. For a very small number of persons, even human milk may be toxic (galactosemia).
Artificial sweeteners, such as cyclamates and saccharin, which have low-level oncogenicity (animal and epidemiologic studies), may be a special problem for children - whose life expectancy is obviously greater, so that more time for expression exists. People of good will differ on the social trade-off here, but prudence would seem to dictate avoidance of these substances, since no real benefit accrues.
Finally, the most important group of compounds for our consideration - the contaminants of the environment placed there by man. Among these are organic mercurials, a long list of pesticides, and the polyhalogenated phenolic compounds used in industry. This whole group has in common the potential for transplacental transfer, appearance in breast milk, and storage in lipid depots. All are fat-soluble, accounting for those properties.
Mercury at first seems out of place in this company. Metallic mercury is not very toxic until it becomes an inorganic salt or becomes either acylated or arylated. The element is placed into the modern environment either by industry - chiefly paper mills discharging an effluent - or its use as a fungicide on seed grain. Either way, such organic compounds as methyl mercury are produced by bacterial action. When this occurs in waterways, the methyl mercury is picked up by plankton, then successively by larger aquatic animals, and ultimately by the largest species of fish. Storage in fat places the largest amount in the largest fish.
A similar food-chain route is followed by the other lipid-soluble compounds. When seed grain is the source, some misadventure has occurred - e.g., the grain was fed to farm animals or, as in the terrible disaster in Iraq, to human beings instead of being planted. When the amount is large, the toxicity to the ingesting animal is primary. In other instances, the fact that the material is well stored leads to the recipient at the top of the food chain as the one eventually poisoned.
There are basically only two ways a nonmetabolized lipid-soluble substance may be removed from a mammal. Both are female routes. The molecule may cross the placenta to the fetus, or the compound may appear in the animal's milk. In the clinical disasters that have occurred and have been studied, when such substances have wreaked their havoc, about half the dosage for affected infants came transplacentally and half via breast-feeding.
Methyl mercury is a severe toxin that affects the CNS, among other tissues. When a sublethal amount is ingested, permanent brain damage is a possible sequela. Clearly, an infant born to an intoxicated mother should not be breast-fed.
Pesticides, including DDT, dieldrin, and others, also have found their way into human lipid tissue, have crossed placentas, and appear regularly in the milk of women in developed countries. Because animal fat is a significant dietary source for human beings, human milk has more of these compounds than cow's milk obtained from grazing animals. Some pesticides, however, do appear in cow's milk. In the contamination detected to date, no human illness has been traced to these compounds when they were acquired through the food chain. Since they are potent agents, known to be toxic in higher doses, and oncogenic in experimental animals, continued surveillance for many years (generations?) will be needed before the impact will be finally known.
Industrial wastes other than mercury that are lipid-soluble have also entered the food chain and are now found in animal and human fat. The best known of these are the polyhalogenated biphenyls. The chlorinated members of the group, or PCBs, were and still are used industrially as heat exchangers. The principal use has been in the manufacture of heavy electrical equipment. These compounds also have in the past been incorporated into hydraulic fluids and employed in a number of other applications. Unfortunately, from the time of their introduction, in the 1930s, until a few years go, there was a rather permissive attitude about discharging apparently nontoxic (also nontested!) material into effluents that entered rivers and lakes. PCBs entered bacteria, algae, plankton, and, eventually, small fish, large fish, and man (presumably, bear as well). Most PCBs are not very metabolically active, and they sit in adipose tissue for years or, possibly, decades. Some regions of the country have had heavier contamination than others; the Hudson River and some of the Great Lakes are such areas.
Three alarms have been sounded. First, some PCBs (they vary according to the number of chlorine atoms - from one to 10) are mutagenic and oncogenic in experimental animals. Second, an accident occurred in Japan wherein PCBs contaminated, in high concentration, a supply of rice oil. The ingesters of this oil, a whole village of people, became ill. Pregnant women in the exposed group had increased fetal wastage, and some delivered babies with a brown ("colacolored") discoloration of the skin and other evidence of illness. The affected infants who were breast-fed became more ill.1 Some of these infants had developmental delay.2 Finally, the experimental reproduction of this accident in monkeys has demonstrated the same findings, including wellestablished evidence of CNS injury to the affected monkeys.3,4
The brominated biphenyls (PBBs) compounds used as fire retardants entered the food chain in a spectacular accident in the state of Michigan in 1973.5 Through error, PBB was substituted for magnesium oxide in winter cattle fodder for much of the cattle in the state. From there it went into the cows, their milk, and - since the same food was fed to other farm animals - chickens and eggs, sheep, hogs, pets, and, through consumption of some of these, the people of Michigan.
Some of the cattle were sick, and there were some fatalities among the dairy herds. Whether any definable clinical human illness has occurred remains controversial. Studies are in progress but will take many years to complete. This is especially true for children. There is no question that many thousands were exposed and that certain farm families had much higher exposure than the others. Because PBBs are chemically and biologically similar to the PCBs, the same sort of information, the same gaps in knowledge, and the same concerns apply.
The Committee on Environmental Hazards of the Academy of Pediatrics has taken as two of its responsibilities a watchdog role for monitoring problems of contamination of the food chain and an educational role for pediatricians and the public. We have also urged government activity in monitoring and, even more important, government funding for anticipatory research in this whole field of the effects of environmental chemical contamination of the food chain on the health of the fetus and of children. The implications for breast-feeding are also a part of this challenging modern problem.
It is paradoxic that as we conquer the ancient problems of famine, inadequate shelter, and disease through science and technology, we also create new diseases and new problems. Physicians must keep pace and pediatricians must emphasize those diseases affecting fetus, infant, and children - including effects that may not be manifest until adult life.
1. Kuratsune, M., Yoshimura, T., Matsuzaka, ]., and Yamaguchi, A. Epidemiologic study on Yusho, a poisoning caused by ingestion of rice oil contaminated with a commercial brand oí polychlorinated biphenyls. Environ. Health Perspect. 1 (1972), 119.
2. Herada, M. Intrauterine poisoning: clinical and epidemiological studies and significance of the problem. Bull. Inst. Constitutional Med. Kumamoto Univ. 25 (Suppl.) (1976), 1.
3. Allen, J. R., and Norbach, D. H. Radiobiological responses of primates to polychlorinated biphenyl exposure. Natl. Conf. Polychlorinated Biphenyls. EPA-560/6- 75-004, EPA, Washington, D.C., pp. 43-49.
4. Miller, R. W. Pollutants in breast milk. J. Pediatr. 90 (1977), 510.
5. Finberg, L. PBBs: the ladies' milk is not for burning. J. Pediatr. 90 (1977), 511.