We are truly concerned about the effectiveness of FDA. Mr. BICKWIT. I have no questions. Thank you very much. Senator HART. And I think I should state on the record our sympathy for our reporter this morning. Some of that testimony involved words which I couldn't understand and I can't imagine how you can spell. So put this on the record in case the home office wonders. We adjourn, to resume in this room at 10 a.m. tomorrow. (Whereupon, at 1:40 p.m., the subcommittee adjourned, to reconvene at 10 a.m. the following day.) FISH INSPECTION LEGISLATION FRIDAY, MAY 21, 1971 U.S. SENATE COMMITTEE ON COMMERCE, SUBCOMMITTEE ON THE ENVIRONMENT, Washington, D.C. The subcommittee met, pursuant to recess, at 10:10 a.m. in room 1318, New Senate Office Building, Hon. Philip A. Hart (chairman of the subcommittee) presiding. Present: Senators Hart, Hatfield, and Stevens. Senator HART. The committee will be in order. Our first witness this morning is the associate professor of medicine at Washington University at St. Louis, Dr. Mitchell Perry. We welcome him. Doctor, your statement, which we appreciate having had in advance, will be printed in the record, so you may proceed if there is any summation or extension. Feel free to proceed. STATEMENT OF DR. MITCHELL PERRY, ASSOCIATE PROFESSOR OF MEDICINE, WASHINGTON UNIVERSITY, ST. LOUIS, MO. Dr. PERRY. What I would like to do is to try to summarize and simplify what I have been told is an excessively complex and technical statement that I submitted. For 40 years cadmium has been known to cause toxic manifestations in man after exposure to really large amounts of the metal, but it has only been recently that the possible dangers of long-term low-level exposure to the metal has been recognized. I would like to emphasize at the outset that such exposure has not been conclusively proven to be harmful, but it is possible that some of the hypertension that occurs in the United States is related to the cadmium that all Americans have accumulated in their kidneys. Since at least 20 million Americans have hypertension and for 80 percent of them the cause is unknown, the subject really does deserve some study. In discussing the problem I would like to consider four topics: (1) Cadmium balance in man; (2) Cadmium toxicity; (3) Some unusual aspects of the biology of cadmium; and (4) Current reasons for suspecting that cadmium may be involved in hypertension. Most foods have less than 50 parts per billion of cadmium in them. That is less than 50 micrograms per kilogram. A microgram is a millionth part of a gram. Thus to eat 50 micrograms of cadmium more than 1 kilogram of ordinary food has to be ingested. There are exceptional foods that are high in cadmium. Such ex 153 ceptional foods include shellfish and the livers and kidneys of domestic animals. The average American intake of cadmium is said to approximate 50 micrograms per day. That is really a pretty soft figure and it may be several times that much. Most of this is in food. There is a little bit in drinking water but probably less than 1 microgram per day, a little bit in inhaled air, but again except in situations of bad contamination less than 1 microgram per day. There is some in cigarette smoke, 2 to 4 micrograms per pack. This means that there are perhaps 50 to 60 micrograms of cadmium that enter the body. Out of this only 2 to 10 percent is absorbed. Once it is absorbed, however, very little of it gets out of the body, that is, is excreted. This means that 2 micrograms or more are accumulated every day and that means that after 30 years, after some 10,000 days, the average American has accumulated some 20 milligrams of cadmium. Half of this is deposited in his kidneys, a quarter of it in his liver. Cadmium absorption from food probably represents a very significant variable and there are two reasons for this. One is that foods vary considerably as do their cadmium content. The other is that the percentage absorption of ingested cadmium probably can vary considerably. Under unusual circumstances, specifically when calcium or when protein is low in the diet, a lot more cadmium than usual-10 percent instead of 2 percent-can be absorbed. CADMIUM TOXICITY There are three types of poisoning from unusually heavy exposure to cadmium that are recognized. Large industrial exposures have resulted in emphysema when the metal was inhaled and kidney damage when it was ingested. In addition, there is an actual disease apparently associated with massive environmental poisoning in Japan known as itai-itai. To get this in perspective, kidney and liver in massive poisoning of 100 to 200 milligrams of cadmium per kilogram of tissue. This is three to six times what is found in the ordinary, normal American adult. In addition to these obvious poisonings from large amounts of cadmium, there is an intriguing and very important problem of the significance of the ordinary, smaller intakes of cadmium. These result in the impressive accumulations of renal cadmium found in the general population, that is, in people with no particular exposure to cadmium. Five toxic effects of cadmium have been suggested: Cancer of the prostate, testicular damage, anemia, emphysema, and hypertension. There simply are not enough data to discuss the first three meaningfully. What that means is that nobody has really looked at this. We just do not have the information. The possible relationship of emphysema to ordinary environmental cadmium is not appropriately discussed here since in this situation the metal is presumably inhaled, not ingested. This leaves only the possible relationship of hypertension to cadmium, a subject I want to discuss. But before I do I would like to comment about the unusual aspects of the biology of cadmium, and there are several of these. There are some 18 chemical elements which have specific biologic function in living tissue. These are designated "essential elements." Many other elements are currently designated nonessential because they are not now known to be required for any biologic function. Yet they are constantly present in small but measurable concentrations. Cadmium is one of these. Cadmium differs from the other nonessential elements in several important ways: (1) It is strikingly concentrated in one tissue, the kidney. (2) Its concentration is very low in the newborn baby and it accumulates with age. (3) There are marked differences in kidney cadmium, depending on an individual's geographic origin. (4) Finally, cadmium in the body is bound to an unusual protein which binds both cadmium and zinc. A word about each of these, First, the distribution of cadmium is certainly unique. Its concentration in the kidney is more than 10 times its concentration in the liver and that in turn is at least several times its concentration in other organs. Second, concentrations of renal cadmium vary with the geographic origin of the subject. White subjects from the United States, Switzerland, and India have more cadmium than black subjects from Africa, but they have less cadmium than Mongoloid subjects from Asia. At present the World Health Organization is involved in extending these preliminary observations and in more precisely mapping the geographical differences in kidney cadmium. It is their hope to correlate their results with blood pressures in these people. Third, little cadmium is present in the newborn-only about a tenth of a percent of the adult concentration. Thus the metal accumulates during an individual's whole life, particularly during the first two decades. Finally, the chemical form of kidney cadmium is very unusual. It is combined with a particular protein which at the moment has no known function. THE POSSIBLE RELATIONSHIP OF CADMIUM TO HYPERTENSION What is the real significance of this renal cadmium? Is it merely an inert contaminant in the human body or does it have some subtle but significant effect even in concentrations well below those where it produces the unequivocal toxic effects that I mentioned previously? The answer to this question simply is not known, but there is some season to wonder whether average concentrations of cadmium might increase blood pressure and so be responsible for some part of human hypertension. It must be reemphasized that there is no proof of this, but such a relationship has been suspected on the basis of several observations. The most important of these is that chronically fed cadmium induces hypertension in rats and the kidney cadmium concentration of such rats approximates that which is found in the average American adult. In 1962 hypertension was observed in rats following long-term cadmium feeding. From the time of weaning these rats received a diet containing 5 parts per million of cadmium. At 17 months—and that is about half a lifetime for a rat-half of the cadmium-fed animals were hypertensive. At 30 months two-thirds of the cadmium-fed animals had become hypertensive, although by that time one-eighth of the untreated rats had also become hypertensive. The difference between the two groups, however, was still highly statistically significant. Recently we have observed an early but significant elevation in the blood pressure of rats given from 212 to 25 parts per million of cadmium in their drinking water for 6 months. Our experiments are still early and we are just beginning to see hypertension, but it looks as though as little as 212 parts per million of cadmium may cause difficulty. The story really has to be left at this point incomplete and uncertain of significance, but it seems very likely that hypertension occurs in animals following long-term ingestion of cadmium. The significance of such cadmium-induced increases in blood pressure and their relationship, if any, to essential human hypertension will probably not be known until we have much more information about the mechanism of the animal hypertension and more information on the biologic effects of accumulated cadmium in man. At present the most disturbing fact from the point of view of establishing such a relationship is the failure to observe hypertension in patients with known industrial exposure to cadmium or with itai-itai. Although this requires explanation, it is not necessarily fatal to the hypothesis since animals exposed to excessive doses have become sick but not hypertensive. At present there is no conclusive evidence that cadmium accumulation resulting from long term, low-level exposure is harmful, but I think that there is enough suspicion to warrant an attempt to limit the cadmium exposure of the American people. Thank you. Senator HART. Thank you, Doctor. I get the feeling as we learn more and more from experts that all of us will be on peanut butter until they discover something wrong with that. This is not to discount in the least your caution but I suppose just to voice the wonder that many people are, I suspect, voicing about when we will reach the day when we are cautioned to eat nothing. You are saying that cadmium, ingested, would possibly cause hypertension in a human being. Let me see if I can paraphrase what you are really saying. You are saying that you base that conclusion on data which, among other things, showed hypertension in rats with cadmium levels in their kidneys similar to levels which are currently found in the average human body. Dr. PERRY. That is correct. Senator HART. I suppose all of us ought to be watching the levels of cadmium-containing foods that we take in. Everybody would agree on that based on your statement. Do we know what foods do contain these excessive amounts of cadmium? |