ANNEX 8 



Potential Health Hazards of Mercury in Fish 



by 



Albert C. Kolbye 



Deputy Director, Bureau of Foods 



and 



Acting Director, Office of Science, 



Food and Drug Administration 



Washington, DC 



At the outset, I should like to emphasize several points that I would like 

 you to keep in mind throughout my presentation. I will be talking initially 

 about the effects on health caused by excessive exposures to methyl mercury. 

 In the normal course of events there is very little, if any, likelihood that peo- 

 ple living in the United States would receive exposures comparable to the 

 Japanese villagers later described. However, it is necessary to describe what 

 can occur in the extreme if we are to understand the present perspective on 

 mercury as a potential health problem in the United States and why the FDA 

 has set a guideline for mercury in fish. 



There is no reason for public alarm or distortion of risk by magnification 

 beyond the true perspective, because no health crisis is imminent from mer- 

 cury in fish. We should understand, however, that there is reason to exercise 

 prudence and caution, hence the existence of the FDA guideline. Towards the 

 end of my talk I will go into the guideline itself and explain some of the 

 reasoning behind it. I would also like to emphasize that there has been no ful- 

 ly documented instance of a U.S. resident suffering clinically evident mer- 

 cury poisoning from exposures to mercury in fish. However, the occasional 

 presence of subclinical brain damage from excessive exposures to mercury in 

 fish has not been excluded, particularly in relation to children of mothers who 

 eat unusually high amounts of fish containing substantial amounts of mer- 

 cury in the form of methylmercury. One reason for the guideline is to protect 

 pregnant women from inadvertently damaging their unborn children. 



The potential health hazards of excessive exposures to mercury in fish 

 primarily relate to the particularly toxic form of mercury most frequently en- 

 countered in both freshwater and pelagic fish. Methylmercury is the par- 

 ticularly toxic organic form which, because of its biochemical characteristics, 

 is almost totally absorbed from the human gastrointestinal tract and cir- 

 culated through the blood to the various organs and tissues where a range of 

 harmful effects can potentially occur. In contradistinction to either inorganic 

 or other organic forms of mercury when ingested, methylmercury can more 

 readily penetrate the "blood-brain barrier," enter the brain tissue, and cause 

 irreversible damage to brain cells. If methylmercury were easily and quickly 

 excreted from the human body, then occasional exposures to foods containing 

 higher than normal background levels of methylmercury would present little 

 reason for public health concern. However, such is not the case with 

 methylmercury. 



When we speak of the biological half-life of a substance, we refer to that 

 period of time necessary before the body can rid itself of 50Tc of the initial 

 amount present. The biological half-life of methylmercury in humans has 

 been determined by observational studies on exposed humans and by direct 

 experimentation on human volunteers with orally administered radioactively 

 labeled methylmercury. The observational results indicate that 69-70 days 

 and 76-83 days represent the biological half-life for red blood cells and 

 plasma, respectively, after ingestion of fish contaminated with methylmer- 

 cury. The biological half-life of methyl mercury -203 as determined by total 

 body measurement of the volunteers was 70-74 days. 



Why should we be concerned with this biological half-life of 70 days? The 

 practical significance relates to the problem of accumulation in the body if 

 intake exposures are significantly greater than excretion. Please note that 

 various organs such as brain tissue may have a longer half-life than 70 days, 

 while other tissues may have a shorter half-life, thus resulting in the average 

 net half-life of 70 days. Our primary concern is with accumulation of 

 methylmercury in the brain and at this point I should stress not only the 

 adult human brain but more importantly the developing fetal brain. 

 Methylmercury easily crosses the human placenta into the blood of the 

 human embryo as it develops in utero. As the human embryo goes through 

 the various stages of development before birth of the infant, its developing 

 tissues are much more sensitive to damage from toxic substances than are 

 adults. This is especially true for fetal brain tissue which can be exquisitely 

 sensitive by comparison. 



Accumulation of methylmercury in the human body has been documented 

 many times as to the occurrence of the phenomenon and the brain damage it 

 has caused in humans unfortunately exposed to highly contaminated foods. 

 Additionally, we have other information from accidents and industrial ex- 

 posures of pesticide workers. The results of experimental exposures of test 

 animals, including monkeys, corroborate the cause-effect relationships of 

 methylmercury to brain damage in human adults and infants. I will try to 

 summarize the most significant points of information for you. 



Two episodes occurred in Japan involving fairly large numbers of people 

 and the opportunity to perform in-depth studies. The villages of Minimata 

 and Niigata suffered similar problems during the 1950's and early 1960's. 

 Fish and shellfish in the areas contained high levels of mercury (almost en- 

 tirely in the form of methylmercury) resulting from local pollution by in- 

 dustrial sources. As you know, the Japanese consume more seafood in their 

 average diet than we do. There were 121 cases of human methylmercury 

 poisoning reported in Minimata of whom 46 died. Among the 121 patients, 

 there were 23 infants and children who were affected with a severe cerebral 

 palsy-like disease from 1954 to 1959. The important thing to remember here 

 is that none of these infants and children so affected had consumed any of the 

 contaminated seafood themselves. Most were bom with the affliction not 

 only being clinically obvious but in many cases, severe. Some of the severely 

 afflicted have never seen, heard, spoken, or made a purposeful motion in 

 their lives and in the figurative sense they exist as human vegetables. Others 

 are less affected but still severely handicapped. Now comes the 

 "hooker" — their mothers appeared to be normal. There were no clinically ob- 

 vious signs of poisoning among the mothers at that time, yet their bodies had 

 acted to accumulate methylmercury which was transferred through the 

 placenta to their own children while the children were developing embryos in 

 the womb. 



An additional 47 people, 6 of whom died, were reported from the Niigata 

 episode. I visited Japan in 1971 to perform a follow-up evaluation on the 

 Minimata villagers and learned that more cases have been recognized than 

 had been reported earlier, apparently due to the delayed effects of 

 methylmercury poisoning not being recognized earlier in some of these 

 patients. One case was of particular interest. It involved a physician who ob- 

 viously would be more likely to recognize the early symptoms of mercury 

 poisoning which include tremor, nervousness, and impairment of both vision 

 and coordination. He celebrated one evening and drank too much. Instead of 

 waking up with a hangover, he awoke the next morning with clinically ob- 

 vious symptoms of mercury poisoning and died 10 days later from the disease. 

 At autopsy, his brain showed advanced tissue damage with all the typical 

 brain tissue pathologic findings of mercury poisoning. Apparently, he had 

 been able to compensate partially for the damage in brain function. Since the 

 onset of the disease in adults can be gradual he was able to compensate 

 enough to live a fairly normal life until additional brain damage from high 

 alcohol consumption tilted the delicate balance of compensation and his 

 brain could no longer function well enough. 



Similar advanced brain damage has been noted to result in Scandinavia 

 after accidental short-term industrial exposure to alkyl mercuric pesticides in 

 which the worker involved died 20 yr later from an unrelated cause without 

 additional mercury exposures. There have been other unfortunate human ex- 

 periences with methylmercury poisoning dating as far back as the original 

 laboratory workers who first synthesized the compound and as recently as the 

 current massive poisoning outbreak in Iraq due to the wrongful diversion of 

 methylmercury treated seed wheat by farmers into bread. 



The ability to compensate partially for damaged brain tissue has also been 

 noted in Swedish studies of monkeys experimentally exposed to methylmer- 

 cury. Some of the monkeys apparently were largely unaffected as far as their 

 normal patterns of brain function were concerned, while others showed gross 

 deterioration of brain function much earlier during the course of the experi- 

 ment even though the exposures to doses of methylmercury were similar. 

 Generally speaking, however, once a monkey showed signs of brain damage, 

 further deterioration was very rapid with death usually following shortly. 

 When some monkeys showed signs of advanced damage, the Swedish in- 

 vestigators then sacrificed several other monkeys apparently unaffected by 

 similar exposures to methylmercury and found extensive brain damage at 

 autopsy. Also, when monkeys apparently unaffected were allowed to live 

 longer, symptoms then occurred with unpredictable sudden rapidity and a 

 quick demise. Similar findings have been noted when cats and rats were 

 studied. These were all adult animals. 



There are several points that these findings bring to our attention. Severe 

 brain damage from excessive exposures to methylmercury may go undetected 

 in some adults for a while but the damage has occurred even though the time 

 of onset of clinically obvious symptoms may vary with the particular in- 

 dividual. The brain damage is irreversible although partial compensation 

 may temporarily delay onset of obvious disease. Excessive exposure to 

 methylmercury may also contribute to early demise of brain function without 



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