UNIVERSITY OF CALIFORNIA
ENVIRONMENTAL TOXICOLOGY NEWSLETTER
Vol. 9 No. 2 May 1989
FOOD SAFETY ISSUES II.
Table of Contents Page No.
II. NRDC Report and Alar
III. State Specific Estimates of Smoking-Attributable Mortality and Years of Potential Life Lost -- United States, 1985
IV. Smoking-Attributable Mortality, Morbidity, and Economic Costs -- California, 1985
V. Scombroid Fish Poisoning -- Illinois, South Carolina
VI. Vet Tox Notes: Legal Source of Methylene Blue
VII. Review of Federal Pesticide Proposal
The lead article in this issue of the Environmental Toxicology Newsletter is an article that many of you have already seen. The Alar issue and the release of the NRDC Report "Intolerable Risk: Pesticides in Our Children's Food", set off a food safety scare in this country which was incredible. Response to the issue has taken literally weeks of time on the part of many UC employees, and hundreds of state and federal employees (it would be interesting to know just how much was spent to address the "food safety crisis"). In actuality there was no sudden "crisis" or threat to us; it was a perceptual problem. It is likely that much more money (public and private) will be spent on residue testing so that consumers may perceive greater safety and have renewed confidence in the food supply.
From a public health perspective, it is a real shame that limited resources (human and monetary) will be redirected towards a perceived health problem when there are serious actual problems such as alcohol and drug abuse (including tobacco) where these resources could have a measurable beneficial effect.
The rest of the newsletter contains two excerpted articles on smoking, a couple of announcements, and an update on a senate bill which will be of interest to most readers.
II.NRDC Report and Alar
The National Resources Defense Council (NRDC) recently issued a report claiming that American children are facing a "massive public health problem" due to the presence of pesticide residues in their foods. In their report entitled "Intolerable Risk:
Pesticides in our Children's Food", the NRDC estimated that as many as one child out of every 3500 in this country may eventually develop cancer solely as a result of their exposure to eight pesticides or pesticide metabolites found in fruits and vegetables. Ninety percent of the estimated risk was alleged to occur solely from the presence of residues of the pesticide Alar (chemical name - daminozide) and its breakdown product UDMH in apple products.
The report has generated considerable media attention and public response. Public outcry from the findings and publicity surrounding the report have led several major school districts, including those in New York City, Los Angeles, and San Francisco, to temporarily eliminate all apple products from school food programs until residue test results are available.
The conclusions of the NRDC study have been soundly criticized as misleading by several scientists throughout the country and the validity of the procedures used by the NRDC to estimate cancer risks has been questioned. The NRDC's estimation of the cancer potency of UDMH, which was cited as being the primary cause of cancer in the study, was based upon data that were rejected in 1985 by an independent Scientific Advisory Panel established by Congress to provide scientific peer review of pesticide actions by the U. S. Environmental Protection Agency (EPA). The NRDC risk calculations also relied upon questionable food-consumption data that were based upon a small survey that had a relatively poor participation rate. As a result of these limitations in the NRDC study, the EPA recently concluded that "the practice of using data rejected by scientific peer review, coupled with food consumption data of unproven validity to calculate 'risk estimates' is misleading. NRDC's estimates of risk posed by pesticide residues in food are far out of line with existing data. These factors plus other differences in procedures used by EPA and NRDC to estimate exposures to risk account for a 100-fold difference in the estimated risk that Alar poses for children and also for 90 percent of the total cancer risk to children claimed by NRDC."
While refuting the claims of the NRDC report, the EPA acknowledges that it is still concerned about the dietary risks of Alar and plans to take action to remove the chemical from the marketplace. In the meantime, the EPA considers risks acceptable since exposure is limited. EPA calculations estimate that the risk of cancer from lifetime exposure (70 years) to Alar is 45 persons per one million and that the estimate of risk to children during the eighteen months it would take to remove the chemical from the market is nine per one million.
According to EPA, "in regard to cancer risks, EPA's stated policy is that lifetime dietary cancer risks generally should not be greater than one cancer per million persons exposed. This is the reference point for 'negligible ' usually used by EPA (and other government agencies). For example, EPA recently cancelled 42 uses of the pesticide captan and retained 24 uses after determining that all food uses of captan may pose risks of cancer greater than a negligible risk. By cancelling some uses, the remaining uses pose risks within an acceptable range. It is important to understand that risk estimates based on animal testing are fairly rough estimates and do not accurately predict human disease. For example, EPA risk estimates mean that there is a 95 percent certainty that the risk is no higher than that estimated by the agency. It may be lower and may even be zero."
Alar was registered by the EPA in 1963 as a systemic plant growth regulator. It is used primarily on red apples intended for the fresh market and is not used significantly on apples destined for processing (apple juice, applesauce, etc.). At the present time, the EPA estimates that only about four percent of the U.S. fresh market apples are treated with Alar, which is down from 25 percent in 1986.
Alar is used to promote uniform-size fruit and fruit firmness. Treatment of apples with Alar reduces fruit bruising during shipping and handling and increases storage life by two to three months. It also delays fruit ripening and premature drop which allows for harvesting to be conducted at a single time rather than over a period of up to six weeks. By delaying fruit ripening, Alar promotes increased red color in apples with no advance in maturity or reduction in quality.
Recent residue findings indicate that the levels of Alar and UDMH in apple products at the time they are sold are typically quite low. Preliminary results from residue tests conducted in Los Angeles have indicated no detectable Alar or UDMH residues from apple products removed from school district food programs.
The National Food Processors Association (NFPA) reported that of the 21,000 apple products analyzed for Alar in 1987-88, 98.3 percent did not contain any detectable residues while the remaining 1.7 percent contained residues far below the allowable tolerance level of 20 parts per million. In greater than 99 percent of baby apple juice samples, no Alar was detected.
These results are in apparent contradiction with those reported on a recent '60 Minutes' television program by the Consumers Union which detected Alar in roughly two-thirds of 32 samples. In all cases where Alar was detected, however, the levels were below one-half of one part per million. The detection limit in the NFPA analysis was one part per million, which explains the differences in the findings. Detection limits in the Los Angeles studies are not available. Market basket surveys have indicated that levels of Alar's breakdown product, UDMH, when detected, are typically between one and three parts per billion on fresh apples. The levels of UDMH in applesauce and apple juice increase to 15 to 30 parts per billion as a result of heat treatment during processing. Washing apples is not effective in reducing residue levels.
Although Alar was labeled as the "most potent carcinogen in the food supply" by an NRDC representative during the '60 Minutes' segment, its status as a carcinogen is questionable. A report from a 1984 study indicated that Alar caused an increase in blood vessel tumors in mice at the highest dose tested. After review of the study by the EPA's Scientific Advisory Panel, it was concluded that the study was flawed and invalid since a high incidence of blood vessel tumors was also observed in control animals that were not exposed to Alar. An additional Alar carcinogenicity study has recently been completed in mice and rats at four different dose levels for male and female animals (16 total cancer assays) and it was concluded by the EPA that Alar was not carcinogenic in any of the assays. Additionally, mutagenicity tests in five different types of assays indicated that Alar was not mutagenic.
Studies investigating the carcinogenicity of UDMH have been in progress for the past year. The midterm assessment of the studies did not reveal any increase in tumors in rats (male and female) given 1, 50, and 100 parts per million of UDMH in their drinking water, or in male mice given 1, 5, and 10 parts per million in their food, or female mice given 1, 5, and 20 parts per million in their food. Final conclusions cannot be made until completion of the studies. After the studies were initiated, the EPA requested that additional tests in mice be performed at 40 and 80 parts per million. The midterm (one year) assessment of the animals receiving 40 parts per million revealed no increase in tumors. In mice dosed with 80 parts per million in their total diet of UDMH, dramatic toxic effects were noted, including 1) death of many animals in the study (80 percent in less than 72 weeks), 2) severe darkening of the liver, and 3) an increase in the number of tumors. It is apparent that this high dose level exceeds the Maximum Tolerated Dose (MTD) which is typically thought to be the maximum dose that will not cause more than a 20 percent decrease in the rate of weight gain of the animals. In carcinogenicity studies where the MTD is exceeded, the test results are typically considered invalid. At any rate, final evaluation of the test results will be made at the conclusion of the study.
In terms of food safety, the U. S. Food and Drug Administration considers pesticide residues in foods as only its fifth food safety priority, and far less of a concern than 1) microbial contamination of foods (i.e. bacteria, fungi in foods cause several deaths each year and lead to millions of dollars in medical costs and significant decreases in human productivity), 2) nutritional imbalance (eating a balanced and varied diet complete with fresh fruits and vegetables decreases risks of certain types of cancer and heart disease), 3) environmental contaminants such as lead and mercury, and 4) naturally-occurring toxins.
An excellent perspective on the importance of pesticide residues in produce is offered in a recent report from the National Academy of Sciences (NAS). The NAS report was based on three years of consideration of data on the relationship between diet and disease. One of the NAS recommendations was that people should eat more fruits and vegetables; the NAS did consider this recommendation in light of potential risks associated with ingesting pesticide residues on produce. Two portions of the NAS report are reproduced below:
"Increased consumption of vegetables and fruits can be expected to result in increased ingestion of residues of herbicides and pesticides used in agriculture. Therefore, the committee emphasizes the need to wash all raw fruits and vegetables thoroughly." *
"Furthermore, the potential small increased risk of these somewhat uncommon tumors that might result from increased exposures in the general population would be greatly outweighed by the potential benefits (i.e. reduced risk of cancers of the lung, stomach, colorectum, and other sites and reduced risk of other chronic diseases) to be expected from greater fruit and vegetable consumption. Thus, the committee concluded that the recommendation to consume liberal amounts of fruit and vegetables is appropriate and poses no undue competing risk."
From the NAS report, we can make a statement that the hazards from not eating fruits and vegetables because of fear about the effects of pesticide residues would far exceed the potential dangers posed by ingesting the residues. The NAS dietary studies were done using human data and thus can be applied directly to other human populations. The health effects were measured in human populations and we can make reliable predictions about how diet will effect future human health.
The potential human health effects from ingesting pesticide residues can only be predicted using animal data and should be done only when the data are valid. Such risk assessments are useful from a regulatory perspective. It is not valid to use such estimations to predict actual human "body counts". Using laboratory animal data in human health risk assessments is necessary and it introduces uncertainty into the procedure. The numbers usually presented to the public about the risk of chemical exposure are the highest (upper bound) estimates, meaning the highest incidence that we would expect based on the mathematical risk assessment model. The lowest (lower bound) estimate is usually 100 to one million times lower; it is often zero. The actual risk will never be known because it is not possible to accurately measure such small changes (one in a million, or even one in a thousand) in the incidence of major human diseases in human populations. (The incidence of human cancer from all causes is about one in four.)
Based on careful consideration of the data we have in hand, we encourage people to follow the recommendations of the NAS committee and to continue to eat fruits and vegetables, including apples.
*We recently received information that the United States Department of Agriculture (USDA) does not recommend using soap to wash fruits and vegetables, and that the FDA concurs. The FDA states that detergents (such as those used for dishwashing) have not been tested for safety of consumption.
Jointly authored by Carl Winter, Art Craigmill and Mike Stimmann
Once again, it's time for a reminder (two of them actually) that the most dangerous chemicals to human health and which can still be purchased at supermarkets, are contained in tobacco products. The second article in this double-barreled blast, gives an indication of the extent of the dollar costs to our state each year.
III.State-Specific Estimates of Smoking-Attributable Mortality and Years of Potential Life Lost -- United States, 1985
Cigarette Smoking is the chief avoidable cause of death in the United States. Although annual estimates of smoking-attributable mortality in the United States vary by method and data source, the estimates are uniformly large and range from a low of 270,000 to a high of 485,000. An estimated 320,515 deaths were attributable to smoking in 1984, representing approximately 16% of the total deaths in the United States for that year. Years of potential life lost (YPLL) have also been used to measure the impact of smoking-attributable disease.
For smoking-attributable deaths and YPLL, the smoking- attributable fractions (SAFs) for 21 smoking-related diseases among adults were calculated using weighted relative risks estimated from four prospective studies on the health effects of smoking. In addition, risks for four pediatric diseases related to maternal smoking were included in the SAMMEC (a computer software program) calculations. The smoking-attributable YPLL were calculated by two methods: 1) to age 65 years and 2) to average life expectancy. State-specific rates per 100,000 persons for smoking-attributable mortality and YPLL were calculated using state-specific population data provided by the U.S. Bureau of the Census for 1985.
According to state-specific estimates, more than 314,000 U.S. deaths were caused by smoking in 1985. The average number of smoking-attributable deaths per state was 6168 (ranging from 271 in Alaska to 28,533 in California). Of all smoking-attributable deaths in the United States, 67% were among men, 32% among women, and <1% among children <5 years of age. These deaths in young children resulted from low birthweight/short gestation, respiratory distress syndrome, other respiratory diseases of the newborn, and other diseases of children associated with maternal smoking. Smoking-attributable deaths accounted for approximately 936,000 YPLL before age 65 years in 1985. When average life expectancy was used as a cut-off point, approximately 3.6 million YPLL resulted from the smoking-attributable deaths.
The average state smoking-attributable mortality rate was 130.0 per 100,000 persons (ranging from 45.3 in Utah to 175.9 in Kentucky).
Editorial Note: Smoking causes more premature deaths than all other health-risk behaviors in the United States. The state- specific calculations of smoking-attributable mortality permit comparison of the impact of smoking with that of other health risks in states. Even as smoking prevalence declines in this country, smoking-attributable illness will continue to produce an enormous disease burden well into the 21st century.Thus, efforts to reduce tobacco use in each state must continue to be a high public health priority.
MMWR, Vol. 37, No. 45, November 18, 1988.
Progress in Chronic Disease Prevention
IV. Smoking-Attributable Mortality, Morbidity, and Economic Costs -- California, 1985
Cigarette smoking remains the single most important preventable cause of death in the United States and has long been implicated as a major risk factor in a variety of chronic diseases, including heart and cerebrovascular diseases, malignant neoplasms, and respiratory and other diseases. Smoking is a major health burden and has important economic effects.
To examine the impact of smoking, the California Department of Health Services, estimated the health and economic costs associated with this risk factor in California for a single year (1985).
In 1985, smoking was directly responsible for 1) 31,289 deaths; 2) 310,018 YPLL; 3) 313,065 hospital discharges; 4) $4.1 billion in hospital and other medical-care costs; and 5) more than $7.1 billion in total costs, including health-care and other costs in the state. Although 77% of the hospital costs related to smoking were paid for by public funds, only 22% of California's adult population currently smokes.
Smoking directly accounts for a substantial portion of the three major causes of death -- heart diseases, malignant neoplasms, and cerebrovascular diseases -- in California and the United States and has been demonstrated or suspected to be a risk factor for a wide variety of other causes of death.
Smoking was responsible for >50% more deaths than were all the following causes combined: unintentional injuries, including motor vehicle collisions and drug-related deaths; homicides; and suicides. Nearly one of every six deaths in the state is attributable to smoking.
MMWR, Vol. 38/No. 16, April 28, 1989.
V.Scombroid Fish Poisoning -- Illinois, South Carolina
Scombroid fish poisoning is an acute syndrome resulting from consumption of fish containing high levels of histamine. This report summarizes investigations of two outbreaks of scombroid fish poisoning in Illinois and South Carolina in 1988.
Illinois. On February 26, 1988, eight cases of scombroid fish poisoning occurred in Chicago in five patrons and three employees of a private club who had eaten a buffet lunch. Six of the ill persons experienced symptoms that included headache, nausea, flushing, dizziness, and diarrhea 90 minutes after the meal. The median duration of symptoms was 9.5 hours. Investigation by the Illinois Department of Public Health revealed that seven of the ill persons had eaten mahi mahi with dill sauce; the eighth had eaten the dill sauce scraped from the serving pan that held the fish. Three persons noted that the fish tasted "Cajun," and one stated that it had a hot or spicy taste.
The club had purchased 10.5 pounds of frozen mahi mahi from a suburban Chicago distributor the week before it was served. The distributor's records revealed that fish from one of two lots of mahi mahi had been sent to the club. On March 1, the state health department placed both lots under embargo. The lots included boxes with evidence of freezer burn, a sign of thawing and refreezing, but these boxes were held by the distributor as damaged goods and not used. The Food and Drug Administration (FDA) tested fish from 17 boxes in these lots; no fish from boxes with evidence of freezer burn were sampled. Six samples had histamine levels > 50 mg/100 g (range: 50-160 mg). The fish was kept in the club's freezer at 0-5 F (-15.0 C - -17.8 C) until February 26, when it was thawed by placing it under running water for 15 minutes. The fish was then cut into portions, placed flat in pans in the cooler, and baked as needed during lunch until the supply was depleted.
South Carolina. In September 1988, nine cases of scombroid fish poisoning in Charleston were investigated by the South Carolina Department of Health and Environmental Control. Of the nine cases, five occurred after consumption of a midday meal at a restaurant September 9, one case followed an evening meal at a second restaurant September 10, and three cases occurred after an evening meal of fish prepared at home but obtained from the first restaurant.
Illness occurred 5-60 minutes after the meal (median time to onset of symptoms: 38 minutes). Symptoms included flushing, diarrhea, headache, feverishness, nausea, rapid pulse, pruritus (itching), dizziness, vomiting, facial swelling, numbness around the mouth, and stomach pain. Symptoms resolved in all persons within 10 hours (median: 6 hours). Five patients required emergency room treatment, and one was admitted for observation because of underlying cardiac disease.
Two persons noted that the fish had a slight peppery taste, and one person noted a metallic taste. All had eaten yellow-fin tuna supplied by the same local distributor. FDA analyses of two samples from the yellow-fin tuna revealed histamine levels of 728 mg/100 g and 583 mg/100 g, respectively.
Editorial Note: During 1973-1986, 178 outbreaks of scombroid poisoning affecting 1096 persons (median: two cases/outbreak) were reported to CDC's Foodborne Disease Outbreak Surveillance System; no fatal cases were reported. Outbreaks have been reported from 30 states and the District of Columbia, with Hawaii reporting the largest number of outbreaks (51), followed by California (29), New York (24), Washington (19), and Connecticut (nine). The fish species was known in 143 (80%) of the scombroid outbreaks; the most commonly reported types were mahi mahi (66 outbreaks), tuna (42 outbreaks), and bluefish (19 outbreaks).
Scombroid poisoning is named for the family Scombridae, which includes tuna and mackerel, but this illness can occur after ingestion of any dark-fleshed nonscombroid species containing high levels of free histidine (amino acid). When these fish are improperly refrigerated, free histidine is broken down to histamine by surface bacteria. This latter compound is thought to produce the clinical manifestations of illness; hence, some investigators have termed this syndrome histamine poisoning. Illness begins minutes to hours after ingestion of the toxic fish. Symptoms resemble a histamine reaction and frequently include dizziness, headache, diarrhea, and a burning sensation or peppery taste in the mouth. Facial flushing, tachycardia (rapid heart rate), pruritus, and asthma-like symptoms can also occur. Illness is usually mild and duration is short, making treatment unnecessary. For more severe cases or in patients with underlying medical conditions, oral antihistamines may be beneficial. Intravenous cimetidine has been anecdotally reported to ameliorate symptoms but its use warrants further study.
Scombroid poisoning is diagnosed by history and clinical symptoms combined with the measurement of histamine levels in implicated fish. Fresh fish normally contains < 1 mg/100 g of histamine; levels of 20 mg/100 g in some species have been reported to produce symptoms. The FDA has established 50 mg/100 g of histamine as a hazardous level in tuna, a level exceeded in both outbreaks in this report. Investigation failed to reveal evidence of improper storage. Experimental studies indicate that histamine formation is low at refrigerator temperatures and negligible in fish stored at < 32 F (< 0 C). As these outbreaks demonstrate, cooking toxic fish is not protective. Therefore, the key to prevention of scombroid poisoning is continuous icing or refrigeration of all potentially scombrotoxic fish from the time they are caught until they are cooked.
MMWR, Vol. 38 / No. 9, March 10, 1989.
VI. Vet Tox Notes: Legal Source of Methylene Blue
FDA has given Sigma Chemical Co., St. Louis, Missouri, permission to sell methylene blue in reagent form to veterinarians. Practitioners may then formulate a 1% methylene blue solution (10 mg/ml in physiologic saline) for prescription use. The dose is 4-15 mg/kg for cattle and sheep. Veterinarians wishing to order methylene blue should call Sigma Food and Drug Department at 1-800-521-8956 Ext. 2389. Prices we have received are $54.65 for 500 gm. An additional special fee of $25 will be added, regardless of order size.
- Abstracted from Ohio Veterinary Newsletter, July 1988. Veterinary News, Vol. 88, No. 4, November 1988.
VII. Review of Federal Pesticide Proposal
A bill (HR 1725) proposed by Representative Waxman and now before Congress, would have considerable impact on California's agriculture if passed.
Currently, pesticide tolerances are established for enforcement purposes; they serve as indicators of whether or not the use regulations are being followed. Risk estimates are based upon risk assessments which are developed from experimental results before tolerances are set. They serve as guides for setting allowable human exposures. Pesticide registrations are based upon an evaluation of the risks and benefits associated with use. This bill will eliminate the risk/benefit approach to pesticide registrations. Permissible pesticide use will be based on estimated health risks. Under the bill, the most conservative models must be used to derive the risk estimates.
The bill requires that tolerances be established for all active and inert ingredients of pesticides on raw or processed commodities. The bill further requires that all tolerances be established so that human dietary exposures will be less than the "negligible risk" level. Negligible risk is defined as the level of human exposure which will not cause or contribute to any known or anticipated adverse human health effects which exceed a rate of one in a million. Any kind of adverse health effect could trigger the standard.
Under the bill, exposure calculations are to be based on total potential dietary exposure. This assumes that 100% of the crop is treated and that residues are equal to 100% of the tolerance. Higher tolerance values could be used only if the actual frequency of crop treatment and residue levels are known, and if the commodity is uniformly distributed and consumed.
The EPA will be compelled to review the registrations for all pesticides and inert ingredients within 180 days of passage of the bill.
Under the proposed law, pesticide and inert ingredient tolerances will become more and more restrictive over a period of six years. Ultimately, the maximum allowed accumulated health risk for all pesticides on a crop will be set at the negligible risk level: all residues combined cannot create a greater than negligible risk. In addition, exposure is to be estimated based on the residues of each individual pesticide or inert ingredient on all commodities which have tolerances, and the total when added together cannot equal a greater than negligible risk.
Sufficient evidence exists in California and elsewhere to demonstrate that actual pesticide residues present on raw and processed agricultural commodities are a minute fraction of the tolerance, and that the actual residues do not constitute a measurable health hazard. Generally, when thorough analyses have been made, pesticide residues have been undetectable. The level of contamination by pesticides is so low that we now recognize that most commercially produced commodities are chemically indistinguishable from those sold as "organically" produced crops. Because the percentage of crops treated and the actual residues present are much lower than the frequency of treatment or maximum residue levels allowed, lowering tolerances cannot change the health risks to consumers. Thus, the actual risks to the consuming public are a small fraction of the levels implied by the authors of this bill. This law will not result in a significant improvement in consumer health by reducing pesticide residues. Please appreciate that this analysis does not represent an official University of California position on the bill.
Pesticide Information Profiles and Toxicology Information Briefs
Each county office has been sent a copy of 100 Pesticide Information Profiles (PIPs) and 20 Toxicology Information Briefs (TIBs) that were developed in a cooperative project called EXTOXNET (Extension Toxicology Network). The cooperators in this program are: the University of California, Davis; Oregon State University; Michigan State University; and Cornell University. The intent behind developing these was that they would be available to anyone who can use them, so please copy and distribute them to clientele. If EXTOXNET ever gets any money to update them, revised PIPs will be sent to replace the old ones. The intent for use is that when distributing these materials, you should include a copy of the 2 page "mini" glossary so clients can have a handy source for "translation". We also have a limited number of copies for sale to private parties for $25/copy (496 pages of materials!). Call Sandy Ogletree for more information.
The main people here at UCD who worked to develop these PIPs are: Allison Beale (a recent graduate of the UCD Pharmacology/Toxicology MS program), Sandy Ogletree, Environmental Toxicology Extension Administrative Assistant; and myself. The main "outsiders" include: Jim Witt, (OSU); Mike Kamrin (MSU); and Barbara Hotchkiss and Donald Rutz (Cornell). Let us know your views of their usefulness.
Used Equipment Available for Use by CE County Staff
We currently have available two functional Osborne Computers for loan to CE staff in the counties. One is a fully functional Osborne I with a dot matrix printer, and the other is an Osborne Executive which needs some work to get the floppy drives back in shape. They are available on a first come, first served basis. Please call Sandy Ogletree if you are interested. Both machines have the standard software that come with them, Wordstar, Supercalc, and the CP/M operating system with Basic.
Statewide Pesticide Coordinator