Mycotoxins in Foods and Feeds in the United States’ Garnett E. Wood Division of Contaminants Chemistry, Food and Drug Administration, Washington, DC 20204
ABSTRACT: Mycotoxins are considered unavoidable contaminants in foods and feeds because agronomic technology has not yet advanced to the stage at which preharvest infection of susceptible crops by fungi can be eliminated. The aflatoxins have received greater attention than any of the other mycotoxins because of their demonstrated carcinogenic effects in susceptible animals and their acute toxic effects in humans. Since 1985, the US.Food and Drug Administration (FDA) has enforced regulatory limits on the concentrations of these toxins in foods and feeds involved in interstate commerce. The FDA routinely monitors the food and feed industries through compliance programs to ensure that the levels of exposure to these toxins are kept as low as practical. This report summarizes data generated from compliance programs on aflatoxins for the fiscal years 1989, 1990, and the first half of
1991. Commodities sampled included peanuts and peanut products, tree nuts, corn and corn products, cottonseed, and milk. Higher than usual levels of contamination were found in corn examined from all areas of the United States in 1989 as a result of the severe drought that affected the 1988 corn crop. The drought in parts of the South and Southeast in 1990 resulted in increased contamination in corn and peanuts from those areas. A review of the surveillance data obtained on deoxynivalenol, zearalenone, ochratoxin A, sterig matocystin, penicillic acid, and patulin over the years along with available toxicological data for these mycotoxins indicated that no regulatory actions were warranted. The lack of sufficient surveillance data on other mycotoxins that occur in the United States can be attributed in part to the unavailability of reliable analytical methodol-
ow-
Key Words: Mycotoxins, Aflatoxins, Corn, Peanuts, Milk, Control Programs ~
J. Anim. Sci. 1992. 70:3941-3949
Introduction The occurrence of mycotoxins in foods and feeds is a problem of major concern, not only in the United States, but all over the world. Various genera of fungi can produce mycotoxins whenever optimal conditions of temperature, humidity, and a suitable substrate prevail in a given area. Many mycotoxins elicit acute, chronic, and subchronic toxicological manifestations in humans and susceptible animals, depending on the concentration and duration of exposure to the toxin and on the age and nutritional state of the animal.
‘Presented at a symposium titled “Current Perspectives on Mycotoxins in Animal Feeds” at the ASAS 83rd Annu. Mtg., Laramie, WY. Received January 21. 1992. Accepted June 8, 1992.
Although hundreds of mycotoxins have been identified, information about many of them is limited with regard to their natural occurrence, stability in foods and feeds, and toxicity to humans. In view of the diversity of toxicological manifestations and the economic losses after exposure to certain mycotoxins, there is a continuous need to protect the health of humans and susceptible animals by limiting their exposure to these toxins. The aflatoxins have been of intense interest to scientists because of their potent carcinogenic effects in susceptible animals and acute toxicological effects in humans. This article will focus on measures being taken by the Food and Drug Administration (FDA) to ensure that the food and feed supplies in the United States are relatively free of aflatoxin contamination. Activities and concerns relating to other mycotoxins will be noted.
3941 Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
WOOD
3942
Program Design Mycotoxins are considered to be unavoidable, added poisonous contaminants in susceptible food and feed crops. It is not possible to predict their presence or to prevent entirely their occurrence during preharvest, storage, and processing opera tions by current agronomic practices. Many countries have enacted legislation that limits the amount of selected mycotoxins permissible in foods and feeds in commercial channels (van Egmond, 1989). In the United States the legal basis for regulating poisonous substances in food is the Federal Food, Drug, and Cosmetic Act, which prohibits the entry of a n adulterated food or feed into interstate commerce. The FDA has enforced regulatory limits on aflatoxins in foods and feed since 1965. The rationale for this action was based on the finding that aflatoxins were potent hepatocarcinogens in some animal species. Therefore, their presence in foods and feeds should be restricted to the minimum concentrations attainable by modern production and processing techG2,and MI are niques. The aflatoxins B1,B2, GI, the only mycotoxins currently being monitored and regulated in the United States. The monitoring efforts for mycotoxins include a formal compliance program and exploratory surveillance activities. The objectives of the compliance program are to collect and analyze samples of foods and feeds to determine compliance with FDA regulatory levels; to remove from interstate commerce those foods and feeds that contain aflatoxins a t concentrations judged to be of regulatory significance; and to determine the awareness of potential problems and control measures employed by distributors, manufacturers, and(or1 processors. The objective of the exploratory surveillance program is to obtain background exposure data for a particular mycotoxin that can be used in conjunction with toxicological data to determine whether a regulatory control program is warranted. The monitoring efforts are directed a t regions and commodities that historically have a high level of contamination or in response to new information on contamination problems developing in regions or commodities not normally affected. An effective monitoring program must include the availability and use of a good sampling plan and reliable analytical techniques. Because mycotoxin contamination in foods and feeds is usually heterogeneous, precautions must be taken in sampling to obtain a reliable quantitative estimate of the concentration of a mycotoxin in a given lot. The errors associated with obtaining an accurate estimate of the true concentration of a toxin in a given lot may occur during sampling, sample preparation, or analysis. Of these, most Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
errors are associated with the sampling technique and the analytical procedure. An overview of sampling and sample preparation preliminary to the identification and quantification of natural toxicants in foods and feeds was published r e cently (Park and Pohland, 1989). All FDA district laboratories involved in monitoring activities are provided with a list of commodities known to be susceptible to aflatoxin contamination, a sampling plan (including product sample size), and a quota of the number of samples to be collected. Sampling of corn, corn-based products, peanut products, milk, and animal feeds is emphasized. Previous incidence data obtained from surveys of small grains such as soybeans, barley, oats, rye, and rice indicated that these grains were not a significant source of aflatoxin exposure unless they were stored improperly. The collected samples are analyzed by official methods specific for each commodity CAOAC, 19901; this analysis is performed mainly a t the Mycotoxin Analytical Laboratory in New Orleans, LA. The limit of detection by the AOAC procedure is 1 ng/g of substrate for aflatoxins in grains, nuts, and their products and .05 ng/mL for aflatoxin M1 in fluid milk products. Regulatory activities are directed in accordance with existing compliance policy guides (Table 1). The FDA announced in 1988 (FDA, 1988) that its current action levels are not binding on the courts, the public (including food processors), or the agency. The current levels do, however, represent the best guidance available on contaminant levels of regulatory interest. The agency intends to initiate notice and comment rule-making proceedings to amend certain of its regulations in the near future.
Discussion Aflatoxins The worldwide occurrence of aflatoxins in foods and feeds is well documented (Stoloff, 1982;Jelinek et al., 1989; Pohland and Wood, 1990). Monitoring data obtained for fiscal years 1989, 1990, and the first half of fiscal year 1991 are presented in Tables 2 through 8. The data highlight the unpredictable occurrence of aflatoxins and the relatively low background concentrations in certain commodities. These data are biased in the sense that the samples collected under compliance programs target those areas and commodities in which one is most likely to find contamination. In other words, they represent a worst-case situation. Even with the bias limitation and the relatively small number of samples involved, it is still possible to find useful trends in the data obtained over a
MYCOTOXINS IN FOODS AND FEEDS Table 1. FDA regulatory levels for total aflatoxinsa
3943
Table 2 . Peanut products examined for aflatoxins and levels
Concentration, Commodity
Determinable aflatoxins, ng/g
ng/g ~~
All products except milk designated for humans Corn for immature animals and dairy cattle Corn for breeding beef cattle, swine, and mature poultry Corn for finishing swine Corn for finishing beef cattle Cottonseed meal (as a feed ingredient) All feedstuff other than corn Milk
20 20 100 200 300 300 20 .5b
*Compliance Policy Guides 7120.28. 7108.10, 7128.33. bAflatoxin MI.
Year
No. of products examined
Percentage of products
Percent age of products
< 20
> 20
1989 1990 1991
158 105 88
1989 1 990 1991
243 95 38
1989 1990 1991
52
.o
14
7.1
.O .O
8
.o
.o
Peanut butter .O
.8 20.0 23.5
3.8 .O
Shelled and roasted .O
.O
14.7 13.1
8.3 2.8
In-shell and roasted
period of years. In all instances, the concentrations of aflatoxin reported refer to total aflatoxins, that is, B1, B2, GI, and G 2 ; M 1 in milk is always reported separately. Peanuts. A formal memorandum of understanding exists between the FDA and United States Department of Agriculture (USDA) on the examination of peanuts for the aflatoxins (Compliance Policy Guides 7155 a.11, 7155 a.13, and 7155 a.14). The USDA, in cooperation with the shellers, is responsible for the analysis and certification of all raw peanuts in commercial channels. The FDA is responsible for testing for aflatoxins in roasted shelled and in-shell peanuts and in processed peanut products. The data in Table 2 reflect an increase in the level of contamination in peanut butter and shelled, roasted peanuts in 1990 and 1991 compared with 1989. Over the years it has been generally observed that roasted, in-shell (‘‘ball p a r k ) peanuts are always the least contaminated of the three products. It is known that roasting destroys at least 5 0 % of the aflatoxin in peanuts. It is thought that the roasting process, coupled with the grade and cultivar used, results in the relative freedom from aflatoxin of the roasted, in-shell peanuts from year to year. Tree Nuts. Aflatoxins were found in almonds, pistachios, and walnuts (Table 3). However, no aflatoxins were found in 13 cashew and filbert/ hazel nut samples. Current techniques of sorting nuts immediately after harvest, followed by cool, dry storage seems to be effective in maintaining a low incidence of contamination of almonds and walnuts in commercial channels. Domestic pistachio nuts have been consistently contaminated to a small extent during the past 5 yr. Contamination in some pistachio nuts has been traced to preharvest splitting of the hull and possible delays between the time of harvest and initiation of the drying process. As a source of aflatoxins in the human diet, tree nuts can be considered a s minor because the per capita consumption of all nuts Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
together is very small compared to that of peanuts and corn. Corn. Corn is the grain most susceptible to aflatoxin contamination in the United States. Aflatoxin contamination in corn is a matter of concern each year in many of the southeastern states where the weather is favorable for the growth of Aspergillus flavus and A. parasiticus. The incidence of contamination by aflatoxins in other states is less frequent, depending on the prevailing weather during the preharvest and harvesting
Table 3. Domestic tree nut products examined for aflatoxin and levels Determinable aflatoxins, ng/g
Year
No. of products examined
1989 1990 1991
108 35 22
1989 1 Q90 1991
212 42 25
Percentage of products
Percentage of products
< 20
> 20
Almond
.o 2.8
.o
.o .o .o
Pecan
.o .o .o
.5 .O
.e
.9
.o
Pistachio 1989 1 990 1991
104
1989 1990 1991
220 52 17
16 15
6.2 20.0
.o 6.8
Walnut 1.7 7.6
2.8 3.8
.o
.o
3 944
WOOD
Table 4. Aflatoxins in shelled corn designated for human consumption Determinable aflatoxins, ng/g Percentage of samples
Percentage of samples
Percent age of samples
Percentage of samples
Percentage of samples
Area of U S .
No. of samples examined
< 20
< 100
c 200
< 300
> 300
Southeasta Corn beltb AR-OK-TX VA-MD Rest of US.
262 736 252 8 261
4.1 9.8 7.1
2.3 3.0 9.1
.7 1.o 1.5
.4
.o
Southeasta Corn beltb AR-OK-TX VA-MD Rest of U S .
24 70 82 0 37
8.0
Southeasta Corn beltb AR-OK-TX VA-MD Rest of us.
38 56 35 0 11
1989
.1
.1
.4
1.5
.o
.O
.o
.o
.O
3.0
4.5
1.5
.8
.8
.o .o
.o
.o
4.0
.O
20.7
1.2
.O .O .O
1.2
1990 4.2 42.8
.o
.o
.o
21.6
2.7
.o .o
.o
.o .o
15.7 5.3 28.5
13.1
7.8
.O
.o
.o
.o
.o
.O
37.1
2.8
.o
.o
.o
9.0
9.0
.O .O
.O .O
.o .o .o
&AL, FL, GA, KY, LA, MS, NC, SC, TN. bIA, IL, IN, KS, MI, MN, MO, NE, OH, SD, WI
contained higher than usual levels of aflatoxin contamination. Accordingly, the compliance program was modified so that a larger than planned number of corn samples was collected and analyzed for aflatoxin contamination. Corn from most areas of the country contained unusually high
periods. Before the drought of 1983, the corn belt states were considered to be aflatoxin-free. The 1988 corn crop in virtually all areas of the United States was subjected to atypical weather conditions during the latter part of the growing season. Because of these conditions, the harvested corn
Table 5. Aflatoxins in shelled corn designated for animal feed Determinable aflatoxins, ng/g Percentage of samples
Percentage of samples
Percentage of samples
Percent age of samples
< 20
< 100
< 200
c 300
5.0 11.4 12.0
5.7 2.6 12.0
1.0 .8 4.0
4.0
.o .o
.o .o
.o .o
.O .O 8.0 .O .O
.o
.o
.o
.o
2.9 11.1
.o
.O
.o
11.1
11.1
22.2
.O
.o .o
.o .o
.o
14.2 1.1
Area of U S .
No. of samples examined
Southeasta Corn beltb AR-TX-OK VA-MD Rest of us.
159 784 25 16 28
Southeasta Corn beltb AR-OK-TX VA-MD Rest of US.
15 136 9 6 7
33.3 38.7
Southeasta Corn beltb AR-OK-TX VA-MD Rest of US.
14 86 11 6
21.4 23.2 18.0 33.3 33.3
Percentage of samples 5
300
1988 .6
.O
.o .O
1990
.O 33.3
.O
.o .o
.o 1991
6
&AL, FL, GA, KY, LA, MS, NC, SC, TN. bIA, IL, IN, KS, MI, MN, MO, NE, OH, SD, WI. Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
35.7 22.0 9.0 50.0
14.2 4.6
.o
.o
.o 18.6
1.1 9.0
.o .o
18.0
.o .O
3945
MYCOTOXINS IN FOODS AND FEEDS
levels of aflatoxin contamination (Tables 4 and 5). The unpredictable nature of the incidence and levels of contamination for a particular area from year to year is evident. The severe drought that occurred in the Southeast and in Texas in 1990 accounts for the increase in aflatoxin contamination in those areas. The data in Table 8 indicate that very little Contamination was observed in milled corn products. Studies have shown that the wet and dry milling processes for corn significantly reduce the aflatoxin content of the finished products used for human consumption. Additionally, cooking processes boiling, baking, and frying) also effectively reduce the aflatoxin content of foods (Scott, 19841. None of the 315 manufactured corn-based products (e.g., corn chips, tortillas, breakfast cereals, popcorn) examined contained aflatoxin concentrations > 20 ng/g. Cottonseed and Cottonseed Meal. Aflatoxin contamination of cottonseed and cottonseed meal may pose a hazard to humans through the consumption of edible animal products. Both of these commodities are used as feed ingredients for animals, including dairy cattle. The incidence of contamination is shown in Table 7. Milk. Aflatoxin M 1is a metabolite of aflatoxin B1 that may be found in the milk of mammals that have ingested aflatoxin B1 in their feed. According to the compliance program, FDA inspectors routinely collect milk for aflatoxin M 1analysis if state
Table 6 . Aflatoxins in milled corn products Determinable aflatoxins, ng/g
Area of US.
No. of samples examined
Percentage of samples
Percentage of samples
< 20
> 20
1989
Southeast' Corn beltb AR-OK-TX VA-MD Rest of US.
155 112 64 16 435
.6 3.5 1.5
Southeasta Corn beltb AR-OK-TX VA-MD Rest of U S .
44 95 14 1 47
18.1 8.4 28.8
.o
.o
6.3
2.1
Southeasta Corn beltb AR-OK-TX VA-MD Rest of U S .
17 48 7 5 12
29.4 6.2 14.2
29.4
.o 9.4
.6
.O
.o .o .o
Table 7. Cottonseed and cottonseed meal lots examined for aflatoxins Determinable aflatoxins, ng/g
Commodity
No. of Percentage lots of lots 5 20 examined
Percentage of lots > 300'
1989
Cottonseed Cottonseed meal
37 27
8.1 22.2
Cottonseed Cottonseed meal
2 17
.o
2.7 7.4 1990
.o .O
17.6 1991
Cottonseed Cottonseed meal
45 6
26.6
11.1 .O
.o
aRegulstory level for cottonseed meal as a feed ingredient.
coverage is inadequate in areas where the potential for aflatoxin in dairy rations exists. The only milk samples containing aflatoxin M1 in excess of .5 ng/mL in 1990 (Table 8) were from the Texas area (Table 81. This corresponded with the drought conditions that affected the corn crop in that state. The contamination noted in 1991 included some states from the corn belt as well as the Southeast and South. The FDA is currently conducting a survey of milk collected throughout the United States for aflatoxin MI in cooperation with the Environmental Protection Agency (EPA1 and the Pasteurized Milk Network, which consists of 68 sampling stations across the United States. Each station collects and submits to the FDA weighted composite samples each month that are representative of at least 41% of the milk consumed in the United States. Results of this 3-yr project should provide important information on background levels and aid in identifying trends in occurrence of aflatoxin M1 in milk throughout the United States. In addition to the FDA aflatoxin-monitoring program, many states are involved in monitoring activities. As of 1989, 14 states had a n active monitoring program for aflatoxins in corn and
1990
.o .o
Table 8. Fluid milk and milk products examined for aflatoxins
.O
Determinable aflatoxins, ng/mL
.o .o
.o .o .O .O
&AL,FL, GA, KY, LA, MS, NC, SC, TN. bIA, IL, IN, KS, MI, MN, MO, NE, OH, SD, WI. Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
No. of products
Percentage of products
Year
No. of products examined
> .5
> .5
1989 1990 1991
632 79 168
8 2 18
1.2 2.5 10.7
3946
WOOD
other selected commodities. Twelve states had no formal monitoring program but were equipped to respond to a n aflatoxin outbreak whenever the need arose. A number of these states have adopted the regulatory limits established by FDA and are actively participating with FDA in a n aflatoxin data exchange program.
Other Mycotoxins Many reports in the literature relate to the occurrence of mycotoxins other than aflatoxins in foods and feeds. A major concern is the accuracy of the data. Of the many analytical methods that have been published and used for obtaining survey data on mycotoxins, only a few have been subjected to formal interlaboratory study. In many cases, confirmation of analyte identity is not included. In view of the large variability associated with determining the mycotoxin concentrations in a given lot of food or feed and the limited numbers of samples analyzed, one must use caution in drawing conclusions about the quantitative results on mycotoxins reported in the literature. For the FDA to establish the need for a formal regulatory control program for a particular mycotoxin, background exposure data are needed as a first step. The following activities relating to other mycotoxins are also of concern to the FDA. Ochrufoxins. The ochratoxins are metabolites produced by certain species of the genera Aspergillus and Penicillium. Ochratoxin A is the major metabolite of toxicological significance and is mainly a contaminant of cereal grains (corn, barley, wheat, and oats). It has also been found in beans (soya, coffee, cocoa), peanuts, and meat in some countries (Krogh, 1987). The results from surveys of corn, wheat, barley, sorghum, and oats conducted by the USDA and FDA between 1967 and 1985 revealed a very low concentration of contamination. Less than 2% of the 2,313 samples examined contained ochratoxin A. (A. E. Pohland, personal communication). The incidence of contamination was highest in barley. No ochratoxin A was found in sorghum. Ochratoxin A is nephrotoxic, teratogenic, and hepatotoxic in certain animal species and is believed to be a causal factor of a particular form of nephropathy observed in humans in the Balkan countries (Bulgaria, Romania, and Yugoslavia; Prior et al., 1983; Krogh, 1987). Recent studies suggest that ochratoxin A is a renal and hepatic carcinogen in mice and rats (Kanizawa, 1984; Bendele et al., 1985; Boorman, 1988; Kuiper-Goodman and Scott, 1989). In view of the latter findings, the FDA initiated a survey in 1989 to determine the incidence and concentrations of ochratoxin A in selected processed products in the United States. The commodities examined included dried peas/ Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
beans, barley (whole/cereals), barley malt, green coffee beans, corn cereals, corn meal, oats (meal, crackers), rice (whole/cereals), rye flour, wheat flour, and soya-based baby food products. Of 351 samples collected and examined, none contained ochratoxin A. The limit of detection of the methodology used was approximately 10 ng/g. The results suggest that ochratoxin A contamination is not a major problem in the United States at this time. However, there is a need for continued surveillance. Zearalenone. Zearalenone is a nonsteroidal, estrogenic mycotoxin produced by Fusarium species. It is associated with reproductive problems in certain animals and possibly in humans. It is mainly a contaminant in corn. However, it may occur in oats, barley, wheat, and sorghum (Mirocha et al., 1976). Surveys for zearalenone in feeds (corn, corn products, wheat, soybean, sorghum) moving in commercial channels in the United States were conducted by the FDA and USDA over a 9-yr period (Bennett and Shotwell, 1979). The results revealed that only 8% of the 1,722 samples examined contained measurable concentrations of the toxin. The incidence and concentrations in corn varied from year to year, depending on the prevailing weather conditions that influenced the planting and harvesting time for a particular area. In two recent surveys of processed grain-based products breakfast cereals, popcorn, snack foods, corn meal, crackers/cookies/muffin mixes) conducted during 1985 and 1989, the same relative concentrations of zearalenone (average 19 to 20 pg/g) were detected each year, despite the adverse weather conditions that prevailed only during the 1989 crop year (Warner and Pestka, 1987; Abouzied et al., 1991). In vivo studies have revealed that zearalenone is rapidly metabolized in animals and humans and eliminated mainly as water-soluble glucuronides (Mirocha et al., 1981).Free and conjugated forms of zearalenone have been found in the milk of lactating cows under experimental conditions (Mirocha et al., 1981). That high oral doses of the toxin are required to elicit such a response indicates that consumption of contaminated feed by dairy cows would not result in a health hazard to humans (Prelusky et al., 1990). An assessment of the health risks associated with the presence of zearalenone in food products in Canada was recently published (Kuiper-Goodman et al., 1987). Tnchothecenes. At least 148 trichothecenes have been isolated and identified, mainly from Fusarium species (Scott, 1990). Deoxynivalenol (DON; vomitoxin), produced by F. graminearurn, is among the most frequent trichothecene contaminants found on cereal crops in the United States. Wheat and corn are particularly affected. Contamination
MYCOTOXINS IN FOODS AND FEEDS of these crops by F. graminearurn usually occurs when harvest is immediately preceded by cool and wet weather conditions (Pathre and Mirocha, 1979). Zearalenone is commonly found to co-occur with DON in the United States. Adverse weather conditions in the central part of the United States during the 1982 crop year resulted in a n unusually high incidence of infection of winter wheat by Fusaria. Surveys of mold-damaged wheat for DON were conducted by the FDA and USDA (Eppley et al., 1984; Shotwell et al., 1985). The data reflected high concentrations (average 3.6 pg/g) of DON in the scabby wheat as well as a good correlation between the occurrence of DON and the degree of scabbiness (grade) of the wheat. Shelled corn collected at various grading stations within the major corn-growing region was examined and found to contain up to 2.14 pg of DON/g (average .35 pg/gl. The FDA issued a n “advisory” to federal and state officials recommending a level of concern for DON of 2 pg of DON/g for wheat entering the milling process, 1 pg/g in finished wheat products for human consumption, and 4 pg/g for wheat and wheat milling by-products used in animal feed (Anonymous, 19821. To assess the potential for human exposure to DON in finished wheat and corn-based products in commercial channels, several surveys were conducted (Brumley et al., 1985; Trucksess et al., 1985; Wood and Carter, 1989; Abouzied et al., 1991). High incidences of DON contamination were reported for various wheat and corn products, including snack foods, breakfast cereals, and oat- and rice-based products. The mean concentration of DON in all positive samples in the most recent survey was > 4 pg/g (Abouzied et al., 1991). Based on current toxicological data, the highest concentration of DON found in the surveys ( > 10 pg/g for two samples) would not present a n acute toxicity risk to humans (Forsell et al., 1987; Ueno, 1987). Deoxynivalenol is rapidly metabolized in all animal species studied. Therefore, residues of DON would not be expected to accumulate in edible tissues to a n extent that would pose a health hazard to humans (Prelusky et al., 1984; Prelusky and Trenholm, 1991). The T-2toxin, produced mainly by Fusarium tricinctum, was the first trichothecene to be found as a naturally occurring grain contaminant in the United States (Hsu et al., 1972). It was associated with a lethal toxicosis in dairy cattle that had consumed moldy corn in Wisconsin. No other confirmed incidence of T-2 toxin has been reported in the United States. This toxin is rarely a s sociated with disorders in animals or humans in other countries (Mirocha, 1984). The chance of finding it as a residue in edible tissue is remote Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
3947
because it is rapidly metabolized in vivo (Yoshizawa et al., 1981). There are no confirmed reports of the occurrence of nivalenol in the United States. The cooccurrence of nivalenol with DON in cereal grains in Canada, Japan, and other countries has been well documented (Scott, 1990). PatuZin and PeniciZlic Acid. Patulin is a toxic metabolite of several fungal genera, including Penicillia. The natural occurrence of patulin has been associated with soft rot in apples and other fruits. If the fruit contains sulfhydryl compounds in a n amount sufficient to bind all patulin produced, it will not be a problem (Scott and Somers, 1968). In view of its instability in foods rich in sulfhydryl compounds (grains, meats, and cheese) and its low oral toxicity in animals studied, patulin does not seem to be of real concern in the United States (Becci et al., 1981; Harrison, 1989). Penicillic acid is also produced by species of Penicillia. This toxin has been found in “blue eye” corn and dried beans (Thorpe and Johnson, 1974). Limited reports on the occurrence of penicillic acid in foods may be attributed to its property of reacting with sulfhydryl compounds in a manner similar to that of patulin. Citn’nin. Citrinin, produced by species of the genera Penicillia, is usually found in feedstuff as a co-contaminant with ochratoxin. Citrinin is a nephrotoxin, like ochratoxin A, and causes lesions in many animal species and, specifically, renal tumors in rats (Arai and Hibino, 1983). Unfortunately, no satisfactory analytical methods are available for this mycotoxin. Therefore, incidences and concentrations reported in foods and feeds are not reliable. There are no confirmed reports of the occurrence of citrinin in the United States. CycZopiazonic Acid. Cyclopiazonic acid (CPAI is produced by several Penicillia species and by A. flavus. It has been found naturally in corn, cheese, and visibly molded peanuts (Gallagher et al., 1978; LeBars, 1979; Lansden and Davidson, 1983). Because analytical methods for CPA are not well developed, there are no survey data relating to incidence and concentrations in susceptible commodities. The acute toxicity of CPA is low in the animal species studied, and there are no chronic toxicity data currently available (Norred, 1990). Sterigmatocystin. Sterigmatocystin is produced by several species of the genus Aspergillus and by other fungal genera. It is of concern because its structure is very similar to that of aflatoxin and it also exhibits carcinogenic and mutagenic properties (Purchase and van der Watt, 1973; Ueno et al., 19781. Although the genera that produce this toxin are widely distributed among agricultural commodities, there are very few reports on the natural
3948
WOOD
occurrence of this toxin (Schroeder and Hein, 1977; Northolt et al., 1980). In a survey conducted by the FDA during 1974 and 1975, no sterigmatocystin was found in any of 574 grain samples examined (Stoloff, 1982). Alternaria. Fungi of the genus Alternaria are commonly found in the soil and are frequently encountered on agricultural products after harvest. The major mycotoxins produced by species of this genus include alternariol, alternariol methyl ether, altenuene, altertoxin-1, and tenuazonic acid. In the United States, some of these mycotoxins have been found in damaged grains and nuts and in infected fruits and vegetables (Seitz et al., 1975; Schroeder and Cole, 1977; Stinson et al., 1981; Stack et al., 1985). Because current survey (incidence/concentrations) and toxicological data are insufficient, the hazards associated with these toxins in foods and feeds cannot be assessed. Ergot Alkaloids. The ergot alkaloids are found in the sclerotia formed by Claviceps purpura and other fungal species on cereal grains. These alkaloids are responsible for the human disease ergotism, which is rarely reported today. The enforcement of grading standards and the cleaning, milling, and thermal processes used for cereal grains have greatly reduced the concentration of these alkaloids present in commercial products (Scott and Lawrence, 1982). In the United States, ergot alkaloids are believed to be responsible for the toxicity of tall fescue grass to cattle (Lyons et al., 19861. Fumonisins.The Fumonisins (FB1 and FB$ were recently isolated from Fusarium moniliforme cultures and found to promote cancer in rats (Gelderblom et al., 1988). These toxins occur naturally in corn and have been associated with equine leukoencephalomalacia and porcine pulmonary edema syndrome in the United States (Ross et al., 1990; Wilson et al., 19901. Although several analytical methods have been published, only one has been subjected to a collaborative study, and the results of that study have not yet been published. An intragovernmental research committee was recently formed (FDA-USDN to oversee the status of developing research. Its aim is to identify and support research for regulatory needs, to aid in development of analytical methods (including rapid screening tests), and to encourage additional government and private funding for fumonisin research.
Implications The surveillance and regulatory programs of the Food and Drug Administration for mycotoxins are designed to keep the amount in foods and Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
feeds a t the lowest concentrations attainable and are consistent with maintaining a n adequate commodity supply at a reasonable cost. Human exposure to aflatoxins in the United States is relatively low. The monitoring efforts of the Food and Drug Administration are complemented by control programs carried out by USDA, state departments of agriculture, and various trade associations. Data on incidences and concentrations of various mycotoxins in the United States can be coupled with toxicological data so that estimates of human risks can be made and regulatory limits imposed when warranted.
Literature Cited Abouzied, M. M., J. I. Azcona, W. E. Braselton, and J. J. Pestka. 1991. Immunochemical assessment of mycotoxins in 1989 grain foods: Evidence for deoxynivalenol (vomitoxid c o n tamination. Appl. Environ. Microbiol. 57372. Anonymous. 1982. Food Chem. News 24:3. AOAC. 1990. Official Methods of Analysis (15th Ed.). Association of Official Analytical Chemists, Arlington, VA. Arai, M., and T. Hibino. 1983. Tumorigenicity of citrinin in male F344 rats. Cancer Lett. 7:281. Becci, P. J., F. G. Hess, W. D. Johnson, M. A. Gallo, J. G. Bobish, R. E. Dailey, and R. A. Parent. 1981. Long-term carcinogenicity and toxicity studies of patulin in rats. J. Appl. Tox icol. 1:256. Bendele, A. M., W. W. Carlton, P. Krogh, and E. B. Lillehoj. 1985. Ochratoxin A carcinogenesis in the (C57BL/BJXC 3H) F1 mouse. J. Natl. Cancer Inst. 75:733. Bennett, G. A., and 0. L. Shotwell. 1979. Zearalenone in cereal grains. J. Am. Oil Chem. SOC.56:812. Boorman, G. 1988. NTP Technical report on the toxicology and carcinogenesis studies of ochratoxin A (CAS No. 303.47-9)in F344/N rats (gavage studies), NIH Publ. No. 89-2813. US. Dept. of Health and Human Services, National Institutes of Health, Research Triangle Park, NC. Brumley, W. C., M. W. Trucksess, S. H. Adler, C. K. Cohen, K. D. White, and J. A. Sphon. 1985. Negative ion chemical ionization mass spectrometry of deoxynivalenol (DON):Application to identification of DON in grains and snack foods after quantitation/isolation by thin layer chromatography. J. Agric. Food Chem. 33:326. Eppley, R.M., M. W. Trucksess, S.Nesheim, C. W. Thorpe, G. E. Wood, and A. E. Pohland. 1984. Deoxynivalenol in winter wheat: Thin layer chromatographic method and survey. J. Assoc. Off. Anal. Chem. 67:43. FDA. 1988. Action levels for added poisonous or deleterious substances in food. Fed. Regist. 53:5043. Forsell, J. H., R. Jensen, J. H. Tai, M. Witt, W. S. Lin, and J. J. Pestka. 1987. Comparison of acute toxicities of deox ynivalenol (vomitoxinl and 15-acetyldeoxynivalenol in the BBCBFl mouse. Food Chem. Toxicol. 25:155. Gallagher, R.T., J. L. Richard, H. M. Stahr, and R. J. Cole. 1978. Cyclopiazonic acid production by aflatoxigenic and Aspergillus pavus. nonaflatoxigenic strains of Mycopathologia 66:31. Gelderblom, W.C.A.,K. Jaskiewicz, W.F.O. Marasas, P. G. Thiel, R. M. Horak, R. Vleggaar, and N.P.J. Kriek. 1988. Fumonisins-novel mycotoxins with cancer-promoting activity produced by Fusarium monilifome. Appl. Environ. Microbiol. 54:1806. Harrison, M. A. 1989. Presence and stability of patulin in apple products: A review. J. Food Saf. 9:147.
MYCOTOXINS IN FOODS AND FEEDS Hsu, 1.H.-C.,E. B. Smalley, F. M. Strong, and W. E. Ribelin. 1972. Identification of T-2toxin in moldy corn associated with a lethal toxicosis in dairy cattle. Appl. Microbiol. 24:684. Jelinek, C. F., A. E. Pohland, and G.E. Wood. 1989. Worldwide occurrence of mycotoxins in foods and feeds-an update. J. Assoc. Off. Anal. Chem. 72:223. Kanizawa, M. 1984. Synergistic effect of citrinin on hepatorenal carcinogenesis of OA in mice. In: H. Kurata and Y. Ueno (Ed.) Toxigenic Fungi-Their Toxins and Health Hazard. p 245. Elsevier, Amsterdam. Krogh, P. 1987. Ochratoxins in food. I n P. Krogh (Ed.)Mycotox ins in Food. p 97. Academic Press, London. Kuiper-Goodman, T., and P. M. Scott. 1989. Risk assessment of the mycotoxin ochratoxin A. Biomed. Environ. Sci. 2:179. Kuiper-Goodman, T., P. M. Scott and H. Watanabe. 1987. Risk assessment of the mycotoxin zearalenone. Reg. Toxicol. Pharmacol. 7:253. Lansden, J. A., and J. I. Davidson. 1983. Occurrence of cyclopiazonic acid in peanuts. Appl. Environ. Microbol. 45:766. LeBars, J. 1979. Cyclopiazonic acid production by Penicillium camemberti Thorn and natural occurrence of this mycotoxin in cheese. Appl. Environ. Microbiol. 38:1052. Lyons, P. C., R. D. Plattner, and C. W. Bacon. 1986. Occurrence of peptide and clavine ergot alkaloids in tall fescue grass. Science 232:487. Mirocha, C. J. 1984. Mycotoxicoses associated with Fusarium. In: M. 0. Moss and J. E. Smith [Ed.) The Applied Mycology of Fusarium. p 141. Cambridge University Press, U.K. Mirocha, C. J., S. V. Pathre, andT. S.Robison. 1981. Comparative metabolism of zearalenone and transmission into bovine milk. Food Cosmet. Toxicol. 19:25. Mirocha, C. J., S. V. Pathre, B. Schauerhamer, and C. M. Christensen. 1976. Natural occurrence of Fusarium toxin in feedstuff. Appl. Environ. Microbiol. 32:553. Norred, W. P. 1990. Cyclopiazonic acid: toxicity and tissue distribution. Vet. Hum. Toxicol. 32(Suppl.):20. Northolt, M. D., H. P. van Egmond, P. Soentoro, and E. Deijll. 1980. Fungal growth and presence of sterigmatocystin in hard cheese. J. Assoc. Off. Anal. Chem. 63:115. Park, D. L., and A. E. Pohland. 1989. Sampling and sample preparation for detection and quantitation of natural toxicants in food and feed. J. Assoc. Off.Anal. Chem. 72:399. Pathre, S. V., and C. J. Mirocha. 1979. Trichothecenes: natural occurrence and potential hazard. J. Am. Oil Chem. SOC.56: 820.
Pohland, A. E., and G. E. Wood. 1990. Natural occurrence of mycotoxins. I n G.A. Bray and D. H. Ryan (Ed.) Mycotox. ins, Cancer and Health. Pennington Center Nutritional Series, Vol. 1. Louisiana State University Press, Baton Rouge. Prelusky, D. B., P. M. Scott, H. L. Trenholm, and G. A. Lawrence. 1990. Minimal transmission of zearalenone to milk of dairy cows. 3. Environ. Sci. Health B25:87. Perlusky, D. B., and H. L. Trenholm. 1991. Tissue distribution of deoxynivalenol in swine dosed intravenously. J. Agric. Food Chem. 39:748. Prelusky, D. B., H. L. Trenholm, G. A. Lawrence, and P. M. Scott. 1984. Nontransmission of deoxynivalenol (vomitoxin) to milk following oral administration to dairy cows. J. Environ. Sci. Health B19:593. Prior, M. G., C. S. Sisodia, and F. Hrudka. 1983. Some cellular effects of ochratoxin A. Toxicon 3(Suppl.l:353. Purchase, I.F.H., and J. J. van der Watt. 1973. Carcinogenicity of sterigmatocystin to rat skin. Toxicol. Appl. Pharmacol. 26: 274.
Ross,P. F., P. E. Nelson, J. L. Richard, G. D. Osweiler, L. G. Rice, R. D. Plattner, and T. M. Wilson. 1990. Production of fumonisins by Fusarium monilifonne and Fusarium prolifeeraturn isolates associated with equine leukoen-
Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
3949
cephalomalacia and a pulmonary edema syndrome in swine. Appl. Environ. Microbiol. 56:3225. Schroeder, H. W., and R. J. Cole. 1977. Natural occurrence of alternariols in discolored pecans. J. Agric. Food Chem. 25: 204.
Schroeder, H. W., and H. Hein. 1977. Natural occurrence of sterigmatocystin in in-shell pecans. Can. J. Microbiol. 23: 639.
Scott, P. M. 1984. Effects of processing on mycotoxins. J. Food h o t . 41:489. Scott, P. M. 1990. Trichothecenes in grains. Cereal Foods World 35:661.
Scott, P. M., and G. A. Lawrence. 1982. Losses of ergot alkaloids during making of bread and pancakes. J. Agric. Food Chem. 30:445. Scott, P. M.. and E. Somers. 1968. Stability of patulin and penicillic acid in fruit juices and flour. J. Agric. Food Chem. 16:483.
Seitz, L. M., D. B. Sauer, H. E. Mohr, and R. Burroughs. 1975. Weathered grain sorghum: Natural occurrence of alternariols and storability of the grain. Phytopathology 65:1259. Shotwell, 0. L., G.A. Bennett, R. D. Stubblefield, G. M. Shannon, W. F. Kwolek, and E. D. Plattner. 1965. Deoxynivalenol in hard red wheat: Relationship between toxin levels and grading factors. J. Assoc. Off. Anal. Chem. 88:954. Stack, M. E., P. B. Mislivec, J.A.G. Roach, and A. E. Pohland. 1985. Liquid chromatographic determination of tenuazonic acid and alternariol methyl ether in tomatoes and tomato products. J. Assoc. Off. Anal. Chem. 68:640. Stinson, E. E., D. F. Osman, E. G. Heisler, J. Siciliand, and D. D. Bills. 1981. Mycotoxin production in whole tomatoes, a p ples, oranges and lemons. J. Agric. Food Chem. 29:790. Stoloff, L. 1982. Mycotoxins as potential environmental carcinogens. I n H. F. Stich (Ed.)Carcinogens and Mutagens in the Environment. Val. 1. p 88. CRC Press, Boca Raton. FL. Thorpe, C. W., and R. L. Johnson. 1974. Analysis of penicillic acid by gas-liquid chromatography. J. Assoc. Off. Anal. Chem. 57:861. Trucksess, M. W., G. E. Wood, R. M. Eppley, K. Young, C. K. Cohen, S. W. Page, and A. E. Pohland. 1985. Occurrence of deoxynivalenol in grain and grain products. Biodeterioration 6:243. Ueno, Y. 1987. Trichothecenes in food. In: P. Krogh (Ed.) Mycotoxins in Food. p 123. Academic Press, London. Ueno, Y., K. Kubota, T. Ito, and Y. Nakamura. 1978. Mutagenicity of carcinogenic mycotoxins in Salmonella typhimurium. Cancer Res. 38538. van Egmond, H. P. 1989. Current situation on regulations for mycotoxins. Overview of tolerances and status of standard methods of sampling and analysis. Food Addit. Contam. 6: 139.
Warner, R. L., and J. J. Pestka. 1987. ELISA survey of retail grain-based food products for zearalenone and aflatoxin B1. J. Food Prot. 50:502. Wilson, T. M., P. F. Ross, L. G. Rice, G. D. Osweiler, H. A. Nelson, D. L. Owens, R. D. Plattner, C. Reggiardo, T. H. Noon, and J. W. Pickrell. 1890. Fumonisin B1 levels associated with an epizootic of equine leukoencephalomalacia. J. Vet. Diagn. Invest. 2:213. Wood, G. E., and L. Carter. 1989. Limited survey of deoxynivalenol in wheat and corn in the United States. J. Assoc. Off. Anal. Chem. 72:38. Yoshizawa, T., C. J. Mirocha, J. C. Behrens, and S. P. Swanson. 1981. Metabolic fate of T-2 toxin in a lactating cow. Food Cosmet. Toxicol. 19:31.
ABSTRACT: Mycotoxins are considered unavoidable contaminants in foods and feeds because agronomic technology has not yet advanced to the stage at which preharvest infection of susceptible crops by fungi can be eliminated. The aflatoxins have received greater attention than any of the other mycotoxins because of their demonstrated carcinogenic effects in susceptible animals and their acute toxic effects in humans. Since 1985, the US.Food and Drug Administration (FDA) has enforced regulatory limits on the concentrations of these toxins in foods and feeds involved in interstate commerce. The FDA routinely monitors the food and feed industries through compliance programs to ensure that the levels of exposure to these toxins are kept as low as practical. This report summarizes data generated from compliance programs on aflatoxins for the fiscal years 1989, 1990, and the first half of
1991. Commodities sampled included peanuts and peanut products, tree nuts, corn and corn products, cottonseed, and milk. Higher than usual levels of contamination were found in corn examined from all areas of the United States in 1989 as a result of the severe drought that affected the 1988 corn crop. The drought in parts of the South and Southeast in 1990 resulted in increased contamination in corn and peanuts from those areas. A review of the surveillance data obtained on deoxynivalenol, zearalenone, ochratoxin A, sterig matocystin, penicillic acid, and patulin over the years along with available toxicological data for these mycotoxins indicated that no regulatory actions were warranted. The lack of sufficient surveillance data on other mycotoxins that occur in the United States can be attributed in part to the unavailability of reliable analytical methodol-
ow-
Key Words: Mycotoxins, Aflatoxins, Corn, Peanuts, Milk, Control Programs ~
J. Anim. Sci. 1992. 70:3941-3949
Introduction The occurrence of mycotoxins in foods and feeds is a problem of major concern, not only in the United States, but all over the world. Various genera of fungi can produce mycotoxins whenever optimal conditions of temperature, humidity, and a suitable substrate prevail in a given area. Many mycotoxins elicit acute, chronic, and subchronic toxicological manifestations in humans and susceptible animals, depending on the concentration and duration of exposure to the toxin and on the age and nutritional state of the animal.
‘Presented at a symposium titled “Current Perspectives on Mycotoxins in Animal Feeds” at the ASAS 83rd Annu. Mtg., Laramie, WY. Received January 21. 1992. Accepted June 8, 1992.
Although hundreds of mycotoxins have been identified, information about many of them is limited with regard to their natural occurrence, stability in foods and feeds, and toxicity to humans. In view of the diversity of toxicological manifestations and the economic losses after exposure to certain mycotoxins, there is a continuous need to protect the health of humans and susceptible animals by limiting their exposure to these toxins. The aflatoxins have been of intense interest to scientists because of their potent carcinogenic effects in susceptible animals and acute toxicological effects in humans. This article will focus on measures being taken by the Food and Drug Administration (FDA) to ensure that the food and feed supplies in the United States are relatively free of aflatoxin contamination. Activities and concerns relating to other mycotoxins will be noted.
3941 Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
WOOD
3942
Program Design Mycotoxins are considered to be unavoidable, added poisonous contaminants in susceptible food and feed crops. It is not possible to predict their presence or to prevent entirely their occurrence during preharvest, storage, and processing opera tions by current agronomic practices. Many countries have enacted legislation that limits the amount of selected mycotoxins permissible in foods and feeds in commercial channels (van Egmond, 1989). In the United States the legal basis for regulating poisonous substances in food is the Federal Food, Drug, and Cosmetic Act, which prohibits the entry of a n adulterated food or feed into interstate commerce. The FDA has enforced regulatory limits on aflatoxins in foods and feed since 1965. The rationale for this action was based on the finding that aflatoxins were potent hepatocarcinogens in some animal species. Therefore, their presence in foods and feeds should be restricted to the minimum concentrations attainable by modern production and processing techG2,and MI are niques. The aflatoxins B1,B2, GI, the only mycotoxins currently being monitored and regulated in the United States. The monitoring efforts for mycotoxins include a formal compliance program and exploratory surveillance activities. The objectives of the compliance program are to collect and analyze samples of foods and feeds to determine compliance with FDA regulatory levels; to remove from interstate commerce those foods and feeds that contain aflatoxins a t concentrations judged to be of regulatory significance; and to determine the awareness of potential problems and control measures employed by distributors, manufacturers, and(or1 processors. The objective of the exploratory surveillance program is to obtain background exposure data for a particular mycotoxin that can be used in conjunction with toxicological data to determine whether a regulatory control program is warranted. The monitoring efforts are directed a t regions and commodities that historically have a high level of contamination or in response to new information on contamination problems developing in regions or commodities not normally affected. An effective monitoring program must include the availability and use of a good sampling plan and reliable analytical techniques. Because mycotoxin contamination in foods and feeds is usually heterogeneous, precautions must be taken in sampling to obtain a reliable quantitative estimate of the concentration of a mycotoxin in a given lot. The errors associated with obtaining an accurate estimate of the true concentration of a toxin in a given lot may occur during sampling, sample preparation, or analysis. Of these, most Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
errors are associated with the sampling technique and the analytical procedure. An overview of sampling and sample preparation preliminary to the identification and quantification of natural toxicants in foods and feeds was published r e cently (Park and Pohland, 1989). All FDA district laboratories involved in monitoring activities are provided with a list of commodities known to be susceptible to aflatoxin contamination, a sampling plan (including product sample size), and a quota of the number of samples to be collected. Sampling of corn, corn-based products, peanut products, milk, and animal feeds is emphasized. Previous incidence data obtained from surveys of small grains such as soybeans, barley, oats, rye, and rice indicated that these grains were not a significant source of aflatoxin exposure unless they were stored improperly. The collected samples are analyzed by official methods specific for each commodity CAOAC, 19901; this analysis is performed mainly a t the Mycotoxin Analytical Laboratory in New Orleans, LA. The limit of detection by the AOAC procedure is 1 ng/g of substrate for aflatoxins in grains, nuts, and their products and .05 ng/mL for aflatoxin M1 in fluid milk products. Regulatory activities are directed in accordance with existing compliance policy guides (Table 1). The FDA announced in 1988 (FDA, 1988) that its current action levels are not binding on the courts, the public (including food processors), or the agency. The current levels do, however, represent the best guidance available on contaminant levels of regulatory interest. The agency intends to initiate notice and comment rule-making proceedings to amend certain of its regulations in the near future.
Discussion Aflatoxins The worldwide occurrence of aflatoxins in foods and feeds is well documented (Stoloff, 1982;Jelinek et al., 1989; Pohland and Wood, 1990). Monitoring data obtained for fiscal years 1989, 1990, and the first half of fiscal year 1991 are presented in Tables 2 through 8. The data highlight the unpredictable occurrence of aflatoxins and the relatively low background concentrations in certain commodities. These data are biased in the sense that the samples collected under compliance programs target those areas and commodities in which one is most likely to find contamination. In other words, they represent a worst-case situation. Even with the bias limitation and the relatively small number of samples involved, it is still possible to find useful trends in the data obtained over a
MYCOTOXINS IN FOODS AND FEEDS Table 1. FDA regulatory levels for total aflatoxinsa
3943
Table 2 . Peanut products examined for aflatoxins and levels
Concentration, Commodity
Determinable aflatoxins, ng/g
ng/g ~~
All products except milk designated for humans Corn for immature animals and dairy cattle Corn for breeding beef cattle, swine, and mature poultry Corn for finishing swine Corn for finishing beef cattle Cottonseed meal (as a feed ingredient) All feedstuff other than corn Milk
20 20 100 200 300 300 20 .5b
*Compliance Policy Guides 7120.28. 7108.10, 7128.33. bAflatoxin MI.
Year
No. of products examined
Percentage of products
Percent age of products
< 20
> 20
1989 1990 1991
158 105 88
1989 1 990 1991
243 95 38
1989 1990 1991
52
.o
14
7.1
.O .O
8
.o
.o
Peanut butter .O
.8 20.0 23.5
3.8 .O
Shelled and roasted .O
.O
14.7 13.1
8.3 2.8
In-shell and roasted
period of years. In all instances, the concentrations of aflatoxin reported refer to total aflatoxins, that is, B1, B2, GI, and G 2 ; M 1 in milk is always reported separately. Peanuts. A formal memorandum of understanding exists between the FDA and United States Department of Agriculture (USDA) on the examination of peanuts for the aflatoxins (Compliance Policy Guides 7155 a.11, 7155 a.13, and 7155 a.14). The USDA, in cooperation with the shellers, is responsible for the analysis and certification of all raw peanuts in commercial channels. The FDA is responsible for testing for aflatoxins in roasted shelled and in-shell peanuts and in processed peanut products. The data in Table 2 reflect an increase in the level of contamination in peanut butter and shelled, roasted peanuts in 1990 and 1991 compared with 1989. Over the years it has been generally observed that roasted, in-shell (‘‘ball p a r k ) peanuts are always the least contaminated of the three products. It is known that roasting destroys at least 5 0 % of the aflatoxin in peanuts. It is thought that the roasting process, coupled with the grade and cultivar used, results in the relative freedom from aflatoxin of the roasted, in-shell peanuts from year to year. Tree Nuts. Aflatoxins were found in almonds, pistachios, and walnuts (Table 3). However, no aflatoxins were found in 13 cashew and filbert/ hazel nut samples. Current techniques of sorting nuts immediately after harvest, followed by cool, dry storage seems to be effective in maintaining a low incidence of contamination of almonds and walnuts in commercial channels. Domestic pistachio nuts have been consistently contaminated to a small extent during the past 5 yr. Contamination in some pistachio nuts has been traced to preharvest splitting of the hull and possible delays between the time of harvest and initiation of the drying process. As a source of aflatoxins in the human diet, tree nuts can be considered a s minor because the per capita consumption of all nuts Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
together is very small compared to that of peanuts and corn. Corn. Corn is the grain most susceptible to aflatoxin contamination in the United States. Aflatoxin contamination in corn is a matter of concern each year in many of the southeastern states where the weather is favorable for the growth of Aspergillus flavus and A. parasiticus. The incidence of contamination by aflatoxins in other states is less frequent, depending on the prevailing weather during the preharvest and harvesting
Table 3. Domestic tree nut products examined for aflatoxin and levels Determinable aflatoxins, ng/g
Year
No. of products examined
1989 1990 1991
108 35 22
1989 1 Q90 1991
212 42 25
Percentage of products
Percentage of products
< 20
> 20
Almond
.o 2.8
.o
.o .o .o
Pecan
.o .o .o
.5 .O
.e
.9
.o
Pistachio 1989 1 990 1991
104
1989 1990 1991
220 52 17
16 15
6.2 20.0
.o 6.8
Walnut 1.7 7.6
2.8 3.8
.o
.o
3 944
WOOD
Table 4. Aflatoxins in shelled corn designated for human consumption Determinable aflatoxins, ng/g Percentage of samples
Percentage of samples
Percent age of samples
Percentage of samples
Percentage of samples
Area of U S .
No. of samples examined
< 20
< 100
c 200
< 300
> 300
Southeasta Corn beltb AR-OK-TX VA-MD Rest of US.
262 736 252 8 261
4.1 9.8 7.1
2.3 3.0 9.1
.7 1.o 1.5
.4
.o
Southeasta Corn beltb AR-OK-TX VA-MD Rest of U S .
24 70 82 0 37
8.0
Southeasta Corn beltb AR-OK-TX VA-MD Rest of us.
38 56 35 0 11
1989
.1
.1
.4
1.5
.o
.O
.o
.o
.O
3.0
4.5
1.5
.8
.8
.o .o
.o
.o
4.0
.O
20.7
1.2
.O .O .O
1.2
1990 4.2 42.8
.o
.o
.o
21.6
2.7
.o .o
.o
.o .o
15.7 5.3 28.5
13.1
7.8
.O
.o
.o
.o
.o
.O
37.1
2.8
.o
.o
.o
9.0
9.0
.O .O
.O .O
.o .o .o
&AL, FL, GA, KY, LA, MS, NC, SC, TN. bIA, IL, IN, KS, MI, MN, MO, NE, OH, SD, WI
contained higher than usual levels of aflatoxin contamination. Accordingly, the compliance program was modified so that a larger than planned number of corn samples was collected and analyzed for aflatoxin contamination. Corn from most areas of the country contained unusually high
periods. Before the drought of 1983, the corn belt states were considered to be aflatoxin-free. The 1988 corn crop in virtually all areas of the United States was subjected to atypical weather conditions during the latter part of the growing season. Because of these conditions, the harvested corn
Table 5. Aflatoxins in shelled corn designated for animal feed Determinable aflatoxins, ng/g Percentage of samples
Percentage of samples
Percentage of samples
Percent age of samples
< 20
< 100
< 200
c 300
5.0 11.4 12.0
5.7 2.6 12.0
1.0 .8 4.0
4.0
.o .o
.o .o
.o .o
.O .O 8.0 .O .O
.o
.o
.o
.o
2.9 11.1
.o
.O
.o
11.1
11.1
22.2
.O
.o .o
.o .o
.o
14.2 1.1
Area of U S .
No. of samples examined
Southeasta Corn beltb AR-TX-OK VA-MD Rest of us.
159 784 25 16 28
Southeasta Corn beltb AR-OK-TX VA-MD Rest of US.
15 136 9 6 7
33.3 38.7
Southeasta Corn beltb AR-OK-TX VA-MD Rest of US.
14 86 11 6
21.4 23.2 18.0 33.3 33.3
Percentage of samples 5
300
1988 .6
.O
.o .O
1990
.O 33.3
.O
.o .o
.o 1991
6
&AL, FL, GA, KY, LA, MS, NC, SC, TN. bIA, IL, IN, KS, MI, MN, MO, NE, OH, SD, WI. Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
35.7 22.0 9.0 50.0
14.2 4.6
.o
.o
.o 18.6
1.1 9.0
.o .o
18.0
.o .O
3945
MYCOTOXINS IN FOODS AND FEEDS
levels of aflatoxin contamination (Tables 4 and 5). The unpredictable nature of the incidence and levels of contamination for a particular area from year to year is evident. The severe drought that occurred in the Southeast and in Texas in 1990 accounts for the increase in aflatoxin contamination in those areas. The data in Table 8 indicate that very little Contamination was observed in milled corn products. Studies have shown that the wet and dry milling processes for corn significantly reduce the aflatoxin content of the finished products used for human consumption. Additionally, cooking processes boiling, baking, and frying) also effectively reduce the aflatoxin content of foods (Scott, 19841. None of the 315 manufactured corn-based products (e.g., corn chips, tortillas, breakfast cereals, popcorn) examined contained aflatoxin concentrations > 20 ng/g. Cottonseed and Cottonseed Meal. Aflatoxin contamination of cottonseed and cottonseed meal may pose a hazard to humans through the consumption of edible animal products. Both of these commodities are used as feed ingredients for animals, including dairy cattle. The incidence of contamination is shown in Table 7. Milk. Aflatoxin M 1is a metabolite of aflatoxin B1 that may be found in the milk of mammals that have ingested aflatoxin B1 in their feed. According to the compliance program, FDA inspectors routinely collect milk for aflatoxin M 1analysis if state
Table 6 . Aflatoxins in milled corn products Determinable aflatoxins, ng/g
Area of US.
No. of samples examined
Percentage of samples
Percentage of samples
< 20
> 20
1989
Southeast' Corn beltb AR-OK-TX VA-MD Rest of US.
155 112 64 16 435
.6 3.5 1.5
Southeasta Corn beltb AR-OK-TX VA-MD Rest of U S .
44 95 14 1 47
18.1 8.4 28.8
.o
.o
6.3
2.1
Southeasta Corn beltb AR-OK-TX VA-MD Rest of U S .
17 48 7 5 12
29.4 6.2 14.2
29.4
.o 9.4
.6
.O
.o .o .o
Table 7. Cottonseed and cottonseed meal lots examined for aflatoxins Determinable aflatoxins, ng/g
Commodity
No. of Percentage lots of lots 5 20 examined
Percentage of lots > 300'
1989
Cottonseed Cottonseed meal
37 27
8.1 22.2
Cottonseed Cottonseed meal
2 17
.o
2.7 7.4 1990
.o .O
17.6 1991
Cottonseed Cottonseed meal
45 6
26.6
11.1 .O
.o
aRegulstory level for cottonseed meal as a feed ingredient.
coverage is inadequate in areas where the potential for aflatoxin in dairy rations exists. The only milk samples containing aflatoxin M1 in excess of .5 ng/mL in 1990 (Table 8) were from the Texas area (Table 81. This corresponded with the drought conditions that affected the corn crop in that state. The contamination noted in 1991 included some states from the corn belt as well as the Southeast and South. The FDA is currently conducting a survey of milk collected throughout the United States for aflatoxin MI in cooperation with the Environmental Protection Agency (EPA1 and the Pasteurized Milk Network, which consists of 68 sampling stations across the United States. Each station collects and submits to the FDA weighted composite samples each month that are representative of at least 41% of the milk consumed in the United States. Results of this 3-yr project should provide important information on background levels and aid in identifying trends in occurrence of aflatoxin M1 in milk throughout the United States. In addition to the FDA aflatoxin-monitoring program, many states are involved in monitoring activities. As of 1989, 14 states had a n active monitoring program for aflatoxins in corn and
1990
.o .o
Table 8. Fluid milk and milk products examined for aflatoxins
.O
Determinable aflatoxins, ng/mL
.o .o
.o .o .O .O
&AL,FL, GA, KY, LA, MS, NC, SC, TN. bIA, IL, IN, KS, MI, MN, MO, NE, OH, SD, WI. Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
No. of products
Percentage of products
Year
No. of products examined
> .5
> .5
1989 1990 1991
632 79 168
8 2 18
1.2 2.5 10.7
3946
WOOD
other selected commodities. Twelve states had no formal monitoring program but were equipped to respond to a n aflatoxin outbreak whenever the need arose. A number of these states have adopted the regulatory limits established by FDA and are actively participating with FDA in a n aflatoxin data exchange program.
Other Mycotoxins Many reports in the literature relate to the occurrence of mycotoxins other than aflatoxins in foods and feeds. A major concern is the accuracy of the data. Of the many analytical methods that have been published and used for obtaining survey data on mycotoxins, only a few have been subjected to formal interlaboratory study. In many cases, confirmation of analyte identity is not included. In view of the large variability associated with determining the mycotoxin concentrations in a given lot of food or feed and the limited numbers of samples analyzed, one must use caution in drawing conclusions about the quantitative results on mycotoxins reported in the literature. For the FDA to establish the need for a formal regulatory control program for a particular mycotoxin, background exposure data are needed as a first step. The following activities relating to other mycotoxins are also of concern to the FDA. Ochrufoxins. The ochratoxins are metabolites produced by certain species of the genera Aspergillus and Penicillium. Ochratoxin A is the major metabolite of toxicological significance and is mainly a contaminant of cereal grains (corn, barley, wheat, and oats). It has also been found in beans (soya, coffee, cocoa), peanuts, and meat in some countries (Krogh, 1987). The results from surveys of corn, wheat, barley, sorghum, and oats conducted by the USDA and FDA between 1967 and 1985 revealed a very low concentration of contamination. Less than 2% of the 2,313 samples examined contained ochratoxin A. (A. E. Pohland, personal communication). The incidence of contamination was highest in barley. No ochratoxin A was found in sorghum. Ochratoxin A is nephrotoxic, teratogenic, and hepatotoxic in certain animal species and is believed to be a causal factor of a particular form of nephropathy observed in humans in the Balkan countries (Bulgaria, Romania, and Yugoslavia; Prior et al., 1983; Krogh, 1987). Recent studies suggest that ochratoxin A is a renal and hepatic carcinogen in mice and rats (Kanizawa, 1984; Bendele et al., 1985; Boorman, 1988; Kuiper-Goodman and Scott, 1989). In view of the latter findings, the FDA initiated a survey in 1989 to determine the incidence and concentrations of ochratoxin A in selected processed products in the United States. The commodities examined included dried peas/ Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
beans, barley (whole/cereals), barley malt, green coffee beans, corn cereals, corn meal, oats (meal, crackers), rice (whole/cereals), rye flour, wheat flour, and soya-based baby food products. Of 351 samples collected and examined, none contained ochratoxin A. The limit of detection of the methodology used was approximately 10 ng/g. The results suggest that ochratoxin A contamination is not a major problem in the United States at this time. However, there is a need for continued surveillance. Zearalenone. Zearalenone is a nonsteroidal, estrogenic mycotoxin produced by Fusarium species. It is associated with reproductive problems in certain animals and possibly in humans. It is mainly a contaminant in corn. However, it may occur in oats, barley, wheat, and sorghum (Mirocha et al., 1976). Surveys for zearalenone in feeds (corn, corn products, wheat, soybean, sorghum) moving in commercial channels in the United States were conducted by the FDA and USDA over a 9-yr period (Bennett and Shotwell, 1979). The results revealed that only 8% of the 1,722 samples examined contained measurable concentrations of the toxin. The incidence and concentrations in corn varied from year to year, depending on the prevailing weather conditions that influenced the planting and harvesting time for a particular area. In two recent surveys of processed grain-based products breakfast cereals, popcorn, snack foods, corn meal, crackers/cookies/muffin mixes) conducted during 1985 and 1989, the same relative concentrations of zearalenone (average 19 to 20 pg/g) were detected each year, despite the adverse weather conditions that prevailed only during the 1989 crop year (Warner and Pestka, 1987; Abouzied et al., 1991). In vivo studies have revealed that zearalenone is rapidly metabolized in animals and humans and eliminated mainly as water-soluble glucuronides (Mirocha et al., 1981).Free and conjugated forms of zearalenone have been found in the milk of lactating cows under experimental conditions (Mirocha et al., 1981). That high oral doses of the toxin are required to elicit such a response indicates that consumption of contaminated feed by dairy cows would not result in a health hazard to humans (Prelusky et al., 1990). An assessment of the health risks associated with the presence of zearalenone in food products in Canada was recently published (Kuiper-Goodman et al., 1987). Tnchothecenes. At least 148 trichothecenes have been isolated and identified, mainly from Fusarium species (Scott, 1990). Deoxynivalenol (DON; vomitoxin), produced by F. graminearurn, is among the most frequent trichothecene contaminants found on cereal crops in the United States. Wheat and corn are particularly affected. Contamination
MYCOTOXINS IN FOODS AND FEEDS of these crops by F. graminearurn usually occurs when harvest is immediately preceded by cool and wet weather conditions (Pathre and Mirocha, 1979). Zearalenone is commonly found to co-occur with DON in the United States. Adverse weather conditions in the central part of the United States during the 1982 crop year resulted in a n unusually high incidence of infection of winter wheat by Fusaria. Surveys of mold-damaged wheat for DON were conducted by the FDA and USDA (Eppley et al., 1984; Shotwell et al., 1985). The data reflected high concentrations (average 3.6 pg/g) of DON in the scabby wheat as well as a good correlation between the occurrence of DON and the degree of scabbiness (grade) of the wheat. Shelled corn collected at various grading stations within the major corn-growing region was examined and found to contain up to 2.14 pg of DON/g (average .35 pg/gl. The FDA issued a n “advisory” to federal and state officials recommending a level of concern for DON of 2 pg of DON/g for wheat entering the milling process, 1 pg/g in finished wheat products for human consumption, and 4 pg/g for wheat and wheat milling by-products used in animal feed (Anonymous, 19821. To assess the potential for human exposure to DON in finished wheat and corn-based products in commercial channels, several surveys were conducted (Brumley et al., 1985; Trucksess et al., 1985; Wood and Carter, 1989; Abouzied et al., 1991). High incidences of DON contamination were reported for various wheat and corn products, including snack foods, breakfast cereals, and oat- and rice-based products. The mean concentration of DON in all positive samples in the most recent survey was > 4 pg/g (Abouzied et al., 1991). Based on current toxicological data, the highest concentration of DON found in the surveys ( > 10 pg/g for two samples) would not present a n acute toxicity risk to humans (Forsell et al., 1987; Ueno, 1987). Deoxynivalenol is rapidly metabolized in all animal species studied. Therefore, residues of DON would not be expected to accumulate in edible tissues to a n extent that would pose a health hazard to humans (Prelusky et al., 1984; Prelusky and Trenholm, 1991). The T-2toxin, produced mainly by Fusarium tricinctum, was the first trichothecene to be found as a naturally occurring grain contaminant in the United States (Hsu et al., 1972). It was associated with a lethal toxicosis in dairy cattle that had consumed moldy corn in Wisconsin. No other confirmed incidence of T-2 toxin has been reported in the United States. This toxin is rarely a s sociated with disorders in animals or humans in other countries (Mirocha, 1984). The chance of finding it as a residue in edible tissue is remote Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
3947
because it is rapidly metabolized in vivo (Yoshizawa et al., 1981). There are no confirmed reports of the occurrence of nivalenol in the United States. The cooccurrence of nivalenol with DON in cereal grains in Canada, Japan, and other countries has been well documented (Scott, 1990). PatuZin and PeniciZlic Acid. Patulin is a toxic metabolite of several fungal genera, including Penicillia. The natural occurrence of patulin has been associated with soft rot in apples and other fruits. If the fruit contains sulfhydryl compounds in a n amount sufficient to bind all patulin produced, it will not be a problem (Scott and Somers, 1968). In view of its instability in foods rich in sulfhydryl compounds (grains, meats, and cheese) and its low oral toxicity in animals studied, patulin does not seem to be of real concern in the United States (Becci et al., 1981; Harrison, 1989). Penicillic acid is also produced by species of Penicillia. This toxin has been found in “blue eye” corn and dried beans (Thorpe and Johnson, 1974). Limited reports on the occurrence of penicillic acid in foods may be attributed to its property of reacting with sulfhydryl compounds in a manner similar to that of patulin. Citn’nin. Citrinin, produced by species of the genera Penicillia, is usually found in feedstuff as a co-contaminant with ochratoxin. Citrinin is a nephrotoxin, like ochratoxin A, and causes lesions in many animal species and, specifically, renal tumors in rats (Arai and Hibino, 1983). Unfortunately, no satisfactory analytical methods are available for this mycotoxin. Therefore, incidences and concentrations reported in foods and feeds are not reliable. There are no confirmed reports of the occurrence of citrinin in the United States. CycZopiazonic Acid. Cyclopiazonic acid (CPAI is produced by several Penicillia species and by A. flavus. It has been found naturally in corn, cheese, and visibly molded peanuts (Gallagher et al., 1978; LeBars, 1979; Lansden and Davidson, 1983). Because analytical methods for CPA are not well developed, there are no survey data relating to incidence and concentrations in susceptible commodities. The acute toxicity of CPA is low in the animal species studied, and there are no chronic toxicity data currently available (Norred, 1990). Sterigmatocystin. Sterigmatocystin is produced by several species of the genus Aspergillus and by other fungal genera. It is of concern because its structure is very similar to that of aflatoxin and it also exhibits carcinogenic and mutagenic properties (Purchase and van der Watt, 1973; Ueno et al., 19781. Although the genera that produce this toxin are widely distributed among agricultural commodities, there are very few reports on the natural
3948
WOOD
occurrence of this toxin (Schroeder and Hein, 1977; Northolt et al., 1980). In a survey conducted by the FDA during 1974 and 1975, no sterigmatocystin was found in any of 574 grain samples examined (Stoloff, 1982). Alternaria. Fungi of the genus Alternaria are commonly found in the soil and are frequently encountered on agricultural products after harvest. The major mycotoxins produced by species of this genus include alternariol, alternariol methyl ether, altenuene, altertoxin-1, and tenuazonic acid. In the United States, some of these mycotoxins have been found in damaged grains and nuts and in infected fruits and vegetables (Seitz et al., 1975; Schroeder and Cole, 1977; Stinson et al., 1981; Stack et al., 1985). Because current survey (incidence/concentrations) and toxicological data are insufficient, the hazards associated with these toxins in foods and feeds cannot be assessed. Ergot Alkaloids. The ergot alkaloids are found in the sclerotia formed by Claviceps purpura and other fungal species on cereal grains. These alkaloids are responsible for the human disease ergotism, which is rarely reported today. The enforcement of grading standards and the cleaning, milling, and thermal processes used for cereal grains have greatly reduced the concentration of these alkaloids present in commercial products (Scott and Lawrence, 1982). In the United States, ergot alkaloids are believed to be responsible for the toxicity of tall fescue grass to cattle (Lyons et al., 19861. Fumonisins.The Fumonisins (FB1 and FB$ were recently isolated from Fusarium moniliforme cultures and found to promote cancer in rats (Gelderblom et al., 1988). These toxins occur naturally in corn and have been associated with equine leukoencephalomalacia and porcine pulmonary edema syndrome in the United States (Ross et al., 1990; Wilson et al., 19901. Although several analytical methods have been published, only one has been subjected to a collaborative study, and the results of that study have not yet been published. An intragovernmental research committee was recently formed (FDA-USDN to oversee the status of developing research. Its aim is to identify and support research for regulatory needs, to aid in development of analytical methods (including rapid screening tests), and to encourage additional government and private funding for fumonisin research.
Implications The surveillance and regulatory programs of the Food and Drug Administration for mycotoxins are designed to keep the amount in foods and Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
feeds a t the lowest concentrations attainable and are consistent with maintaining a n adequate commodity supply at a reasonable cost. Human exposure to aflatoxins in the United States is relatively low. The monitoring efforts of the Food and Drug Administration are complemented by control programs carried out by USDA, state departments of agriculture, and various trade associations. Data on incidences and concentrations of various mycotoxins in the United States can be coupled with toxicological data so that estimates of human risks can be made and regulatory limits imposed when warranted.
Literature Cited Abouzied, M. M., J. I. Azcona, W. E. Braselton, and J. J. Pestka. 1991. Immunochemical assessment of mycotoxins in 1989 grain foods: Evidence for deoxynivalenol (vomitoxid c o n tamination. Appl. Environ. Microbiol. 57372. Anonymous. 1982. Food Chem. News 24:3. AOAC. 1990. Official Methods of Analysis (15th Ed.). Association of Official Analytical Chemists, Arlington, VA. Arai, M., and T. Hibino. 1983. Tumorigenicity of citrinin in male F344 rats. Cancer Lett. 7:281. Becci, P. J., F. G. Hess, W. D. Johnson, M. A. Gallo, J. G. Bobish, R. E. Dailey, and R. A. Parent. 1981. Long-term carcinogenicity and toxicity studies of patulin in rats. J. Appl. Tox icol. 1:256. Bendele, A. M., W. W. Carlton, P. Krogh, and E. B. Lillehoj. 1985. Ochratoxin A carcinogenesis in the (C57BL/BJXC 3H) F1 mouse. J. Natl. Cancer Inst. 75:733. Bennett, G. A., and 0. L. Shotwell. 1979. Zearalenone in cereal grains. J. Am. Oil Chem. SOC.56:812. Boorman, G. 1988. NTP Technical report on the toxicology and carcinogenesis studies of ochratoxin A (CAS No. 303.47-9)in F344/N rats (gavage studies), NIH Publ. No. 89-2813. US. Dept. of Health and Human Services, National Institutes of Health, Research Triangle Park, NC. Brumley, W. C., M. W. Trucksess, S. H. Adler, C. K. Cohen, K. D. White, and J. A. Sphon. 1985. Negative ion chemical ionization mass spectrometry of deoxynivalenol (DON):Application to identification of DON in grains and snack foods after quantitation/isolation by thin layer chromatography. J. Agric. Food Chem. 33:326. Eppley, R.M., M. W. Trucksess, S.Nesheim, C. W. Thorpe, G. E. Wood, and A. E. Pohland. 1984. Deoxynivalenol in winter wheat: Thin layer chromatographic method and survey. J. Assoc. Off. Anal. Chem. 67:43. FDA. 1988. Action levels for added poisonous or deleterious substances in food. Fed. Regist. 53:5043. Forsell, J. H., R. Jensen, J. H. Tai, M. Witt, W. S. Lin, and J. J. Pestka. 1987. Comparison of acute toxicities of deox ynivalenol (vomitoxinl and 15-acetyldeoxynivalenol in the BBCBFl mouse. Food Chem. Toxicol. 25:155. Gallagher, R.T., J. L. Richard, H. M. Stahr, and R. J. Cole. 1978. Cyclopiazonic acid production by aflatoxigenic and Aspergillus pavus. nonaflatoxigenic strains of Mycopathologia 66:31. Gelderblom, W.C.A.,K. Jaskiewicz, W.F.O. Marasas, P. G. Thiel, R. M. Horak, R. Vleggaar, and N.P.J. Kriek. 1988. Fumonisins-novel mycotoxins with cancer-promoting activity produced by Fusarium monilifome. Appl. Environ. Microbiol. 54:1806. Harrison, M. A. 1989. Presence and stability of patulin in apple products: A review. J. Food Saf. 9:147.
MYCOTOXINS IN FOODS AND FEEDS Hsu, 1.H.-C.,E. B. Smalley, F. M. Strong, and W. E. Ribelin. 1972. Identification of T-2toxin in moldy corn associated with a lethal toxicosis in dairy cattle. Appl. Microbiol. 24:684. Jelinek, C. F., A. E. Pohland, and G.E. Wood. 1989. Worldwide occurrence of mycotoxins in foods and feeds-an update. J. Assoc. Off. Anal. Chem. 72:223. Kanizawa, M. 1984. Synergistic effect of citrinin on hepatorenal carcinogenesis of OA in mice. In: H. Kurata and Y. Ueno (Ed.) Toxigenic Fungi-Their Toxins and Health Hazard. p 245. Elsevier, Amsterdam. Krogh, P. 1987. Ochratoxins in food. I n P. Krogh (Ed.)Mycotox ins in Food. p 97. Academic Press, London. Kuiper-Goodman, T., and P. M. Scott. 1989. Risk assessment of the mycotoxin ochratoxin A. Biomed. Environ. Sci. 2:179. Kuiper-Goodman, T., P. M. Scott and H. Watanabe. 1987. Risk assessment of the mycotoxin zearalenone. Reg. Toxicol. Pharmacol. 7:253. Lansden, J. A., and J. I. Davidson. 1983. Occurrence of cyclopiazonic acid in peanuts. Appl. Environ. Microbol. 45:766. LeBars, J. 1979. Cyclopiazonic acid production by Penicillium camemberti Thorn and natural occurrence of this mycotoxin in cheese. Appl. Environ. Microbiol. 38:1052. Lyons, P. C., R. D. Plattner, and C. W. Bacon. 1986. Occurrence of peptide and clavine ergot alkaloids in tall fescue grass. Science 232:487. Mirocha, C. J. 1984. Mycotoxicoses associated with Fusarium. In: M. 0. Moss and J. E. Smith [Ed.) The Applied Mycology of Fusarium. p 141. Cambridge University Press, U.K. Mirocha, C. J., S. V. Pathre, andT. S.Robison. 1981. Comparative metabolism of zearalenone and transmission into bovine milk. Food Cosmet. Toxicol. 19:25. Mirocha, C. J., S. V. Pathre, B. Schauerhamer, and C. M. Christensen. 1976. Natural occurrence of Fusarium toxin in feedstuff. Appl. Environ. Microbiol. 32:553. Norred, W. P. 1990. Cyclopiazonic acid: toxicity and tissue distribution. Vet. Hum. Toxicol. 32(Suppl.):20. Northolt, M. D., H. P. van Egmond, P. Soentoro, and E. Deijll. 1980. Fungal growth and presence of sterigmatocystin in hard cheese. J. Assoc. Off. Anal. Chem. 63:115. Park, D. L., and A. E. Pohland. 1989. Sampling and sample preparation for detection and quantitation of natural toxicants in food and feed. J. Assoc. Off.Anal. Chem. 72:399. Pathre, S. V., and C. J. Mirocha. 1979. Trichothecenes: natural occurrence and potential hazard. J. Am. Oil Chem. SOC.56: 820.
Pohland, A. E., and G. E. Wood. 1990. Natural occurrence of mycotoxins. I n G.A. Bray and D. H. Ryan (Ed.) Mycotox. ins, Cancer and Health. Pennington Center Nutritional Series, Vol. 1. Louisiana State University Press, Baton Rouge. Prelusky, D. B., P. M. Scott, H. L. Trenholm, and G. A. Lawrence. 1990. Minimal transmission of zearalenone to milk of dairy cows. 3. Environ. Sci. Health B25:87. Perlusky, D. B., and H. L. Trenholm. 1991. Tissue distribution of deoxynivalenol in swine dosed intravenously. J. Agric. Food Chem. 39:748. Prelusky, D. B., H. L. Trenholm, G. A. Lawrence, and P. M. Scott. 1984. Nontransmission of deoxynivalenol (vomitoxin) to milk following oral administration to dairy cows. J. Environ. Sci. Health B19:593. Prior, M. G., C. S. Sisodia, and F. Hrudka. 1983. Some cellular effects of ochratoxin A. Toxicon 3(Suppl.l:353. Purchase, I.F.H., and J. J. van der Watt. 1973. Carcinogenicity of sterigmatocystin to rat skin. Toxicol. Appl. Pharmacol. 26: 274.
Ross,P. F., P. E. Nelson, J. L. Richard, G. D. Osweiler, L. G. Rice, R. D. Plattner, and T. M. Wilson. 1990. Production of fumonisins by Fusarium monilifonne and Fusarium prolifeeraturn isolates associated with equine leukoen-
Downloaded from https://academic.oup.com/jas/article-abstract/70/12/3941/4632085 by University of Wyoming Libraries user on 19 June 2018
3949
cephalomalacia and a pulmonary edema syndrome in swine. Appl. Environ. Microbiol. 56:3225. Schroeder, H. W., and R. J. Cole. 1977. Natural occurrence of alternariols in discolored pecans. J. Agric. Food Chem. 25: 204.
Schroeder, H. W., and H. Hein. 1977. Natural occurrence of sterigmatocystin in in-shell pecans. Can. J. Microbiol. 23: 639.
Scott, P. M. 1984. Effects of processing on mycotoxins. J. Food h o t . 41:489. Scott, P. M. 1990. Trichothecenes in grains. Cereal Foods World 35:661.
Scott, P. M., and G. A. Lawrence. 1982. Losses of ergot alkaloids during making of bread and pancakes. J. Agric. Food Chem. 30:445. Scott, P. M.. and E. Somers. 1968. Stability of patulin and penicillic acid in fruit juices and flour. J. Agric. Food Chem. 16:483.
Seitz, L. M., D. B. Sauer, H. E. Mohr, and R. Burroughs. 1975. Weathered grain sorghum: Natural occurrence of alternariols and storability of the grain. Phytopathology 65:1259. Shotwell, 0. L., G.A. Bennett, R. D. Stubblefield, G. M. Shannon, W. F. Kwolek, and E. D. Plattner. 1965. Deoxynivalenol in hard red wheat: Relationship between toxin levels and grading factors. J. Assoc. Off. Anal. Chem. 88:954. Stack, M. E., P. B. Mislivec, J.A.G. Roach, and A. E. Pohland. 1985. Liquid chromatographic determination of tenuazonic acid and alternariol methyl ether in tomatoes and tomato products. J. Assoc. Off. Anal. Chem. 68:640. Stinson, E. E., D. F. Osman, E. G. Heisler, J. Siciliand, and D. D. Bills. 1981. Mycotoxin production in whole tomatoes, a p ples, oranges and lemons. J. Agric. Food Chem. 29:790. Stoloff, L. 1982. Mycotoxins as potential environmental carcinogens. I n H. F. Stich (Ed.)Carcinogens and Mutagens in the Environment. Val. 1. p 88. CRC Press, Boca Raton. FL. Thorpe, C. W., and R. L. Johnson. 1974. Analysis of penicillic acid by gas-liquid chromatography. J. Assoc. Off. Anal. Chem. 57:861. Trucksess, M. W., G. E. Wood, R. M. Eppley, K. Young, C. K. Cohen, S. W. Page, and A. E. Pohland. 1985. Occurrence of deoxynivalenol in grain and grain products. Biodeterioration 6:243. Ueno, Y. 1987. Trichothecenes in food. In: P. Krogh (Ed.) Mycotoxins in Food. p 123. Academic Press, London. Ueno, Y., K. Kubota, T. Ito, and Y. Nakamura. 1978. Mutagenicity of carcinogenic mycotoxins in Salmonella typhimurium. Cancer Res. 38538. van Egmond, H. P. 1989. Current situation on regulations for mycotoxins. Overview of tolerances and status of standard methods of sampling and analysis. Food Addit. Contam. 6: 139.
Warner, R. L., and J. J. Pestka. 1987. ELISA survey of retail grain-based food products for zearalenone and aflatoxin B1. J. Food Prot. 50:502. Wilson, T. M., P. F. Ross, L. G. Rice, G. D. Osweiler, H. A. Nelson, D. L. Owens, R. D. Plattner, C. Reggiardo, T. H. Noon, and J. W. Pickrell. 1890. Fumonisin B1 levels associated with an epizootic of equine leukoencephalomalacia. J. Vet. Diagn. Invest. 2:213. Wood, G. E., and L. Carter. 1989. Limited survey of deoxynivalenol in wheat and corn in the United States. J. Assoc. Off. Anal. Chem. 72:38. Yoshizawa, T., C. J. Mirocha, J. C. Behrens, and S. P. Swanson. 1981. Metabolic fate of T-2 toxin in a lactating cow. Food Cosmet. Toxicol. 19:31.
