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L Stoloff

Publications and source records attributed to L Stoloff.

At least 19 recordsLinked to original sources

An analysis of the 1987 list of IARC-identified human carcinogens and the correlated animal studies.

The thesis that the use of long-term, appropriately conducted and interpreted laboratory studies with rats and/or mice to test materials for potential carcinogenicity in humans is supported by the evidence on human carcinogens developed by Working Groups of the International Agency for Research on Cancer (IARC) is examined by a review of the Working Group reports on IARC-designated human carcinogens. The conclusion from that review is that the list of carcinogens does not constitute a sufficiently diverse group of agents to warrant a generalization; nor do the correlated animal studies justify the implied claim that most human carcinogens are demonstrated animal carcinogens, when the test for animal carcinogenicity is a properly conducted and interpreted study with rats and/or mice.

Animals

Aflatoxin control--how a regulatory agency managed risk from an unavoidable natural toxicant in food and feed.

The control by the Food and Drug Administration (FDA) of aflatoxin, a relatively recently discovered, unavoidable natural contaminant produced by specific molds that invade a number of basic food and feedstuffs, provides an example of the varying forces that affect risk assessment and management by a regulatory Agency. This is the story of how the FDA responded to the initial discovery of a potential carcinogenic hazard to humans in a domestic commodity, to the developing information concerning the nature of the hazard, to the economic and political pressures that are created by the impact of natural forces on regulatory controls, and to the restraints of laws within which the Agency must work. This story covers four periods: the years of discovery and action decisions on the basis of meager knowledge and the fear of cancer; the years of tinkering on paper with the regulatory process, the years of digestion of the accumulating knowledge, and the application of that knowledge to actions forced by natural events; and an audit of the current status of knowledge about the hazard from aflatoxin, and proposals for regulatory control based on that knowledge.

Aflatoxins

Aflatoxin is not a probably human carcinogen: the published evidence is sufficient.

Since the early 1960s, when aflatoxin, the mold-produced contaminant of a number of important food commodities, was found to be a potent hepatocarcinogen for laboratory rats, there has been a sustained search for evidence to support the regulatory presumption that aflatoxin is a probable human carcinogen. The developing laboratory evidence of differences between species in metabolism of aflatoxin and susceptibility to its oncogenic effects indicated that humans were probably refractory to aflatoxin carcinogenesis, but the early epidemiological evidence indicated otherwise. That epidemiological evidence, however, contained flaws so that Working Groups of the International Agency for Research on Cancer (IARC) meeting in 1970, 1976, and 1982, although ignoring the biochemical evidence, did consider the available epidemiological evidence insufficient for a conclusion of human carcinogenicity. During the 1970s and 1980s, studies on the connection between chronic infection with hepatitis B virus (HBV) and primary liver cell cancer (PLC), the expected lesion from aflatoxin exposure, had established a very strong etiological relationship between HBV and PLC. Since all the epidemiological studies of aflatoxin and PLC conducted prior to 1982 had been of populations with endemic HBV infection, and, in addition to other flaws, had not been controlled for this confounding factor, there was a solid basis for their rejection. Most epidemiological studies in the 1980s of aflatoxin and PLC were either in the United States, where HBV-infected groups could be excluded from the study, or, when in areas of chronic HBV infection, attempts were made to include that factor. The study of U.S. populations showed no difference in mortality rates from PLC that could be attributed to aflatoxin exposure. The studies of populations with endemic HBV infection produced no convincing evidence to support a primary role for aflatoxin in the induction of human PLC, although an accessory role to HBV infection for aflatoxin could not be ruled out. However, the epidemiological studies of the HBV/PLC relation indicate that an accessory factor is not an essential condition, a conclusion supported by animal models and a laboratory study that specifically found no interaction between aflatoxin and a hepatitis virus in the duck, a species in which liver cancer can be induced by either agent. It was surprising that an IARC Working Group meeting in 1987 concluded, on the basis of much of this evidence that was available at that time, and citing other studies that appear to be irrelevant to the issue, that there was sufficient evidence to consider aflatoxin a probable human carcinogen.

Aflatoxins

Distribution of aflatoxins B1 and M1 in contaminated calf and pig livers.

The determination of aflatoxins B1 and M1 in multiple sections of livers from 4 calves and 1 pig exposed to high levels of aflatoxins showed a uniform distribution of the aflatoxins in each liver, within the precision of the analytical method used. The thin layer chromatographic method has an expected within-laboratory coefficient of variation of 15%.

Aflatoxins

Extraction, cleanup, and quantitative determination of aflatoxins B1 ANd M1 in beef liver.

A method for the determination of aflatoxin B1 in eggs was applicable for aflatoxin B1 in liver, but ineffective for aflatoxin M1 in liver because of poor recovery of added aflatoxin and interferences in thin layer chromatography. The method was modified by the addition of citric acid to the extracting solvent and ammonium sulfate to the extract solution for removing protein. The elution system for silica gel column cleanup was also changed by substituting methanol for acetone, and adding a step for confirmation of aflatoxin M1 identity. The method has been used successfully for survey and research on aflatoxin residues in animal tissues.

Aflatoxins

Matthew.

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Deafness

Survey for aflatoxin B1 in chicken eggs.

Samples of egg products were obtained during January and July 1977 from 35 establishments located in the southern part of the United States. Of the 112 samples analyzed, aflatoxin B1 was found in 1 sample of liquid egg white at a level of 0.06 ng/g. No aflatoxin was found in 101 samples of shell eggs offered for sale to consumers in Alabama, Georgia, South Carolina, and North Carolina in the late fall of 1977.

Aflatoxins

Aflatoxin and zearalenone occurrence in dry-milled corn products.

Eighty-two corn dry-milling establishments in 20 states were surveyed concerning control practices for preventing the use of corn contaminated with aflatoxin or zearalenone. Prime products and by-products from each establishment were analyzed for these mycotoxins to determine whether a correlation exists between control practices and product contamination. No zearalenone was detected in any product; there was little awareness of the potential for contamination with this mycotoxin. No correlation was found between control practices and aflatoxin contamination encountered, but there was a positive correlation between aflatoxin contamination and the geographical source of the corn. Reported experimental findings in regard to the distribution of aflatoxin between prime product and by-product were generally corroborated.

Aflatoxins

Thin layer chromatographic determination of aflatoxin B1 in eggs.

A method for determining aflatoxin in dairy products was modified for eggs, initially by additional cleanup steps. The modified method proved practical for use in survey analyses and was sufficiently sensitive to detect aflatoxin B1 at levels less than 1 ng/g in eggs from hens on experimentally contaminated feed and in spiked eggs; interfering compounds in eggs received from many different producing areas were eliminated. Although recovery was greater than 75% when the aflatoxin was extracted immediately after spiking, recovery was usually less than 30% when the aflatoxin was extracted after more than 24 hr. Adding sodium chloride, sodium sulfate, or urea to the extracting solvent remedied this defect, which is thought to be related to the binding of aflatoxin to egg protein.

Aflatoxins

Survey for aflatoxins and zearalenone in 1973 crop corn stored on farms and in country elevators.

A total of 315 marketable and 57 obviously damaged corn samples were collected at 116 different farms and country elevators located in the United States in countries selected from among those producing more than 1 million bushels of corn in 1972. The samples were analyzed for aflatoxins and zearalenone. The most striking correlations observed were between geographical area and mycotoxin contamination. Aflatoxin contamination was most frequently encountered in the Southeast-Appalachia areas with a 44% incidence of marketable corn with detectable aflatoxins. Zearalenone was most frequently encountered in the Corn Belt with 10% incidence in marketable corn from that region. When mycotoxin contamination was found in an establishment, most of the samples from that establishment were contaminated. There was no correlation between mycotoxin contamination and storage practices nor could the observed contamination of marketable corn be related to the contamination of the obviously damaged grain. These observations plus correlations with the geographic incidence and aflatoxin level distribution of published field contamination data suggest the possibility of a common contamination mode.

Aflatoxins

A review of sampling plans and collaboratively studied methods of analysis for aflatoxins.

Aflatoxins are the only food contaminants being monitored routinely on an international scale with methods operating at the order of magnitude of 10 mug/kg. At this concentration level, methods of analysis which can achieve coefficients of variation of 30-40% with recoveries of 70% or greater in interlaboratory collaborative studies can be considered eligible for referee status. In most cases, sample reproducibility is the variable limiting the reliability of methods of analysis. The inherent uncertainty of the identity of chromatographically separated entities requires the application of confirmatory tests to verify that the characteristic measured results from the presence of aflatoxin. The methods are also inoperable without a verification of the identity, purity, and concentration of the reference standards used. Screening methods which reliably eliminate negative samples from further consideration are indispensible for the practical operation of monitoring programs.

Aflatoxins

Stability of aflatoxin M in milk.

This three-part study was designed to determine aflatoxin M recovery from pasteurized and/or stored cow's milk. (a) Aflatoxin M was added to samples of raw Holstein milk at a concentration of 2.0 mug/liter. Half of each sample then was pasteurized at 63 C for 30 min, and both raw and pasteurized portions were stored at 4 C up to 17 days. (b) Samples of raw milk, pasteurized (77 C, 16 s) skim milk, dry cottage cheese curd, and cottage cheese whey were taken from a commercial operation in an area in which natural contamination had been encountered. (c) Milk from a cow dosed with aflatoxin B1 was stored frozen (-18 C) in bulk and in assay-size sample containers for 120 days. Aflatoxin M was recovered completely after either storage or pasteurization in (a) and (b). In (c), a recovery deficiency was detectable after 68 days of storage, which increased to 45% of the original value by 120 days. These observations differ from those of others in that loss of aflatoxin M was significant after pasteurization or storage of raw milk, totaling 87% loss after 120 days of frozen storage. Aflatoxin M partitioning between curd and whey in the preparation of cottage cheese agrees with more recent studies, but differs from previous reports. Three possible explanations for the differences are offered.

Aflatoxins