LEVAMISOLE

Levamisole is a broad-spectrum anthelmintic stimulating parasympathetic and sympathetic ganglia in susceptible mature gastrointestinal helminths and immature and mature lung worms. Approved use is in swine, sheep, horses, non-lactating dairy cattle and beef cattle. It is reported to be used in poultry for capillaria infections. USDA CES ranking is C-2 dated 1985. Withdrawal times for approved species range from two to nineteen days depending on formulation, species and dose. Data evaluated for the five year period from 1990-1994 indicates a low violation rate in bovine, ovine and swine slaughter classes. Not tested during this period were equine and avian species. Withdrawal from the 1998 NRP for species tested from 1990-1994 is recommended based on the low violation rate and low potential for human exposure represented by these samples. It is recommended that avian species be cycled into the program for evaluation of potential violation rates. Recycling of these compounds in a residue testing program should occur on a regular basis until a full risk assessment is completed that indicates no harm to human health from exposure at animal food tissue levels.

Doses for use of levamisole in poultry are available from numerous sources, though this is an unapproved use^1,2. No information is available from FARAD or FAO regarding the residue potential, either metabolism or withdrawal times, of levamisole use in poultry³. Usage data in poultry from the DOANES data is not available though the compound is inexpensive. Turkeys and poultry raised on range may be slaughter classes in which use of levamisole may occur and could be targeted for the 1998 program.

¹Plumb DC (1991). Veterinary Drug Handbook. Minneapolis: Pharma Vet Publishing, p. 382.

²FAO Food and Nutrition Paper (1994). Residues of Some Veterinary Drugs in Animals and Foods. Rome, February 1 - 10, 1994, 41:6, pp. 40-52.

³Sundlof SF, Riviere JE, Craigmill AL (1992). FARAD-The Food Animal Residue Avoidance Databank Trade Name File, Eighth Edition. University of Florida, pp. 193-200.

MYCOTOXINS

Mycotoxins include several classes of toxins that are discussed separately below. It is not recommended to include any of mycotoxins in the 1998 Residue Testing Program for the reasons listed for each class.

Fumonisins- Fumonisins are poorly absorbed from the gastro-intestinal tract of bovine species. Sources of information regarding other species are not available at this time. There are no established action levels for fumonisins in animal feeds and there is no regulatory information about conversion of concentrations in feed to concentrations in animal tissue as of 1993.

 Aflatoxins- The toxicity of aflatoxins varies greatly by species. Even when present in animal feeds, carryover ratios into tissues are very low (ranging from approximately 500:1 to 14,000+:1, excluding liver), particularly when compared to milk (70:1). Because of metabolism into hydrophillic moieties, the carryover ratios may be underestimated by approximately 35%. Production of aflatoxins in corn and grain is believed to be related to plant stress, brought on by insect infestation and drought. Additionally, certain storage conditions are believed to increase levels of aflatoxins.

In 1987, the International Agency for Research into Cancer (IARC) concluded that there was sufficient evidence to implicate aflatoxins as human carcinogens. Federal regulations restrict the movement and disposition of feedstuffs and feed ingredients that contain aflatoxin at levels greater than 20 ppm, except for cottonseed meal intended for beef cattle, swine, or poultry feed. For cottonseed meal, the tolerance is 300 ppm. Because of these restrictions and the low carryover rate, human exposure from animal food products is believed to be low. However, feedstuffs and feed ingredients that do not pass into inter-state commerce (direct on-farm usage and intra-state usage) are regulated by the states, not FDA. For that reason, little is known about the proportion of feed from these sources, and their potential for human exposure.

 Ochratoxins- Ochratoxins are well absorbed in non-ruminants, and often result in acute interstitial nephritis. Chronic exposure studies have led to ochratoxins being classified as both teratogens and carcinogens. There is little evidence that it occurs in the U.S. Carryover rates appear to be less variable than with aflatoxins, and blood levels in swine are a good indicator of tissue levels.

Mature ruminants have the ability to break down the toxin in their rumens, and are not particularly susceptible to ochratoxin poisoning, although non-ruminating calves that have not had "normal" microbiological exposures do not have the ability to metabolize ochratoxins.