Gossypol as undesirable substance in animal feed Scientific Opinion of the Panel on Contaminants in the Food Chain

Gossypol is a yellow compound produced by the cotton plant that confers resistance to pests. Gossypol exists in two enantiomeric forms, (+) and (-), and is experimentally often used as a racemate, (+/-)-gossypol, or complexed with acetic acid. (+/-)-Gossypol is found in cottonseed and cottonseed products in two forms: free gossypol, which is readily extractable with solvents, and bound gossypol. The latter form represents mostly covalent adducts of gossypol to proteins, from which free gossypol can be (partially) liberated by heating with acids. Cottonseeds are by-products of cotton fibre production, and are rich in oil and proteins and are therefore used for cottonseed oil production and as a feed supplement. Storage, steam and heat, and extrusion of oil, reduce free gossypol concentrations and commercial production of cottonseed meals is now achieved routinely with only 0.1-0.2 % remaining as free gossypol. Gossypol shows moderate acute toxicity in most species with oral LD50s of 2400-3340 mg/kg for rats, 500-950 mg/kg for mice, 350-600 mg/kg for rabbits, 550 mg/kg for pigs and 280-300 mg/kg for guinea pigs. Signs of acute gossypol toxicity are similar in all animals and include dyspnoea and anorexia. Generally, (-)-gossypol is more biologically active than (+)gossypol. However, (+)-gossypol is more slowly eliminated. The main target organ of gossypol toxicity following repeated exposure to lower doses in rats and humans is the testis with reduced sperm motility, inhibited spermatogenesis and depressed sperm counts. Suppressed spermatogenesis in humans is partly irreversible, particularly in males with varicocele. Gossypol also affects female reproductive organs and embryo development. Gossypol is not genotoxic and it did not induce tumours in a one year study in rat. No healthbased guidance value (ADI, TDI) has been established for gossypol. The lowest oral doses inhibiting spermatogenesis in humans and monkeys were 0.1 and 0.35 mg/kg b.w., respectively. Gossypol is less toxic to ruminants, and inhibition of spermatogenesis, embryo development and increased erythrocyte fragility occur at doses of 6-18 mg/kg b. w. per day in cattle and cardiomyopathy in lambs at 2-3 mg/kg b.w. per day. Monogastric animals appear to be more susceptible to gossypol toxicity than ruminants. Current legislation includes maximum limits for free gossypol in both cottonseed meal and complete feedingstuffs. Under normal feeding practices, the concentration in complete feedingstuffs will be less than half the maximum permitted level, even assuming the highest permitted concentrations in cottonseed meal and maximum recommended inclusion rates of the meal in livestock diets. The concentrations of free gossypol that theoretically could be reached according to the current legislation on maximum permitted concentrations in complete feedingstuffs would lead to an intake of gossypol that could result in adverse effects in livestock. The potential exposure to free gossypol, based on the maximum permitted concentration in cottonseed meal and recommended maximum inclusion rates in complete feed, would not be expected to result in adverse effects in ruminants, poultry and fish. However, not all monogastric livestock animals, e.g. pigs, have been fully investigated for potential reproductive effects occurring at low doses in some species. There is a lack of data on gossypol content (free and bound) in feed materials used for livestock in the EU. However, information provided by the livestock feed industry indicates that amounts of cottonseed meal imported into the EU have declined significantly in recent years, and relatively little is now used as a feeding stuff for livestock in the EU. Industry sources confirm that it is not used as a feed for laying hens or fish. Gossypol is transferred to edible parts, muscle and offal of ruminants and poultry, and is probably transferred to cow's milk as it is transferred to breast milk in rats. There is very little quantitative information on transfer. At high experimental doses substantial amounts are transferred. No information was identified on the bioavailability of gossypol remaining in food products from animals fed gossypol containing feed. Human exposure to gossypol through the consumption of food products from animals fed gossypol seed derived products is probably low and would not result in adverse effects.