Gossypol toxicosis in a dog consequent to ingestion of cottonseed bedding.

Six dogs died after accidental ingestion of cottonseed bedding. No clinical signs of illness were observed prior to death. A full diagnostic workup was performed on one of these dogs. At necropsy, the lungs were congested and edematous, and the liver was firm, congested, and had a marked reticular pattern. There was also moderate ascites. Histopathologic examination revealed multifocal myocardial degeneration and necrosis, severe pulmonary edema, and chronic passive congestion of the lungs, heart, liver, and kidneys. Transmission electron microscopy of the myocardium revealed disruption of myofibrils, chromatin condensation, and disrupted and swollen mitochondria. The cottonseed bedding contained 1,600 mg/kg of free gossypol, a concentration considered toxic for monogastric animals. The stomach content revealed the presence of gossypol, thus confirming ingestion of cottonseed. Gossypol poisoning in dogs is extremely rare and has not yet been associated with cottonseed bedding. This first documented case of gossypol poisoning in a dog, caused by the ingestion of cottonseed bedding, demonstrates how specific toxicological analysis is crucial in reaching an accurate diagnosis.

Pathological lesions in lambs fed raw or processed cottonseed meal.

Thirty male lambs of 3-4 months of age, were assigned equally to five dietary treatments in a completely randomized design and fed isonitrogenous and isocaloric concentrate mixtures containing 30% de-oiled peanut meal (DPNM) or 40%, cottonseed meal, which was raw, cooked for 45 min or treated with either 1%, calcium hydroxide or iron (1:3, free gossypol: Fe). The mixtures containing raw or variously processed CSM replaced about 50% of the nitrogen of the reference concentrate mixture. These concentrate mixtures were fed to meet 80% of the animals' crude protein requirements along with ad libitum feeding of maize (Zea mays) hay for 180 days. The free gossypol content of the raw cottonseed meal (0.27%) was reduced to 0.16% 0.20% and 0.21% by the cooking, Ca(OH)2 and iron treatments, respectively. At the end of the experiment, the tissues of various organs were fixed in 10% formol saline. embedded in paraffin and sectioned at 4-5 microm thickness, and duplicate sections were stained with either haematoxylin and eosin or Perl's Prussian blue. The lambs fed diets incorporating raw, cooked, Ca(OH)2- or iron-treated cottonseed meal consumed respectively 302, 215, 250 and 222 mg free gossypol/day. No morbidity. mortality or gross lesions were observed in any organs and the histopathological lesions due to cottonseed meal were limited to the testes and epididymis. Spermatogonial cells were absent in the majority of the seminiferous tubules of testes from lambs fed raw cottonseed meal. Most seminiferous tubules were collapsed, with a reduced wall thickness, owing to there being fewer germ cell layers and vacuolation of the basal cells. The epithelium of the epididymal ductules was degenerated, desquamated to a variable degree with hyperplastic changes, and they were devoid of spermatozoa. Most lambs fed any of the processed cottonseed meals did not show any of these lesions, and such lesions as occurred in affected lambs in these groups were relatively mild. Iron pigments were deposited around the portal areas of the liver, the tip of intestinal villi and the spleen of lambs fed the iron-treated cottonseed meal diet. Cooking or treatment with 1%, Ca(OH)2 effectively minimized the toxic effects of free gossypol.

Gossypol toxicity in preruminant calves.

Twenty-four of 57 calves fed a diet containing 33% cotton seed meal (CSM) died between 7 and 15 weeks of age. Initial deaths were not accompanied by premonitory signs, but after CSM withdrawal most calves developed rough coats, anorexia, weakness, ascites and subcutaneous oedema. Those that died had large volumes of serous fluid in the body cavities, hard livers of 'nutmeg' appearance, and pulmonary congestion. Histopathologically the livers showed periacinar necrosis in acute cases and periacinar fibrosis in chronic cases. Lungs from several calves had oedema, haemosiderosis and fibrosis in some pulmonary vessels. Atrophy of myocardial fibres was present in most cases. The concentration of free gossypol in the diet was 100 to 220 mg/kg. Ante-mortem and post-mortem findings supported a diagnosis of gossypol poisoning. The deaths continued for 4 weeks after withdrawal of CSM from the diet.

Apparent gossypol-induced toxicosis in adult dairy goats.

Consumption of a cotton-seed meal-based mineral supplement (cattle label) and a concentrate dairy mix (goat label) resulted in gossypol toxicosis in 3 adult dairy goats. The primary clinical signs were limb swelling and stiffness, ventral abdominal edema, and anorexia. All does died within a few days of the onset of illness. Necropsy revealed generalized subcutaneous edema, acute centrilobular necrosis of the liver, and myocardial fibrosis, consistent with a diagnosis of gossypol toxicosis. It was estimated that the does had consumed from 348 to 414 mg of free gossypol/d for at least 3 months. Apparent gossypol toxicosis in goats consuming this amount of free gossypol indicates that goats may be more susceptible than cattle to this substance.

Effects of gossypol and cottonseed products on reproduction of mammals.

Gossypol is a toxic factor indigenous to the cotton plant genus Gossypium. Concentrations of free gossypol contained in feedstuffs such as whole cottonseed and cottonseed meals vary considerably. Nonruminant animals are particularly sensitive to the toxic effects of gossypol, whereas ruminants are somewhat more resistant. Signs of gossypol toxicosis in nonruminants, preruminants, and ruminants are similar and include labored breathing, dyspnea, decreased growth rate, and anorexia but are not pathognomonic. Postmortem findings include generalized edema and congestion of lungs and liver, fluid-filled thoracic and peritoneal cavities, and degeneration of heart fibers. The antifertility effect observed in many nonruminant species is overshadowed by toxic effects, particularly in females. Gossypol seems to disrupt estrous cycles, pregnancy, and early embryo development in females of all nonruminant species studied. Probable mechanisms include an endocrine effect on the ovary as well as a cytotoxic effect on the uterus or embryo. The female ruminant seems to be relatively insensitive to the antifertility effect of gossypol; however, in vitro data indicate some inhibition of embryonic development and ovarian steroidogenesis. The antifertility effect of gossypol has been studied most in males of nonruminant species. The effects of gossypol in the male are both dose- and time-dependent. At effective doses, gossypol causes males to be infertile because of sperm immotility and depressed sperm counts. Specific mitochondrial damage in the tails of spermatozoa seems to render them immotile, and extensive damage to germinal epithelium may be responsible for depressions in spermatogenesis. In ruminant males fed diets containing gossypol, ejaculated sperm appears normal under light microscopy. The integrity of the membrane of sperm cells may be damaged. Extensive damage to the germinal epithelium has been shown in both rams and bulls fed diets containing gossypol and is of major concern.

A review of toxicity factors in some food and feedingstuffs in the nutrition of man and livestock in Nigeria.

A review of the toxicity factors in some food and feedingstuffs in the nutrition of man and livestock in Nigeria was conducted. The crops reviewed were cassava, cocoyam, guinea corn, cottonseed, soyabean, bambara, groundnut and cowpea. These crops provide cheap sources of carbohydrate and protein in the diets of humans and livestock. However, antinutritional factors inhibit their use. Antinutritional or toxic factors associated with them are reviewed and means of detoxifying them for human and livestock feeding are enumerated.

Incidence and management of poisonings in livestock.

Insecticides, nitrates, gossypol, copper, and plants are a few of the common toxicoses observed in livestock in a particular specie due to various factors. Some species may have anatomical or physiological uniquenesses making them more susceptible to certain agents. Another specie may be exposed to some agents more frequently than others, increasing the likelihood of toxicosis in that specie. Once recognized, therapy is often unrewarding due to the advanced stage of the condition when first recognized, the stress involved in administering the treatment, and the unfeasibility of multiple treatments on many animals. Because of the poor response to treatment and the large number of animals potentially at risk, prevention assumes a greater importance in food animals than in companion animals. Prevention consists of making the diagnosis, findings and removing the source of the toxicant, and educating the owner on how future problems can be avoided.

Cottonseed meal (gossypol) toxicosis in a swine herd.

Cottonseed meal (CSM) that contained a high concentration of free gossypol was inadvertently used as a protein supplement, without appropriate iron supplementation, for a swine herd in Illinois. Fifty percent of 300 grower and finishing swine died, and an additional 20% became ill during a 4- to 6-week period. Clinical signs included respiratory distress and abdominal distention. At necropsy, the hearts were diffusely pale, flaccid, and rounded because of dilatation of all 4 chambers, the livers were large and congested, and hydropericardium, hydrothorax, and ascites were evident. Histologic changes consisted of diffuse myocardial fiber atropy with perinuclear vacuolation, and multifocal myocardial and skeletal muscle necrosis. Changes in the liver included marked centrilobular congestion, loss of hepatocytes, and fatty degeneration. Differential diagnoses included monensin, selenium, and gossypol toxicoses, and vitamin E/selenium deficiency. Analyzed feed samples did not contain monensin. Feed selenium concentrations ranged from 428 to 1,513 micrograms/kg, and iron concentrations from 160 to 180 mg/kg. Cottonseed meal (3 to 10%) was detected by feed microscopy. A sample of the 40% protein supplement contained 19% CSM and 1,300 mg of free gossypol/kg, whereas feed samples contained 200 to 400 mg of free gossypol/kg. The history, clinical signs, pathologic findings, and feed analyses were compatible with a diagnosis of gossypol toxicosis. Cottonseed meal, a high-protein supplement used widely in southern United States, may contain gossypol (a polyphenolic binaphthalene pigment), which in its free form is especially toxic to simple-stomached animals. If CSM is used, supplementation with ferrous sulfate is recommended at a 1:1 weight ratio with free gossypol, up to 400 mg of FeSO4/kg.

Gossypol as a toxicant in livestock.

Many cases of gossypol toxicity have been misdiagnosed. The long-held belief that gossypol toxicity did not occur in ruminants has been a major hurdle to overcome. Field necropsies in which pulmonary congestion and edema were attributed to shipping-fever pneumonia, failure to examine the heart either grossly or microscopically, failure to believe that 200 ppm free gossypol could kill a calf, failure to believe that any age of sheep could suffer gossypol toxicity, and failure to believe that just because you fed the same thing last year, it will not cause a problem this year, all were factors in causing the misdiagnosis of this toxicity. Gossypol toxicity cases diagnosed will increase each year because of increased awareness among veterinarians. Continued research will help to increase our understanding of this multifactored toxin and, possibly, devise ways to detoxify it before it is utilized in a feed. Until then, it will have to be considered because it will continue to be present as a potential toxicant in the feed.

Gossypol toxicosis in a herd of beef calves.

A 6-month-old crossbred calf was examined as representative of a herd of calves experiencing dyspnea and death, with few other clinical signs of illness. Physical examination of the calf identified pleural and peritoneal effusion and poor body condition. The calf did not respond to supportive treatment, and necropsy of it and another calf from the herd identified congestive heart failure as the cause of death. Gossypol toxicosis was the cause of congestive heart failure in this herd; the source of the toxin was a cottonseed meal and cottonseed hull ration fed by the owner.

Pathological and toxicological studies of calves fed a high concentration cotton seed meal diet.

Feeding a high concentration of cotton seed meal to young calves resulted in death with lesions compatible with gossypol toxicity. Calves were fed two different commercially prepared rations. Free gossypol concentrations in different lots of the 17% protein ration varied from 250 to 380 ppm, and the 13% protein ration varied from 40 to 240 ppm. Serum sorbitol dehydrogenase elevation was the most consistent clinical pathological finding. The mean serum sorbitol dehydrogenase concentrations for moribund, hospitalized, and clinically healthy calves were 277, 34, and 45 units/liter. The mean for sorbitol dehydrogenase concentration for healthy calves not fed cotton seed meal was 18 units/liter. Gross lesions included severe effusion of a high protein content fluid into the body cavities of most calves, edema of the mesentery, and hepatomegaly. The most consistent histological lesion was severe centrilobular hepatic necrosis. Elevated levels of liver gossypol were demonstrated. The mean liver gossypol concentration for three calves was 41.7 micrograms/g on a wet weight basis.

A perspective on gossypol ingestion in swine.

Cottonseed meal has been used for many years as a protein supplement in animal rations. Due to a polyphenol pigment, gossypol, present in cottonseed meal, its use for swine has been limited. The tolerance of gossypol for monogastric animals depends upon age and species with older animals being less sensitive than younger animals. Swine are highly susceptible to gossypol poisoning, and signs commonly develop after one or more months of consumption. The use of iron salts in the ration appears to be antidotal, and lysine supplementation of gossypol containing diets appears to improve gain. Reproductive performance can also be affected, including reduced conception and litter size. New extraction methodologies are being developed to reduce the amount of gossypol in cottonseed meal.

Heart failure caused by gossypol poisoning in two dogs.

Two hound-type dogs from the same kennel were admitted in terminal stages of congestive heart failure. An investigation revealed the owner had been feeding the dogs cottonseed meal daily with their kibbled meal. Gossypol toxicosis from feeding this meal caused marked abnormalities in myocardial contractility. Although in severe congestive heart failure, one dog had only minimal dilatation of its heart, as revealed by thoracic radiography. Disseminated intravascular coagulopathy also was diagnosed in this dog. Gossypol is a cumulative toxin; the amount of free gossypol fed was approximately 5.4 to 5.7 mg/kg/day for an unknown duration.