Environmental fate of trifluralin.

Trifluralin, a preemergence, soil-applied and soil-incorporated herbicide, has been in agricultural use since 1963. The environmental chemistry and fate of dinitroaniline herbicides, including trifluralin, has been studied extensively in agricultural soils. Probst et al. (1975) and Helling (1976) have summarized pre-1975 data on the mobility, persistence, and degradation or metabolism of dinitroaniline herbicides as a group. Since then, numerous studies have been carried out on the fate of dinitroanilines, especially trifluralin, in the environment to understand further their degradation in soil, potential for mobility and persistence, and environmental concentration in water and air. The present review, while summarizing briefly earlier data, concentrates primarily on the post-1975 data on degradation, mobility, and persistence of trifluralin in soils and its potential concentrations in water and air. Trifluralin is readily degraded under sunlight in all media, with half-lives (t1/2) of minutes to several months, depending on the substrate. In addition, other dissipation processes, such as microbial and chemical, are also operative in soils, water, and sediments. Several degradation products of trifluralin have been identified and characterized, both under photolysis and following aerobic and anaerobic metabolism in soils and water-sediment systems. The differences between various degradative pathways of trifluralin appear to be more quantitative than qualitative in nature, leading eventually to the same end products that are subject to binding or mineralization with time. The general lack of accumulation of the breakdown products of trifluralin suggests that these are also subject to the same degradative mechanisms as the parent compound. Trifluralin has low water solubility and is strongly bound to soil components; mean Koc values range from 4,000 to 13,000. Once applied and incorporated into the soil, trifluralin remains relatively immobile with minimal or no potential for contamination of groundwaters under or near the treated zones. Trifluralin residues in soil surface layers are subject to loss via transport in runoff water or volatilization into the air. Seasonal losses in surface runoff are consistently less than 0.5% of the amounts applied, with concentrations in edge-of-the-field run-off water typically < 1.0 microgram L-1. Consequently, trifluralin is infrequently detected in surface waters and, if present, usually occurs below levels of quantification. Seasonal trifluralin losses into the atmosphere can be as high as 25% of that applied. Maximum trifluralin residues in the air above treated fields are in the 2-3 micrograms m-3 range following application, decreasing to < 100 ng m-3 in ambient air of intensive use areas, indicating its rapid dissipation in air. Trifluralin residues at < 100 pg m-3 in the atmosphere of remote nonuse regions have been reported, suggesting its potential for long-range transport. However, there is a general lack of understanding of the mechanisms controlling its potential for long-distance transport, especially considering its rapid photodegradation in vapor and solution states. The persistence of trifluralin in agricultural soils following incorporation is highly variable, depending on several factors such as depth of incorporation, soil moisture, soil temperature, soil air, and soil organic matter content. Estimated half-lives under a variety of agronomic conditions range from 25 to > 201 d, thus categorizing its persistence from 'moderate' to 'persistent'. The estimated half-life data for trifluralin under agronomic conditions, however, cannot be extrapolated to other potential scenarios, such as its dissipation in nontarget areas where trifluralin residues, if any, are essentially deposited on surfaces. Surface deposits on nontarget areas, unlike soil-incorporated residues, would be subject to volatilization and photolysis and thus more short lived. (ABSTRACT TRUNCATED)

A cluster-focus of multiple sclerosis at Henribourg, Saskatchewan.

This study presents the clinical characteristics of 8 victims of multiple sclerosis from the hamlet of Henribourg, Saskatchewan with a population of less than 75 people. A diligent victim of the disease had observed that six female classmates from the early 1940's had later developed multiple sclerosis. Two male military personnel who had also resided briefly in close proximity, during the same common exposure time, also later developed multiple sclerosis. The mean onset time of developing the disease after leaving the area was 20 years. This cluster-focus suggests a common exposure to an environmental factor or a common infective agent in the etiology of multiple sclerosis.

Synergistic effects of T-2 toxin and a low protein diet on erythropoiesis in mice.

Young male Swiss mice fed on a semipurified diet containing 8% protein and 10 ppm of T-2 toxin developed erythroid hypoplasia within 2 weeks. Red blood cell counts declined to 36% of control values by 6 weeks but had risen to 45% of control values by 8 weeks. Between 4 and 8 weeks, erythropoietic tissues regenerated and reticulocyte counts became greatly elevated. The toxin-free semipurified diet was adequate for normal growth and did not cause anemia in control mice fed either ad lib, or at a restricted rate. Anemia did not occur in mice fed the 10-ppm level to T-2 toxin in either a semipurified diet containing 16% protein, or in a balanced natural-ingredient mouse diet. These observations demonstrated that the inhibitory effect of T-2 toxin in erythropoiesis in mice was transient, and depended on the nutritional composition of the diet.

A method for accurate measurement of cutaneous irritancy of trichothecenes.

Conventional skin irritation bioassays for trichothecenes are semiquantitative because test animals vary in sensitivity, and the intensity of cutaneous inflammation is poorly correlated with dose. A quantitative bioassay was therefore devised for toxicological studies on the irritancy of trichothecenes. A graded series of six standard solutions of T-2 toxin (10-60 micrograms/mL) in 2 microL volumes was applied to the shaved skin of young female Wistar rats. Each test sample was applied at least twice to each of five rats. After 48 hours, reactions were rated in units of equivalent concentrations of T-2 toxin, so that measurements were independent of the intensity of inflammatory reaction. Mean concentrations of replicate measurements of test solutions of T-2 toxin between 10 and 60 micrograms/mL were precise (SEM less than 1.6 micrograms/mL) and accurate (within 13% of actual concentrations).

Effects of low-level long-term oral exposure to T-2 toxin in CD-1 mice.

In a 16-month feeding study male and female CD-1 mice received semi-synthetic diets containing 0, 1.5 or 3.0 ppm T-2 toxin. Feed consumption, body-weight gains, clinical findings (including haematological examinations at 16 months) and the development of external lesions were recorded. At 3, 6, 12 and 16 months, animals were killed for assessment of their immune function. Disease-related deaths did not differ among groups. Histological examination of all organs revealed statistically significant differences from controls in the incidence of pulmonary adenomas and hepatic adenomas in the 3.0-ppm group. Other treatment-related findings were an increased prevalence of epithelial hyperplasia in the forestomach of animals treated with T-2 toxin, and increased heart weights in treated male mice. T-lymphocyte-dependent humoral immunity tests did not reveal treatment effects and haematology revealed no particular trends. It is concluded that chronic feeding of T-2 toxin at low levels is not immunosuppressive but has a carcinogenic or tumour-promoting effect in mice.

Geotoxicology of multiple sclerosis: the Henribourg, Saskatchewan, cluster focus. II. The soil.

The childhood-related, geographically-linked factor which predisposes towards (or protects against) multiple sclerosis (MS) could be one or more chemicals in the environment. Chemical study of the environment or "focus" of an MS cluster may maximize the chances of detecting such an etiological link. The soil chemistry of an MS focus (Henribourg, Saskatchewan) was compared with North American norms, and with the chemistry of soil from a nearby control area with a near-zero incidence of MS and of childhood homes of MS cases. A combination of our present results with those reported in the literature suggests that an environment predisposing to MS may have a number of the following chemical characteristics: Calcareous; with soils (but not necessarily waters) generally low in copper, iron and vanadium; with excess lead, nickel and zinc in the upper soil layer; with waters relatively high in chloride, chromium, molybdenum, nitrate plus nitrite, and zinc; but low in selenium and sulfate. One possible causal pathway to explain the apparent link between the excess rate of MS and some of the curious geochemical findings at Henribourg is presented. Many other possible explanations could equally well be advanced, and methods for testing such alternative hypotheses are proposed.

Geotoxicology of multiple sclerosis: the Henribourg, Saskatchewan, Cluster Focus. I. The water.

Some childhood-related, geographically-linked factor predisposes towards (or protects against) multiple sclerosis (MS). It is quite plausible that this factor could be one or more chemicals in the environment, and that chemical study of the environment or "focus" of an MS cluster might maximize the chances of detecting such an etiological link. The water chemistry of such a focus (Henribourg, Saskatchewan) was compared with North American norms, and with the chemistry of water from a nearby control area with a near-zero incidence of MS and of childhood homes of MS cases. Overall, the results suggest that an environment predisposing to MS may have a number of water chemistry characteristics such as: relative deficiency of selenium and sulfate, but relative abundance of barium, calcium, chloride, chromium, magnesium, manganese, molybdenum, nitrate plus nitrite, strontium and zinc. Possible explanations for the apparent link between the excess rate of MS and the water geochemistry findings at Henribourg are discussed.

Differentiation of lesions caused by mycotoxin T-2 from autolytic morphologic change in CD-1 mice.

Experiments with topically applied T-2 trichothecene mycotoxin were undertaken to determine whether lesions caused by this toxin could be differentiated from autolysis. Two pathologists, who had previously seen lesions caused by T-2 toxin, graded lesions without knowledge of treatment group and stated whether the animal had received the toxin or not. Both pathologists differentiated T-2 toxin-treated mice up to 6 h post-mortem. Failure to distinguish between treated and control mice resulted in false-negative diagnoses only. It was concluded that the diagnosis of trichothecene mycotoxicosis would probably be missed more than 6 h post-mortem.

Equine colitis "X", still an enigma?

Colitis "X" is a sporadic diarrheal disease of horses with clinical signs of dehydration, electrolyte imbalances and "shock"-like features. Macroscopic and microscopic findings include signs of disseminated intravascular coagulation, necrosis of colonic mucosa and presence of large numbers of bacteria in the devitalized parts of the intestine. Recently published work suggests that the causative agent may be Clostridium perfringens, Type A, but the bacteria are recoverable only in the preliminary stages of the disease. Excess protein and lack of cellulose content in the diet is thought to be the trigger for the multiplication of the clostridial organisms. The pathological findings are pathognomonic, but clinically, a number of differential diagnoses have to be considered, such as intestinal accidents, salmonellosis, heavy metal intoxication and occlusive verminous arteritis.

Alleged mycotoxicosis in swine: review of a court case.

Vomition and diarrhea in feeder pigs, and signs of hyperestrogenism in sows and pregnant gilts in a large swine operation were thought to be caused by mycotoxins. Various toxicoanalytical tests performed were negative and the cause of the disease was never clearly established. On the basis of the Sale of Goods legislation, a court ruled that the company supplying the feed was responsible for the losses that occurred. The veterinary and legal aspects of the case are reviewed, and it is concluded that there is a need for reliable and readily available laboratory diagnosis of toxins in feedstuff. The importance of gathering whatever evidence is available and of conducting whatever tests are capable of being conducted, is stressed.

Chronic copper toxicity in a dairy herd.

The addition of excessive copper to a commercially prepared dairy ration caused chronic copper toxicity in a dairy herd. A formulation error by a feed company resulted in copper levels of 800 to 1,000 mg/kg in the "as fed concentrate," amounting to about 400-500 mg copper/kg of the whole ration. Five animals died with typical signs of acute copper toxicity, including intravascular hemolysis and methemoglobinemia. A further 39 cows died on the farm from a combination of debilitation and secondary infectious causes, and 215 were sent to slaughter because of debilitation and poor milk production. The mortality of calves born to dams that had been fed the toxic concentrate was approximately 50%.We postulate that dairy cows, particularly pregnant cows, may be more susceptible to copper toxicity than other cattle, and suggest reexamination of the presently allowable maximum levels of copper supplementation of diets for dairy cattle.

Chronic copper toxicity in a dairy cow.

A three year old Holstein dairy cow fed a ration containing a copper supplement died of chronic copper poisoning. The concentration of copper in the liver was 331 ppm (wet weight). The typical lesions of chronic copper toxicity including icterus, hepatic fibrosis and hemoglobinemic nephrosis were found at necropsy. The chronic copper toxicity was not considered to be a herd problem since the liver copper concentration in a slaughtered cull animal and blood samples taken from five animals in the same herd were within normal limits.

Mycotoxicoses of domestic animals and their diagnosis.

Mycotoxins have been named "agents in search of a disease," and the considerable progress in analytical methodology over the last 10 years has not changed this very much. The following are factors that contribute to the difficulty of making a diagnosis: (1) nonspecificity of lesions; (2) masking of mycotoxic effects by secondary effects, e.g., through immunosuppression; (3) late appearance of a lesion, e.g., bone marrow damage or neoplasia; (4) interaction of several mycotoxins or presence of other toxicants or deficiency states; (5) species variation in the response to the mycotoxin(s); (6) difficulty of linking a late appearing effect with a demonstrable cause; (7) low doses of mycotoxins may cause stimulating effects; and (8) not being aware of the potential of a mycotoxin as a causative factor in disease. The mycotoxins of major importance in Canada are trichothecenes, ochratoxin, zearalenone, and ergot. It is concluded that the significance of mycotoxins for animals in Canada is likely generally underestimated.

Maternal toxicity, embryolethality and abnormal fetal development in CD-1 mice following one oral dose of T-2 toxin.

An experiment was undertaken to determine the teratogenic effect of oral administration of T-2 toxin, a trichothecene mycotoxin. Firstly, a dose response study using 0, 0.5, 1.0, 2.0, 3.0, 3.5 and 4.0 mg/kg T-2 toxin in propylene glycol, on day 9 of pregnancy, was undertaken. Maternal deaths and toxicity was noted in the 4.0 and 3.5 mg/kg groups post-toxin administration. These groups gained less weight throughout gestation than the rest of the groups, because no fetuses were found in the 4.0 mg/kg group and the 3.5 mg/kg group had significantly fewer fetuses than the remaining groups. The total fetal weight was similar among all groups with fetuses, and normal sex ratio of offspring was seen. More major and minor defects were seen in the 3.0 mg/kg T-2 toxin treated group than any other group. Secondly, a day response trial using a single dose of 3.0 mg/kg T-2 toxin given on either days 6, 7, 8, 10, 11 or 12 of gestation was undertaken. Maternal mortality, with placental hemorrhage, was observed. Fetal loss was greater in the T-2 toxin treated groups than in the starved controls. The greatest number of dead term fetuses was seen in mice treated on day 9 of gestation. Normal sex ratios were present in the offspring. Major skeletal defects were more numerous in mice treated on day 7 of gestation, whereas minor defects, retardations and variants were more common in mice treated on day 8. It was concluded that a single oral dose of T-2 toxin in propylene glycol is primarily maternotoxic and embryolethal, and that defective development was possibly secondary to maternal toxicity.

Experimental transmission of a feline mycobacterial skin disease (feline leprosy).

Non-culturable acid-fast bacteria from two spontaneous cases of so-called feline leprosy were transmitted to rats and cats and further passaged in rats or cats. Two to six months after infection, cats developed cutaneous lesions that were indistinguishable from spontaneous cases, including the occurrence of nasal granulomata in one cat. When injected into rats, the mycobacteria caused a generalized mycobacteriosis and the granulomatous reaction was composed chiefly of macrophages without polymorphonuclear granulocytes. Infection of cats with Mycobacterium lepraemurium did not produce any lesions. The feline disease may be a suitable model for the study of human leprosy (Hansen's Disease).

Subacute toxicity of Dietary T-2 toxin in mice: influence of protein nutrition.

The subacute toxic effects of dietary T-2 toxin (20 ppm) incorporated in semipurified diets of 8%, 12% or 16% protein, were examined in young Swiss mice after one, two, three and four weeks. Dietary T-2 toxin caused substantial reductions in growth and food consumptaion, the degrees of which were greatest in mice fed the diets of reduced protein content. T-2 toxin consistently caused similar degrees of nonregenerative anemia, lymphopenia, thymic atrophy and gastric hyperkeratosis irrespective of the dietary protein level. However, erythroid hypoplasia was temporary in mice fed T-2 toxin in the 16%-protein diet such that erythroid precursors regenerated in splenic and bone marrow and were hyperplastic after four weeks. Liver to body weight ratios of mice fed T-2 toxin in the 16%-and 12%-protein diets increased during the four week trial in comparison to control mice fed at a similar rate. These observations indicated that suppression of erythropoiesis in mice by dietary T-2 toxin was temporarty and that the interval before regeneration was prolonged by diets of reduced protein content.

Comparative toxicity of dietary T-2 toxin in rats and mice.

The subacute toxic effects of dietary T-2 toxin were compared in young male Wistar rats, young male Swiss mice and juvenile Swiss mice. Purified T-2 toxin was fed in the diet at levels of 10 or 20 ppm for 2 or 4 weeks. Dose-related depressions in food consumption and weight gain consistently occurred in all animals fed T-2 toxin. Hyperkeratosis of the squamous gastric mucosa, atrophy of the thymus and thymus-dependent lymphoid tissues, and lymphopenia occurred in all animals exposed to T-2 toxin. These effects were most severe in juvenile mice, and least severe in rats. In addition, juvenile mice fed the 20-ppm level developed erythroid hypoplasia and became severely anemic by 4 weeks. These results demonstrate that dietary T-2 toxin at levels up to 20 ppm cause similar effects attributable to food refusal and alimentary irritation in both species. However, mice and rats were relatively resistant to hematopoietic suppression. Only the juvenile mice fed 20 ppm developed this potentially lethal toxic effect.

Potential consequences of a fire in an insecticide storage facility.

Assumptions are identified and made in an attempt to model the acute human health risk associated with a hypothetical fire in an insecticide storage facility. The insecticides used in the model are endrin and dimethoate. The model indicates that persons residing a few hundred meters from the facility could suffer a variety of adverse effects, including possible death from contact with smoke from a prolonged, low-temperature fire. Knowledge of the special hazards of cool toxic smoke as well as current atmospheric conditions could be of use to fire fighters. That is, fire fighters might wisely choose to promote a fast, hot fire which would propel toxicants high into the atmosphere rather than risk local fumigation.

Systemic effects of topical application of T-2 toxin in mice.

Topical application of T-2 toxin in dimethyl sulfoxide (DMSO) resulted in the death of 20/20 mice in the 20-, 30-, and 40-mg/kg body weight (BW) dose groups within 4 to 6 days after application, whereas 17/20 and 5/20 animals died in the 10- and 5 mg/kg BW groups, respectively, within 7 days. Histological examination of thymus, spleen, and duodenum at 6, 12, 18, and 24 hr after topical application of 5 or 40 mg/kg BW to mice revealed that the characteristic radiomimetic effects of this trichothecene mycotoxin are easily recognizable at 6 hr after topical application, with the severity of damage being dependent on the organ and time. The lesions are quantitatively and qualitatively identical with those seen after intragastrical application of T-2 toxin. Both the postmortem and, to some extent, the general histological findings were not specific enough to arrive at an etiological diagnosis without prior knowledge of the fact that a mycotoxin was applied to the skin, unless one had the opportunity to look for the characteristic intestinal lesions prior to 24 hr after application, or for necrosis in spleen an thymus after 24 hr.

Toxicology of novel macrocyclic trichothecenes, baccharinoid B4, myrotoxin B, and roritoxin B.

Baccharinoid B4, Myrotoxin B and Roritoxin B, some recently identified macrocyclic trichothecenes, were tested in Swiss mice with respect to their toxicity after oral and topical application. For oral dosing, the mycotoxins were dissolved in propylene glycol, and doses from 0 to 8.0 mg/kg body weight (BW) were employed. For topical application, toxins were dissolved in DMSO. A dose of 40 mg/kg BW was applied, except for Roritoxin B, where a dose of 10 mg/kg BW was also utilized. Animals were observed until death, or until 14 days after application and histopathological examinations were performed. It was found that Baccharinoid B4 was only moderately toxic, but this macrocyclic trichothecene appeared to exert its toxicity particularly on the intestine. Myrotoxin B was found to be quite toxic, and Roritoxin B was determined to be the most potent and toxic macrocyclic trichothecene of the three investigated. Oral administration of Roritoxin B resulted in death of 70-90% of mice at doses up to 1.0 mg/kg BW, and topical application of 10 or 40 mg/kg BW caused 100% death within 18 hours after application.