Developmental toxicity of dietary zinc deficiency in New Zealand white rabbits

Chemically induced maternal Zn deficiency has been shown previously to cause terata and increase embryonic loss in rodents. To examine the potential effects of Zn deficiency in the rabbit, a major developmental toxicity test species, rabbit dams were fed an ethylenediamine-tetraacetic acid-washed alfalfa-based Zn-deficient diet (−Zn) or the same diet replete with 80 ppm Zn (control) from Gestation Day (GD) 0 through 20. A third group of animals was pair fed to match the mean daily feed consumption levels of the <2 ppm Zn group. By GD 7, maternal serum Zn levels of the − Zn dams were decreased 56% and reached a nadir with a 75% decrease of serum Zn by GD 14. Zinc concentrations in the visceral yolk sac and visceral yolk sac-exoceolomic fluid were decreased 30% and 50%, respectively, by GD 11. Although GD 11 embryonic Zn levels were not affected, the embryos from Zn-deficient dams exhibited decreased head length, somite number, and total protein. On GD 28, a significant increase in resorptions/litter was noted in the − Zn group, and the incidence of totally resorbed litters of the −Zn group was greater than laboratory historical control values. No terata were observed in GD 28 fetuses. This study indicates that Zn deficiency occurring during the standard dosing period of guideline rabbit developmental toxicity studies may be associated with a modest increase in resorption rate and a transient inhibition of embryonic growth, but in contrast to rodent species, does not appear to be teratogenic.     

Reproduction study in Japanese quail fed hexachlorobutadiene for 90 days

Adult male and female Japanese quail were fed diets containing 0.3, 3, 10, or 30 ppm of hexachlorobutadiene (HCBD) or 20 ppm of hexachlorobenzene (HCB) for 90 days. HCBD at all dose levels had no effect on body weight, demeanor, food consumption, egg production, the percent fertility and hatchability of eggs, the survival of hatched chicks, and egg-shell thickness. The birds showed no evident signs of toxicity during the study. In addition, there were no gross or histopathologic changes evident in the organs or tissues of birds at the termination of the study which could be related to treatment. Ingestion of a diet containing 20 ppm HCB resulted in decreased survival of chicks hatched during the study and an increase in the liver weight of adult birds at the end of the study. No other treatmentrelated changes were observed.     

Role of selenium toxicity and oxidative stress in aquatic birds

Adverse effects of selenium (Se) in wild aquatic birds have been documented as a consequence of pollution of the aquatic environment by subsurface agricultural drainwater and other sources. These effects include mortality, impaired reproduction with teratogenesis, reduced growth, histopathological lesions and alterations in hepatic glutathione metabolism. A review is provided, relating adverse biological effects of Se in aquatic birds to altered glutathione metabolism and oxidative stress. Laboratory studies, mainly with an organic form of Se, selenomethionine, have revealed oxidative stress in different stages of the mallard (Anas platyrhynchos) life cycle. As dietary and tissue concentrations of Se increase, increases in plasma and hepatic GSH peroxidase activities occur, followed by dose-dependent increases in the ratio of hepatic oxidized to reduced glutathione (GSSG:GSH) and ultimately hepatic lipid peroxidation measured as an increase in thiobarbituric acid reactive substances (TBARS). One or more of these oxidative effects were associated with teratogenesis (4.6 ppm wet weight Se in eggs), reduced growth in ducklings (15 ppm Se in liver), diminished immune function (5 ppm Se in liver) and histopathological lesions (29 ppm Se in liver) in adults. Manifestations of Se-related effects on glutathione metabolism were also apparent in field studies in seven species of aquatic birds. Reduced growth and possibly immune function but increased liver:body weight and hepatic GSSG:GSH ratios were apparent in american avocet (Recurvirostra americana) hatchlings from eggs containing 9 ppm Se. In black-necked stilts (Himantopus mexicanus), which contained somewhat lower Se concentrations, a decrease in hepatic GSH was apparent with few other effects. In adult American coots (Fulica americana), signs of Se toxicosis included emaciation, abnormal feather loss and histopathological lesions. Mean liver concentrations of 28 ppm Se (ww) in the coots were associated with elevated hepatic GSH peroxidase, depletion of hepatic protein bound thiols and total thiols, but a small increase in GSH. Diving ducks in the San Francisco Bay area exhibited a positive correlation between hepatic Se concentration and GSH peroxidase activity (r=0.63, P<0.05), but a negative correlation between hepatic Se and GSH concentration (r=-0.740, P<0.05). In willets (Catoptrophorus semipalmatus) from the San Diego area, positive correlations occurred between hepatic Se concentration and GSSG (r=0.70, P<0.001), GSSG:GSH ratio, and TBARS. In emperor geese (Chen canagica) from western Alaska, blood levels of up to 9.4 ppm occurred and were associated with increased plasma GSH peroxidase activity (r=0.62, P<0.001), but with decreased plasma GSSG reductase activity. When evaluating Se toxicity, interactive nutritional factors, including other elements and dietary protein, should also be taken into consideration. Further studies are needed to examine the relationship between different forms of environmentally occurring selenium, arsenic and mercury on reproduction, hepatotoxicity and immune function of aquatic birds. Further selenium nutritional interaction studies may also help to illucidate the mechanism of selenium induced teratogenesis, by optimizing GSH and other antioxidant defense mechanisms in a manner that would stabilize or raise the cell's threshold for susceptibility to toxic attack from excess selenium. It is concluded that Se-related manifestations of oxidative stress may serve as useful bioindicators of Se exposure and toxicity in wild aquatic birds.     

Distribution and biochemical effects of DDT, DDD and DDE in penned double-crested cormorants

Concentrations, distribution and chronic effects of DDT, DDD and DDE were determined in penned cormorants (Phalacrocorax a. auritus) treated with 2, 5 and 10 mg of a combination of these compounds daily in their diet. Birds stressed by a one-half decrease in food after the cessation of 9 weeks of treatment and birds that died of DDT toxicity showed a marked increase in brain and liver residues and a decrease in carcass residues. Higher brain residue levels were significantly correlated with decreased body weight (p < 0.01) and carcass lipid content (p < 0.05). DDD concentrations in the brain were found to be the best indicator of DDT toxicity. Brain concentrations ranged from 24 to 85 ppm in birds that died of toxic effects and from 0.4 to 29 ppm in survivors, indicating that 30 ppm was diagnostic of toxicity. Brain concentrations of DDT and metabolites in wild cormorants indicated no immediate danger of toxicity. Average residue levels in the carcass of wild adult cormorants was 1.00 ppm for DDD and 10.6 ppm for the total of DDT, DDD and DDE. This represents a total body burden of 2.2 mg of DDD and 23.3 mg of the DDT complex as adult cormorants averaged 2200 g in body weight. Analysis of total liver vitamin A indicated a significant decrease of vitamin A due to treatment. An analysis of variance showed a significant decrease in liver (p < 0.05) and heart weights (p < 0.05) due to treatment but not brain or spleen weights when analyzed as percentage of body weight. A significant negative correlation was found between liver weight and brain concentrations of DDE + DDD + DDT (p < 0.05). No significant effects due to treatment were found on blood chemistry values.     

Effects of dietary selenium on tissue concentrations, pathology, oxidative stress, and immune function in common eiders (Somateria mollissima)

Common eiders (Somateria mollissima) were fed added Se (as L-selenomethionine) in concentrations increasing from 10 to 80 ppm in a pilot study (Study 1) or 20 (low exposure) and up to 60 (high exposure) ppm Se in Study 2. Body weights of Study 1 ducks and high-exposure ducks in Study 2 declined rapidly. Mean concentrations of Se in blood reached 32.4 ppm wet weight in Study 1 and 17.5 ppm wet weight in high-exposure birds in Study 2. Mean Se concentrations in liver ranged from 351 (low exposure, Study 2) to 1252 ppm dry weight (Study 1). Oxidative stress was evidenced by Se-associated effects on glutathione metabolism. As Se concentrations in liver increased, Se-dependent glutathione peroxidase activity, glutathione reductase activity, oxidized glutathione levels, and the ratio of hepatic oxidized to reduced glutathione increased. In Study 2, the T-cell-mediated immune response was adversely affected in high-exposure eiders, but ducks in the low-exposure group exhibited evidence of an enhanced antibody-mediated immune response. Gross lesions in high-exposure ducks included emaciation, absence of thymus, and loss of nails from digits. Histologic lesions included severe depletion of lymphoid organs, hepatopathy, and necrosis of feather pulp and feather epithelium. Field studies showed that apparently healthy sea ducks generally have higher levels of Se in liver than healthy fresh-water birds, but lower than concentrations found in our study. Data indicate that common eiders and probably other sea ducks possess a higher threshold, or adverse effect level, for Se in tissues than fresh-water species. However, common eiders developed signs of Se toxicity similar to those seen in fresh-water birds.     

Measurement of the aquatic toxicity of volatile nitrosamines.

The acute toxicity of N-nitrosodimethylamine (DMN) and N-nitrosodiethylamine (DEN) was determined for three groups of aquatic organisms: algae, invertebrates, and fish. Toxicity of DMN and DEN to algae was assessed as a repression in the growth rate of either Selenastrum capricornutum or Anabaena flos-aquae in static bioassay tests. DMN and DEN concentrations of 1-10 ppm depressed algal growth in all cases. Invertebrate toxicity was determined in 96-h static bioassay tests with Dugesia dorotocephala and Gammarus limnaeus. The data indicated that these organisms are not highly susceptible to nitrosamine toxicity. The 96-h LC50s for D. dorotocephala were 1365 and 1490 ppm for DMN and DEN, respectively. Similar studies with G. limnaeus indicated LC50s of 330 and 500 ppm for DMN and DEN, respectively. Fish toxicity was also determined in 96-h statis bioassays with the fathead minnow (Pimephales promelas). Acute toxicities were calculated as LC50s of 940 and 775 ppm for DMN and DEN, respectively. Algae were calculated as LC50s of 940 and 775 ppm for DMN and DEN, respectively. Algae were quite sensitive to relative low levels of volatile nitrosamines, but higher organisms (invertebrates and fish) were relatively insensitive.     

Comparative effects of dietary parathion on the activities of cholinesterase and lecithin: Cholesterol acyltransferase in rat plasma

Adult female rats were fed either a control diet or diets containing parathion at varying concentrations for 11 days. Body weights and daily feed intake of animals administered parathion at levels less than 20 ppm were not modified during feeding trials by comparison with controls. Plasma cholinesterase activities were significantly reduced from control values for all dietary levels of the pesticide used (4–20 ppm). No significant alteration of the concentration of free cholesterol or lecithin:cholesterol acyltransferase activity in plasma was observed when parathion was fed. Plasma lecithin:cholesterol acyltransferase was judged to be a much less sensitive biochemical marker of in vivo parathion toxicity than plasma cholinesterase.     

A multi-generation toxicity evaluation of p,p'-DDT and dieldrin with Japanese quail. I. Effects on growth and reproduction

A toxicity Evaluation of DDT and dieldrin was conducted using Japanese Quail. The effects of feeding DDT (5 and 50 ppm of diet) and dieldrin (0.1 and 1.0 ppm of diet) in this four generation study (parental, F1, F2 and F3) were examined in terms of growth, viability, and/or reproduction of offspring. Ten groups (including controls and replicates of groups) contained 21 birds/group for the parental generation, and 21-35 chicks for each respective generation study. At 50 ppm DDT, a marginal decrease in egg hatch-ability of F2 generation was evidenced; the decrease appeared related to a slight decrease in fertility rather than egg production or hatchability of fertile eggs. Data accumulated from all other experimental groups were within the expected range and were comparable to control data.     

Effects of interactions between cadmium and zinc on phytochelatin and glutathione production in wheat (Triticum aestivum L.)

It has been proposed that phytochelatins (PCs) act as a biomarker for the evaluation of metal toxicity. Little attention has been paid to the effects on metal combinations and glutathione (GSH), the most abundant cellular thiol. In the present study the effects of interactions between cadmium (Cd) and zinc (Zn) on PC and GSH production were examined in wheat tissue over 14 days' exposure. The results showed that the presence of Zn alleviated Cd toxicity, accompanied by a reduction of Cd uptake. Cd and Zn exposure increased PC-SH levels in concentration-, tissue- and time-dependent manners. Of the two metals, Cd was more effective than Zn in PC-SH production. Interactions of Cd and Zn with respect to PC-SH production may be synergistic or inhibitory, strongly depending on duration of exposure and concentration of the metal combinations. Cd also stimulated GSH production in concentration-, tissue- and time-dependent manners, whereas Zn had no significant effects on GSH levels. Compared to the presence of Cd alone, the presence of Zn reduced GSH levels in a tissue-dependent manner over the growth period. The results of the study suggest that metal interactions should be highly considered in the application of PCs and GSH as potential biomarkers for the evaluation of metal toxicity, as most metal-polluted natural environments are contaminated with more than one metal.     

Subchronic Inhalation Toxicity Studies with Hydrochlorofluorocarbon 123 (HCFC 123)

Hydrochlorofluorocarbon 123 (HCFC 123) is one of the chemicalsbeing considered as a replacement for the chlorofluorocarbons.Four subchronic inhalation toxicity studies from 1 to 3 monthsin duration have been conducted with HCFC 123. One study utilizedrats and dogs, while the others were limited to rats only. Theexposure levels have ranged from 300 ppm up to 20,000 ppm. Althoughthe studies were conducted over a 14-year period, the resultswere consistent. In all studies, increases in liver weightswere seen at 1000 ppm and above; additionally, one showed thiseffect at 500 ppm. Histopathological findings were minimal,consisting primarily of focal necrosis in the liver of the dogsat 10,000 ppm. Induction of peroxisomal activity, lowering ofserum cholesterol and triglyceride levels, and an increase inurinary fluoride levels were also seen. The 4-hr LC₅₀ in therat has been reported as 35,000 ppm. At 20,000 ppm for 6 hr,the total daily dose on a concentration times time basis isalmost equal to the LC₅₀ yet, in the 4-week study, with 20 exposuresat this level, there was no mortality or even marked signs oftoxicity. There appeared to be no evidence for cumulative toxicityfrom multiple exposures in these studies. Overall, HCFC 123appears to have a low level of toxicity by the inhalation route.     

Effects of ingested 4000ppm aluminum on the essential metals, especially zinc, in intact and ethanol treated mice

The effects of ingested Al on the essential metals were investigated using mice. Animals were divided into 4 groups: 1) Control, 2) Al, 3) EtOH and 4) Al+EtOH groups. Powdered commercial food, containing 1.26% P, 1.36% Ca, 70ppm Zn, 15ppm Cu, 200ppm Fe and 3.1ppm Al, was used to prepare the diets. For Al-treated groups, Al(AlCl3) was added to powdered food at a concentration of 4000ppm. The co-existing effect of EtOH which is known to affect the essential metals, was also investigated as a possible modulater of Al toxicity at a concentration of 5% for 22 days, followed by 10% for 36 days in the drinking water. After 58 days feeding with food containing Al and / or EtOH containing water, the Al effects on serum and femur P and Ca were found to be slight except for a significant decrease of serum P concentration in the Al+EtOH group. In this group, femur weight was less and femur Al concentration was more compared with the Al group. The effects on Fe and Cu were little. We observed a significant decrease of serum Zn concentration with 4000ppm Al diet in both the Al-treated groups. The fact that serum ALPase activity, a Zn enzyme, increased in disregard of a significant decrease of serum Zn concentration suggested the enzyme release from injures tissues. It is noticeable that a significant decrease of serum Zn concentration was observed when dietary Zn was sufficient. It is reported that the dietary intake of Zn is under the recommended allowance for many people. Since Al compounds are widely used as drugs, food additives and a conditioned latent Zn deficiency is rather common in human diseases, the effects of Al on the Zn metabolism are to be investigated further.     

Effects of inhalation exposure to a binary mixture of benzene and toluene on vitamin a status and humoral and cell-mediated immunity in wild and captive American kestrels

Benzene and toluene are representative volatile organic compounds (VOC) released during production, storage, and transportation associated with the oil and gas industry and are chemicals of concern, as they are released in greater and possibly more biologically significant concentrations than other compounds. Most studies of air pollution in high oil and gas activity areas have neglected to consider risks to birds, including top-level predators. Birds can be used as highly sensitive monitors of air quality and since the avian respiratory tract is physiologically different from a rodent respiratory tract, effects of gases cannot be safely extrapolated from rodent studies. Wild and captive male American kestrels were exposed for approximately 1 h daily for 28 d to high (rodent lowest-observed-adverse-effect level [LOAEL] of 10 ppm and 80 ppm, respectively) or environmentally relevant (0.1 ppm and 0.8 ppm, respectively) levels of benzene and toluene. Altered immune responses characteristic of those seen in mammalian exposures were evident in kestrels. A decreased cell-mediated immunity, measured by delayed-type hypersensitivity testing, was evident in all exposed birds. There was no effect on humoral immunity. Plasma retinol levels as measured by high-performance liquid chromatography (HPLC) analysis were decreased in wild and captive kestrels exposed to the rodent LOAEL for combined benzene and toluene. This study indicates that American kestrels are sensitive to combined benzene and toluene. The study also illustrates the need for reference concentrations for airborne pollutants to be calculated, including sensitive endpoints specific to birds. Based on these findings, future studies need to include immune endpoints to determine the possible increased susceptibility of birds to inhaled toxicants.     

Comparative toxicity studies in birds using nimesulide and diclofenac sodium

Nimesulide, a sulfonanilide derivative, was compared with diclofenac sodium for toxicity in poultry. In this study, Vanaraja and PB1 birds of 6 weeks old (either sex) were mixed and equally divided into 5 groups of 10 birds each. The birds were inoculated with nimesulide, @ 5 and 2mg; vehicle @ 0.5ml; and diclofenac sodium @ 5mg on kg bwt basis. One group served as untreated control. All the groups were observed for a period of 28days. Forty percent mortality was observed within 12 days in diclofenac-treated group. While birds inoculated with nimesulide remained normal. No significant differences in the weight gain, haematology, total protein contents in the nimesulide and diclofenac groups (survived birds) were observed when compared with the control group of birds. Serum creatinine, cholesterol, alkaline phosphatase, and aspartate aminotransferase levels were significantly (P<0.05) high in diclofenac-treated group compared to nimesulide (P>0.05) and control groups. Nimesulide-treated groups did not show any histopathological lesions, where as diclofenac-treated birds showed histopathological lesions in liver and kidney.     

Effect of the antihypertensive drug hydralazine on mineral metabolism in the rat

The effects of hydralazine (HZ) on mineral metabolism was investigated in rats. Sprague-Dawley rats were fed HZ (0.1-4%, w/w) in three separate experiments: (1) a 2-week dose-response study; (2) a 2-month long-term feeding study; and (3) a pregnancy study. At the end of each experiment, tissues were removed and concentrations of Mn, Cu, Zn and Fe were measured. Results from the three experiments were similar. HZ had no effect on tissue Mn and Zn concentrations, while tissue Fe concentrations were lower and kidney Cu concentrations were higher in HZ-treated groups compared to controls. The effect of HZ on mineral metabolism may be, in part, responsible for some of its negative side effects.     

Weight-of-the-evidence review of acrylonitrile reproductive and developmental toxicity studies

Risk assessment of acrylonitrile (AN) toxicity to humans has focused on potential carcinogenicity and acute toxicity. Epidemiological studies from China reported reproductive and developmental effects in AN workers, including infertility, birth defects, and spontaneous abortions. A weight-of-the-evidence (WoE) evaluation of the AN database assessed study strength, characterized toxicity, and identified no-observed-adverse-effect levels (NOAELs). The epidemiological studies do not demonstrate causality and are not sufficiently robust to be used for risk assessment. Rodent developmental studies showed fetotoxicity and malformations at maternally toxic levels; there was no unique developmental susceptibility. NOAELs for oral and inhalation exposures were 10?mg/kg/day and 12?ppm (6?h/day), respectively. Drinking-water and inhalation reproductive toxicity studies showed no clear effects on reproductive performance or fertility. Maternally toxic concentrations caused decreased pup growth. The drinking-water reproductive NOAEL was 100?ppm (moderate confidence due to study limitations). The inhalation exposure reproductive and neonatal toxicity high confidence NOAEL was 45?ppm (first generation 90?ppm) (6?h/day). The inhalation reproductive toxicity study provides the most robust data for risk assessment. Based on the WoE evaluation, AN is not expected to be a developmental or reproductive toxicant in the absence of significant maternal toxicity.     

Inhalation Studies in Rats Exposed to Dimethylacetahide (DMAc) from 3 to 12 Hours Per Day

ABSTRACT

Male rats were exposed by inhalation from 10 to 300 ppm Dimethylacetamide (DMAc) for either 3, 6, or 12 hrs/day for a total of 10 exposures (5 exposures, 2 rest days, 5 exposures). Rats were observed daily for signs of DMAc-related effects, growth was monitored by body weights, clinical laboratory tests and microscopic examination of the liver, testes epididymides, and nasal passages were conducted. One half of the rats in each group was allowed a 14-day post-exposure period to evaluate the reversibility of DMAc-induced changes. No clinical signs of toxicity or DMAc-related gross changes at necropsy were seen in any of the rats although 1 rat exposed to 300 ppm for 12 hours per day died following the seventh exposure. Slight (< 5%) decreases in body weight gain were seen in rats exposed to 300 ppm for 6 or 12 hrs/day. Serum cholesterol levels were elevated in rats exposed to either 100 or 300 ppm (all exposure durations) and in rats exposed to 30 ppm for 12 hours. Total serum protein concentrations were increased in rats exposed for 12 hours/day to either 30, 100, or 300 ppm. Hepatocellular hypertrophy together with margination of hepatocellular cytoplasmic contents and lipid-like cytoplasmic vacuolation in hepatocytes were seen microscopically only in rats exposed for 12 hours/day to 300 ppm. Recovery from these liver changes was not complete after 14-day post-exposure period. No evidence of either testicular damage or irritation to the upper respiratory tract was seen.     

Effect of HPS on leucocytozoon and coccidial infection in chickens

The effect of HPS (halofuginonepolystyrene sulfonate), a derivative of halofuginone with lower toxicity, on natural leucocytozoon and coccidial infection in broiler chickens was evaluated in a floor pen trial. The experiment was conducted from one day to 10 weeks of age. On leucocytozoon infection, HPS added to the diet was completely effective at 60 ppm, fairly effective at 40 ppm and ineffective at 20 ppm. On the other hand, HPS concentrations of 20 ppm, 40 ppm and 60 ppm were completely effective on coccidial infection. HPS at 40 ppm which corresponds to the recommended level of halofuginone (3 ppm) and at 60 ppm had no adverse effect on the weight gain in experimental birds.     

Selenium toxicity: cause and effects in aquatic birds

There are several manners in which selenium may express its toxicity: (1) an important mechanism appears to involve the formation of CH(3)Se(minus sign) which either enters a redox cycle and generates superoxide and oxidative stress, or forms free radicals that bind to and inhibit important enzymes and proteins. (2) Excess selenium as selenocysteine results in inhibition of selenium methylation metabolism. As a consequence, concentrations of hydrogen selenide, an intermediate metabolite, accumulate in animals and are hepatotoxic, possibly causing other selenium-related adverse effects. (3) It is also possible that the presence of excess selenium analogs of sulfur-containing enzymes and structural proteins play a role in avian teratogenesis. L-selenomethionine is the most likely major dietary form of selenium encountered by aquatic birds, with lesser amounts of L-selenocysteine ingested from aquatic animal foods. The literature is suggestive that L-selenomethionine is not any more toxic to adult birds than other animals. L-Selenomethionine accumulates in tissue protein of adult birds and in the protein of egg white as would be expected to occur in animals. There is no suggestion from the literature that the levels of L-selenomethionine that would be expected to accumulate in eggs in the absence of environmental concentration of selenium pose harm to the developing embryo. For several species of aquatic birds, levels of Se as selenomethionine in the egg above 3 ppm on a wet weight basis result in reduced hatchability and deformed embryos. The toxicity of L-selenomethionine injected directly into eggs is greater than that found from the entry of L-selenomethionine into the egg from the normal adult diet. This suggests that there is unusual if not abnormal metabolism of L-selenomethionine in the embryo not seen when L-selenomethionine is present in egg white protein where it likely serves as a source of selenium for glutathione peroxidase synthesis in the developing aquatic chick.     

盐酸苯环壬酯对小鼠的围产期毒性试验研究

盐酸苯环壬酯分成２．５、１２．５和６２．５ｐｐｍ３个浓度组，溶于自一不中，供孕鼠从妊娠ｄ１５开始至断乳时饮用。结果显示，在相当于人临床用量１５－７５倍剂量范围内，该药对小鼠胚胎后期生长发育、母鼠分娩、哺乳及新生小鼠神经行为发育无明显影响。６２．５ｐｐｍ组孕鼠给药期间体重增长抑制，死产仔鼠数增多，雄仔鼠肝脏重量增加，表现出一定的母体毒性和发育毒性。     

Acute and Environmental Toxicity Studies with Hexazinone

Acute and Environmental Studies with Hexazinone. KENNEDY, G.L, JR. (1984). Fundam. Appl. Toxicol. 4, 603–611. Theacute toxicity of hexazinone, a herbicide intended for generalnoncropland areas and selected crop uses (alfalfa and sugarcane),has been evaluated to establish proper handling guidelines andto measure its potential impact on the environment The materialis slightly to moderately toxic when given as a single oraldose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs860 mg/kg, and in male dogs greater than 3400 mg/kg althoughin the dog emesis prevented accurate quantitation. When thematerial is administered intraperitoneally, the LD50 in ratsis 530 mg/kg. Repeated doses (five oral doses per week for 2weeks) of 300 mg/kg to rats produced slight weight loss in oneof two replicate experiments. In both studies, no gross or histologjcalterations were apparent Hexazinone is a moderate to severeeye irritant in the rabbit and produced only mild erythema inrabbit skin at 5278 mg/kg, a dose which did not produce lethalityor other clinical signs. Subchronic dermal exposures (10 consecutivedoses) to rabbits produced increases in serum alkaline phosphataseand glutamic-pyruvic transaminase at the highest levels tested(680 and 770 mg/kg in two separate experiments) with no effectsseen at 150 mg/kg. There were no alterations in livers fromtreated rabbits examined by light microscopy. No dermal sensitizationwas produced when concentrations of up to 50% were tested inguinea pigs. One-hour inhalation exposure of up to 7.48 mg/literdid not produce mortality in rats. In freshwater biota, thematerial had slight to low toxicity with 96-hr LC50 values beingbetween 370 and 420 mg/liter in bluegill sunfish, between 320and 420 mg/liter in rainbow trout, and 274 mg/liter in fatheadminnows. The 48-hr LC50 in Daphnia magna was 152 ppm. In marinebiota, similar low toxicity was indicated by a 48-hr EC50 of320 to 540 ppm in eastern oysters, a 96-hr LC50 of 56 to 100ppm in grass shrimp, and a 96-hr LC50 greater than 1000 ppmin fiddler crabs. Bobwhite quail were not killed by feedingof up to 10,000 ppm. When given to quail as a single oral doseby intubation, the LD50 value was 2258 mg/kg. Ducks survivedfeeding of 10,000 ppm indicating that the material has a loworder of toxicity in water fowl and upland game birds. Hexazinonehad a low order of acute toxicity when tested in mammals, freshwaterand marine biota, and birds. The material is an eye irritantand should be handled carefully. Dermal irritancy, sensitizationpotential, and systemic toxicity are low.