Toxicology of selected pesticides, drugs, and chemicals. Anticoagulant, cholecalciferol, and bromethalin-based rodenticides

The control of rodent pests is a continuing goal of mankind. To this end, a multitude of rodenticides have been produced, each designed to kill rodents by exerting their toxic effects on various body systems. As examples, veterinarians have had to manage companion animal poisonings due to anticoagulant, sodium fluoroacetate (compound 1080), thallium, barium carbonate, and zinc phosphide-based rodenticides. Many of these rodenticides were introduced because of their anticipated safety in relation to nontarget species; unfortunately, this has not been the case. Veterinarians must attempt to identify the specific rodenticide involved in poisoning cases. Therapeutic success in these poisonings is often more dependent upon symptomatic and supportive care rather than the use of antidotal therapy.     

Assessment of ruminal degradation, oral bioavailability, and toxic effects of anticoagulant rodenticides in sheep

OBJECTIVE: To assess the rate and extent of ruminal degradation of warfarin, chlorophacinone, and bromadiolone in vitro and determine the oral availability and clinical and hemostatic effects of each anticoagulant rodenticide in adult sheep. ANIMALS: 3 Texel sheep. PROCEDURE: Samples of ruminal fluid were incubated with each of the anticoagulants to assess the kinetics of ruminal degradation over 24 hours. To determine the plasma kinetics of the anticoagulants, each sheep received each of the anticoagulants IV or via a rumenimplanted cannula at 2-month intervals (3 rodenticide exposures/sheep). At intervals during a 240- to 360- hour period after treatment, prothrombin time (PT) was measured, plasma anticoagulant concentration was assessed, and clinical signs of rodenticide poisoning were monitored. In plasma and rumen extracts, anticoagulant concentrations were determined via high-performance liquid chromatography. RESULTS: In the rumen extracts, anticoagulants were slightly degraded (< 15%) over 24 hours. In vivo, oral availability of warfarin, chlorophacinone, and bromadiolone was estimated at 79%, 92%, and 88%, respectively. Although maximum PT was 80 seconds after chlorophacinone and bromadiolone treatments, no clinical signs of toxicosis were detected; PT returned to baseline values within 2 weeks. CONCLUSIONS AND CLINICAL RELEVANCE: In sheep, warfarin, chlorophacinone, and bromadiolone were not degraded in the rumen but their bioavailabilities were high after oral administration; the kinetics of these compounds in sheep and other mammals are quite similar. These data suggest that the lack of susceptibility of ruminants to these anticoagulant rodenticides cannot be explained by either ruminal degradation or the specific toxicokinetics of these anticoagulants.     

Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration

The first aim of the study was to investigate the pharmacokinetics of eight anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone, coumatetralyl, difenacoum, difethialone, flocoumafen and warfarin) in plasma and liver of the mouse after single oral administration. Eight groups of mice dosed orally with a different anticoagulant rodenticide in a dose equal to one‐half the lethal dose 50 (LD₅₀), were killed at various times up to 21 days after administration. The eight anticoagulant rodenticides were assayed in plasma and liver by an LC‐ESI‐MS/MS method. Depending on the compound, the limit of quantification was set at 1 or 5 ng/mL in plasma. In liver, the limit of quantification was set at 250 ng/g for coumatetralyl and warfarin and at 100 ng/g for the other compounds. The elimination half‐lives in plasma for first‐generation rodenticides were shorter than those for second‐generation rodenticides. Coumatetralyl, a first‐generation product, had a plasma elimination half‐life of 0.52 days. Brodifacoum, a second‐generation product, showed a plasma elimination half‐life of 91.7 days. The elimination half‐lives in liver varied from 15.8 days for coumatetralyl to 307.4 days for brodifacoum. The second aim of the study was to illustrate the applicability of the developed method in a clinical case of a dog suspected of rodenticide poisoning.     

Crimidine (2‐chloro‐4‐(dimethylamino)‐6‐methylpyrimidine) poisoning in a dog due to ingestion of the rodenticide Castrix®

The diagnosis and treatment of a case of crimidine poisoning in a dog are described. Presenting signs were seizures and vomiting. The vomitus contained a purple coloured cereal grain. The signs and grain colour were suggestive for a rodenticide with convulsive effects The diagnosis of crimidine poisoning was made by thin layer chromatography and was later confirmed by finding the source of the poison. Except for the administration of Vit B6, the specific antidote for crimidine, general treatment principles for poisoning were followed. The treatment of crimidine poisoning is time consuming and requires intensive care facilities.     

Rodenticides.

Rodenticides are second only to insecticides in the prevalence of pesticide exposure. Hundreds of rodenticide products currently exist, yet only a handful of them are involved in most toxicoses of companion animals. The most commonly reported toxicoses in the United States are those caused by anticoagulant rodenticides, bromethalin, cholecalciferol, strychnine, and zinc phosphide. The pathophysiologic findings, diagnosis, and treatment of each of these five rodenticides are discussed.     

高山兀鹫（Gyps himalayensis）的繁殖行为研究

大型猛禽行为研究难度大,方法落后,国内尚处在摸索阶段.高山兀鹫（Gyps himalayensis）是中亚及青藏高原特有物种,对其繁殖行为研究几乎空白.2012 ～ 2014年,在新疆天山中段采用路线调查法和行为扫描法,结合访问,探寻高山兀鹫的繁殖巢区及观察育雏过程.同时通过实地观测、迷你自动相机拍摄等方法,开展了栖息地调查、巢数统计、巢结构分析、孵化过程及雏鸟生长发育观察、繁殖周期及食物组成分析等.对天山7个地点的14个巢区及上百个巢穴统计,结果发现高山兀鹫喜欢在朝南的崖壁上集群营巢（约占78.6％）,窝卵数为1枚（n=21）,最长的一个繁殖区（A区）绵延7.3 km,相距另外一个较近的巢区（B区）约47 km.其巢的结构特殊,均以细禾草铺垫.随着幼鸟长大,亲鸟的护幼强度逐渐减弱.为了错开产卵时间,其种群的整个繁殖周期长达8 ～10个月（1～10月）,超出其他大型猛禽平均繁殖周期1倍的时间.因为食物缺乏,其育雏期可能被迫延迟.对高山兀鹫的主要威胁来自人类的过度放牧、采矿、药物滥用、捡蛋与捉幼鸟等.加强猛禽保护,迫在眉睫.还讨论了兀鹫与狼、雪豹及天葬的关系.     

金蟾速补钙（畜禽钙锌预混料）对蛋雏鸡育雏期饲喂效果试验

在蛋雏鸡育雏期添加金蟾速补钙（畜禽钙锌预混料）进行饲喂,观察育雏期每周鸡群采食量和雏鸡死亡数,并按2%比例抽样称重,计算鸡群均匀度。结果试验组雏鸡质量和鸡群均匀度明显优于对照组,差异显著（P〈0.05）;试验组采食量和雏鸡总死亡数高于对照组,但差异不明显。试验结果提示,在蛋鸡育雏期使用金蟾速补钙（畜禽钙锌预混料）可以提高育雏生产性能,可在生产上推广应用。     

用杀鼠剂和饵料对达乌尔黄鼠进行防治正交试验研究

为筛选出防治达乌尔黄鼠的杀鼠剂及其施用技术,用3种杀鼠剂、3个用药浓度、3个投饵量和3种饵料进行L9(34)正交试验,经方差分析和F检验发现,各因子对灭洞率的有效性自大至小顺序为:杀鼠剂用药浓度投饵量饵料种类。以灭洞率为评价指标,对不同因子各水平进行SSR测验证明:3种参试杀鼠剂的有效性依次为溴鼠灵(87.56%)C型肉毒梭菌生物毒素(80.00%)敌鼠钠盐(73.89%);灭洞率随用药浓度和投饵量变化,用药浓度越大、投饵量越多,灭洞率亦越高;用玉米、苜蓿草颗粒和玉米秸秆草颗粒作饵料灭洞率差异不显著,表明用苜蓿草颗粒和玉米秸秆草颗粒代替粮食作达乌尔黄鼠的饵料是可行;A2B3C2D3(0.15%的溴鼠灵、苜蓿草颗粒作饵料、每个有效洞口投25粒毒饵)是最佳处理组合。     

Effect of oxygen supplementation in the hatcher at high altitude on the incubation results of broiler eggs laid at low altitude

1. The object of this research was to investigate the effects of high altitude with supplementary oxygen during the last stage of incubation of broiler eggs laid at low altitude and incubated at low and high altitude. We analysed thyroid hormones and haematological variables. 2. The treatment groups were: low altitude (LA), high altitude with oxygen supplementation in the hatcher (HA-OX) and high altitude non-oxygen-supplemented (HA-NOX). 3. High altitude affected relative egg weight loss and early embryonic mortality. The hatchability of fertile eggs was lower at high than at low altitude. 4. Oxygen supplementation into the hatcher cabinet during the last stage of incubation decreased late embryonic mortality ratio (LEM(1)) and improved survival rates of embryos incubated at high altitude. 5. Eggs incubated at low altitude had a higher hatched chick weight and relative chick weight than those incubated at high altitude. Hatched chick weight and relative chick weight did not change with oxygen supplementation at high altitude. 6. High altitude caused an increase in plasma T(3) and T(4) concentrations as well as in the ratio of T(3):T(4) in embryos. High altitude newly hatched chicks showed a higher T(3):T(4) ratio than low altitude chicks; this ratio decreased with oxygen supplementation at high altitude. Altitude and oxygen supplementation did not affect the mean plasma T(4). 7. Newly-hatched chicks incubated at high altitude showed a higher plasma haematocrit (PCV) than the newly-hatched chicks from eggs incubated at low altitude. High altitude without supplementation increased haemoglobin (Hb), while oxygen supplementation returned the value to low altitude values.     

Diagnosis and therapy of anticoagulant rodenticide intoxications

The mechanism of toxicity and agents of anticoagulant rodenticides are discussed. The diagnosis of anticoagulant poisoning is outlined and discussed by applying clinical, laboratory, and therapeutic response measures as a means to confirm poisoning. Additional therapeutic concerns and newly developed diagnostic tests are discussed. Application of the therapeutic and diagnostic measures provides a successful plan to manage anticoagulant poisonings.     

高原鼠兔的精确性可持续控制技术研究——几种杀鼠剂的对比试验

于2007年4-5月份在甘肃肃南县对防治高原鼠兔精确用药进行试验,将5种常见杀鼠剂的推荐用药浓度、用药量按等比级数增、减剂量进行插组,作正交对比试验,结果表明,推荐用药浓度、用药量和饵料种类与调整后的用药浓度、用药量和饵料种类对高原鼠兔的灭洞率有一定的差异性。影响灭洞率的主、次因子顺序是:杀鼠剂＞用药浓度＞投饵量＞饵料种类。以防效为评价指标,5种参试杀鼠剂的排序为:大隆(83.9%)＞D型肉毒梭菌生物毒素(82.6%)＞溴敌隆(79.4%)＞C型肉毒梭菌生物毒素(75.0%)＞敌鼠钠盐(68.9%)。最佳处理组合是: 1)用0.15%的D型肉毒梭菌生物毒素、小麦饵料、25粒投饵量;2) 0.01%大隆、青稞饵料、5 g投饵量;3) 0.01%溴敌隆、小麦饵料、3 g投饵量。     

几种灭鼠剂对高原鼠兔的灭鼠效果对比试验

应用4种灭鼠剂进行杀灭高原鼠兔的对比试验,从灭效和对环境的影响以及对人畜的安全性等方面的调查,认为采用生物灭鼠剂进行草原灭鼠效果更理想。     

GROWTH RATE OF OSTRICH (STRUTHIO CAMELUS) CHICKS UNDER INTENSIVE MANAGEMENT IN BOTSWANA

Thirty-seven ostrich chicks raised artificially had their weights, lengths of metatarsus and heights measured weekly from hatching to the 16th week. Despite weight loss during the first week due to utilization of egg yolk by the chicks, the chicks showed an exponential growth up to the twelfth week with an overall mean weekly weight gain of 1.3 kg. Female chicks showed a superior mean weekly gain of 1.6 kg compared to 1.2 kg for males. The metatarsal length grew rapidly at a weekly rate of 2.5 cm, but began to decline in the 11th week even though the weights and heights of the chicks were still increasing. The correlation coefficient between body weight and metatarsal length was 0.97. Individual chicks also maintained their respective heavy or light weight hierarchies throughout the study period. Thus isolation of chicks into groups by weight and raising them separately could have a role in the artificial rearing of ostrich chicks. Furthermore, ostrich chick rearing may be improved by regularly weighing chicks as a means of detecting changes in the growth patterns.     

Relationship between the weight of hatching eggs and subsequent early performance of broiler chicks

1. The effect of egg weight on the subsequent performance of individual growing chicks was studied. Eggs from commercial broiler breeder hens were collected at 52, 55 and 57 weeks of age and incubated. The chicks were reared for 18 d. 2. Egg weight and hatched chick weight were not affected by the age of the hens during the 52 to 57-week period, but there was a close correlation between egg weight and hatching weight, irrespective of the age of the hens (r = 0.89). Chick:egg weight ratio at hatching was about 0.71 and independent of hen age. One d after hatching, chick weights had decreased by about 1.5 g. 3. The initial high correlation between egg weight and chick weight decreased markedly during post-hatching growth, becoming insignificant 5 d after hatching. At 18 d of age, however, chicks from eggs of older hens tended to be heavier than those from younger birds. The greater 18-d weights appeared to be associated more with higher food intake during that period, than with greater egg weight. 4. It was concluded that, in individual broiler chicks, the advantage of the initially higher weight attributable to a larger egg diminishes rapidly after hatching, and the main factor affecting final body weight is food intake.     

Toxicity of a vitamin D3 rodenticide to dogs

As a follow-up to an investigation of 2 dogs that died as a result of apparent toxicosis attributable to a cholecalciferol-containing rodenticide, we tested the toxicity of this product in dogs. Two groups of 2 dogs each were fed amounts of rodenticide that provided 20 and 10 mg of cholecalciferol/kg of body weight (approx one fourth and one eighth of the published LD50, respectively). All dogs developed hypercalcemia and hyperphosphatemia and then died. Major lesions were gastrointestinal hemorrhage, myocardial necrosis, and mineralization of vascular walls. Our data indicate that cholecalciferol-containing rodenticides pose a much greater hazard to dogs than was previously believed.     

Raptor toxicology.

Birds of prey have demonstrated the negative impact that toxic agents can cause on animal populations and ecosystem dynamics. Lead, cholinesterase inhibitors (eg, organophosphates, carbamates), and anticoagulant rodenticides (eg, brodifacoum) are the most common toxic agents that currently affect the health of wild birds of prey in the United States. For raptors held in captivity, the list of toxic agents expands and includes toxic inhalants such as carbon monoxide and polytetrafluoroethylene. This article provides diagnostic and treatment guidelines for the toxic agents discussed.     

Factors related to high levels of ostrich chick mortality from hatching to 90 days of age in an intensive rearing system

Ostrich chick mortality was studied in 2522 chicks that were hatched artificially during the 1999/2000 breeding season. High levels of mortality were observed, with 1978 (78.4 %) of these chicks dying before 90 days after hatching. A total of 46.7 % (1,177) of these chicks died before 28 days of age, and a further 30.7% (801) died between 28 and 90 days post-hatching. Chick mortality to 28 days of age could not be conclusively related to sex, day of external pipping or breeder diet. Mortality rates were higher (P< 0.05) at the beginning and end of the breeding season than in the middle months. Differences in mortality levels of chicks incubated in different incubators could be related to the time of the breeding season during which the incubator was mostly used. The regression of chick mortality to 28 days of age on day-old chick mass followed a 2nd-degree polynomial. Chicks with day-old masses below 762.5 g were particularly at risk of dying before 28 days after hatching. Chicks hatching from eggs where excessive water loss to 35 days of incubation (>18%) was recorded were also at risk of succumbing before 28 days of age. Chick mortality percentages for the period from 28 to 90 days of age exceeded 80 % in chicks weighing an average of 1.050 g at 28 days. Mortality percentages declined sharply at higher live masses, to between 20 and 30 % in chicks weighing > or = 1,950 g. This 'core' level of mortality remained throughout, even in the heaviest chicks. It was concluded that the high levels of chick mortality could be related to stress in chicks, resulting from an inability to adapt to the rearing environment. The high subsequent mortality percentages of low live mass chicks that survived to 28 days after hatching could probably be attributed to residual setbacks suffered earlier. Abetter understanding of the underlying principles involved in ostrich chick mortality in intensive rearing environments is required for progress in this field, resulting in more predictable survival rates under these conditions.     

Ontogeny of hepatic methionine catabolic enzyme activities (Transmethylation and Transsulphuration) and associated physiological amino acids in E10-21 chick embryos and D1-49 broilers

Developmental changes in hepatic methionine adenosyltransferase, cystathionine β-synthase, cystathionase, and glycine N-methyltransferase were determined in broiler chick embryos and hatched chicks by using radiometric and spectrometric methods. Hepatic free methionine, S-adenosylmethionine, S-adenosylhomocysteine, homocysteine, cystathionine, and cysteine levels were also investigated. Results showed an increase in hepatic MAT activity from E10 to E21 during embryogenesis, suggesting greater transmethylation rates throughout the rapid embryonic growth and development period. A strong positive correlation between embryo BW and MAT activity also supports this idea. The MAT specific activity continued to increase after hatching, but there was a negative correlation between chick BW and MAT activities from D1 to D49. This may indicate different MAT isozymes exist for chick embryo hepatic tissue compared to hepatic tissue of hatched chick and growing broilers. The developmental pattern of MAT isozymes could be critical for methionine metabolism to cope with the demand imposed on the embryo, chicks, and growing broilers. Additionally, the specific activity of hepatic CBS in chick embryos was determined to be lower compared to that observed in older broilers (35 and 49 days). Since liver CBS specific activity is at the lowest point from D1-7 in young chicks, the ability to convert adequate homocysteine to cysteine through transsulphuration may be limiting for cysteine synthesis at this time. Steady-state hepatic homocysteine levels in chick embryos and chicks may be a function of the rates of homocysteine formation, remethylation, and catabolism via the transsulphuration pathway. The present study indicates young chicks from D1 to D7 may have a limited ability for adequate transsulphuration; therefore, dietary cystine may be needed for optimum performance.     

The release of a troop of rehabilitated vervet monkeys (Chlorocebus aethiops) in KwaZulu-Natal, South Africa: outcomes and assessment

Rehabilitation and release have become central to the management and welfare of primate species in South Africa such as the vervet monkey (Chlorocebus aethiops). However, limited research means that it is unknown whether rehabilitation is a successful management strategy for this species. This study describes the release of a troop of rehabilitated vervet monkeys and evaluates the results of 1 year of post-release monitoring. The released animals exhibited wild behaviours and established a home range. Survival could not be adequately evaluated due to the high number of untraceable animals, and troop composition was significantly different from that of wild troops. Improvement may be gained by radio-collaring more animals using improved technology, ensuring that troop composition is comparable to wild troops, excluding ex-pets from re-introduction and a more detailed assessment of the release site.     

Nutrition and metabolism in poultry: role of lipids in early diet

Modern strains of broiler chickens are selected for fast growth and are marketed anywhere from 36 to 49 days after a21-day incubational period. For a viable healthy chick, all the necessary nutrients required for growth and development must be provided by the hen through the fertilized egg. The current feeding strategies for improved growth, health and productivity are targeted towards chicks after hatching. Considering the fact that developing chick embryo spends over 30 % of its total life span inside the hatching egg relying on nutrients deposited by the breeder hen, investigations on nutritional needs during pre-hatch period will improve embryonic health, hatchability and chick viability. In this context, investigations on hatching egg lipid quality is of utmost importance because, during incubation, egg fat is the major source of energy and sole source of essential omega-6(n-6) and omega-3(n-3) fatty acids to the chick embryo.Due to the unique roles of n-3 and n-6 fatty acids in growth, immune health, and development of central nervous system, this review will focus on the role of early exposure to essential fatty acids through maternal diet and hatching egg and its impact on progeny in meat-type broiler chickens.