Effects of 4-dimethylaminophenol and Co2EDTA on circulation,respiration, and blood homeostasis in dogs

The effects of intravenously injected 4-dimethylaminophenol and Co₂EDTA on peripheral circulation, respiration, acid-base balance, and several other physiological and biochemical parameters were studied on dogs. DMAP increased the respiratory minute volume and mean arterial pressure, diminished the lactate-to-pyruvate ratio, and induced an increase in arterial oxygen pressure caused by liberation of oxygen from oxyhemoglobin during the formation of ferrihemoglobin.A study in vitro of the fate of the oxygen during the reaction between DMAP and oxyhemoglobin showed that only 30–40% of the oxygen released by the formation of ferrihemoglobin appeared in the gas phase.Co₂EDTA caused circulatory depression, hyperventilation, and metabolic acidosis resulting in a decrease in base-excess and pH. The concentrations of lactate, pyruvate, potassium, and urea nitrogen and the hemoglobin content were increased by Co₂EDTA. The side effects of Co₂EDTA in therapeutic doses were more serious than those of DMAP. Thus the latter is superior in the therapy of cyanide poisoning, all the more since it detoxifies more cyanide.     

Effects of 4-dimethylaminophenol and Co2EDTA on circulation, respiration, and blood homeostasis in dogs.

The effects of intravenously injected 4-dimethylaminophenol and Co2EDTA on peripheral circulation, respiration, acid-base balance, and several other physiological and biochemical parameters were studied on dogs. DMAP increased the respiratory minute volume and mean arterial pressure, diminished the lactate-to-pyruvate ratio, and induced an increase in arterial oxygen pressure caused by liberation of oxygen from oxyhemoglobin during the formation of ferrihemoglobin. A study in vitro of the fate of the oxygen during the reaction between DMAP and oxyhemoglobin showed that only 30--40% of the oxygen released by the formation of ferrihemoglobin appeared in the gas phase. Co2EDTA caused circulatory depression, hyperventilation, and metabolic acidosis resulting in a decrease in base-excess and pH. The concentrations of lactate, pyruvate, potassium, and urea nitrogen and the hemoglobin content were increased by Co2EDTA. The side effects of Co2EDTA in therapeutic doses were more serious than those of DMAP. Thus the latter is superior in the therapy of cyanide poisoning, all the more since it detoxifies more cyanide.     

Effects of 4-dimethylaminophenol,Co2EDTA,or NaNO2 on cerebral blood flow and sinus blood homeostasis of dogs in connection with acute cyanide poisoning

The effects of the cyanide antidotes DMAP, Co₂EDTA, and NaNO₂ on cerebral blood flow (CBF) and cerebral blood gases were investigated in connection with acute poisoning of dogs by cyanide. The substances were injected intravenously. Local CBF as measured with thermocouples in the cingulum increased by 100–200% after a non-lethal dose of KCN (1 mg/kg) and by 50% after injection of NaNO₂ (15 mg/kg), that oxidized some 20% of the total hemoglobin to ferrihemoglobin. Co₂EDTA (10 mg/kg) induced a decrease in local CBF of 30% and in brain temperature of 0.5°C. The temperature diminished also after poisoning by KCN, but it rose by 0.15°C after the administration of NaNO₂. Local CBF and sinus sagittalis blood flow increased by 60–160% for about 15 min, and the brain temperature decreased by 0.4–0.5°C when DMAP (3.25 mg/kg) or Co₂EDTA (15 mg/kg) was injected 1 min after poisoning by cyanide (4 mg/kg), a dose that always caused respiratory arrest. Immediately after injection of DMAP the brain temperature rose transiently by 0.1–0.2°C. Co₂EDTA did not exert such an effect. In the sinus sagittalis blood of artificially ventilated animals pCO₂ decreased rapidly by 10–20 mmHg after poisoning and approached the initial level after treatment with DMAP or Co₂EDTA. The highest value of pO₂ was about 80 mmHg and 50 mmHg after injection of DMAP and Co₂EDTA, respectively; thereafter pO₂ declined to 20 mmHg or 40 mmHg at 20 min. The lactate concentration increased by 60–70% without tendency to return to normal.     

The effect of prior treatment with 4-dimethylaminophenol (DMAP) on animals experimentally poisoned with hydrogen cyanide

Six dogs were given sufficient oral 4-dimethylaminophenol (DMAP) to produce a peak methaemoglobin level of 12–15%. Five out of the six dogs then survived an intravenous injection of approximately 2 LD₅₀'s of hydrogen cyanide given when the methaemoglobin had reached 8–10%. The sixth dog died after 44 min. When the same dose of hydrogen cyanide was given to dogs, not previously given DMAP, all three died within 11/2 min. It was concluded that prior treatment with oral DMAP provided a large measure of protection against cyanide poisoning. Comparison of cyanide levels in whole blood and plasma in the two groups of dogs lent support to the hypothesis that methaemoglobin complexed with cyanide in the erythrocytes causing the plasma cyanide to remain lower than it did in unprotected animals.     

Zur Beurteilung der Blausäure-Antidote

The effect of various antidotes on the exhalation of hydrocyanic acid has been measured in guinea pigs and cats poisoned with cyanide. This procedure permits evaluation of both the speed of action and the capacity of the agents tested to detoxify hydrocyanic acid, and therefore allows an exact judgement as to therapeutic value of various antidotes to cyanide poisoning. The results were as follows:

1. Cobaltous histidine at a dose of 20 mg/kg was distinguished among the compounds tested by its rapid action in both species. Its detoxifying capacity was not adequate however. Treatment of severe cyanide poisoning in man with Co (his)₂ would appear to be reasonable, but only when combined with sodium thiosulfate.
2. The same rapid action as with cobaltous histidine was achieved in cats by intravenous injection of 2.25 mg/kg p-dimethylaminophenole (DMAP) leading to a methemoglobin formation of 30%. A dose of 0.75 mg/kg DMAP forming 10% methemoglobin reduced HCN-exhalation by an equivalent amount only after a 2.4 min delay. The capacity of DMAP to detoxify hydrocyanic acid was considerably greater than that of cobaltous histidine but still was far inferior to that of sodium thiosulfate.
3. The high capacity of sodium thiosulfate to detoxify hydrocyanic acid was likewise demonstrated by the new method employed here in both animal species. However, the onset of its effect was always very delayed. In clinical practice, this agent should never be omitted, but in treatment of severe poisonings it will only be successful when combined with a more rapid-acting antidote such as cobaltous histidine or DMAP.
4. Sodium nitrite, even when applied in relatively high doses, did not act rapidly enough nor did it demonstrate a satisfactory capacity to detoxify hydrocyanic acid. Therefore, it no longer fulfills the requirements that presently should be demanded of an antidote to hydrocyanic acid.

     

对二甲氨基酚治疗急性失血合并氰中毒对血液动力学及血液内环境的影响

本实验用犬制备了轻(10％)、中(15％)、重度(20％)急性失血合并ⅳ NaCN 2.5 mg/kg中毒的动物模型,观察了ⅳ DMAP 2.5mg/kg治疗时血液动力学及血液内环境的变化。结果发现,DMAP治疗轻度急性失血合并氰中毒能使心血管功能迅速恢复正常并维持稳定,随失血程度加重DMAP对心血管功能兴奋作用减弱;血气分析及HbFe~(3+)测定结果表明,DMAP治疗急性失血合并氰中毒可造成机体严重缺氧及代谢性酸中毒,并随失血程度的加重而加剧。     

对二甲氨基酚,依地酸二钴和亚硝酸钠对犬心脏血流动力学的影响

本文观察了DMAP,Co_2 EDTA和NaNO_2对犬心脏血流动力学的影响。iv DMAP 3.2mg/kg后LVP及其±dP/dtmax短暂轻度增加,CI,MAP,TPVR,LVWI和HR在30 min内基本稳定,至60 min时CI,LVWI和-dp/dtmax下降。iv Co_2EDTA 15mg/kg或NaNO_2 20 mg/kg后10 min MAP,CI,LVWI,LVP,±dP/dtmax及TPVR(Co_2EDTA组除外)降低最明显,60 min时NaNO_2组CI,MAP,TPVR,LVP和LVWI及Co+2EDTA组CI和LVWI仍然下降。Co_2EDTA组TPVR 1min时下降,5 min见恢复,60min上升。表明(1)DMAP能维持血压和外周血管张力平稳,使心脏舒缩性能短暂轻度增强;(2)Co_2EDTA初期降压系由其扩张血管和抑制心功能所致,后期降压主要由后者引起;(3)NaNO_2降压作用系通过扩张外周血管和抑制心功能所致。     

Pharmacokinetics of cyanide in poisoning of dogs,and the effect of 4-dimethylaminophenol or thiosulfate

Cyanide in blood, plasma, and urine of dogs after administration of K¹⁴CN was determined with the isotope dilution technique. The addition of large amounts of inactive KCN as soon as possible to a sample to be analyzed inhibited the decrease of the original cyanide concentration.After administration of several lethal doses of cyanide into the stomach or by slow intravenous infusion a concentration of about 40 M cyanide in plasma was found at the moment of respiratory arrest. Since 60% of the cyanide in plasma was bound to proteins the concentration of free cyanide which stopped respiration was about 16 M.Quick formation of ferrihemoglobin by i.v. injection of 4-dimethylaminophenol after plasma cyanide had risen to or above 40 M decreased the cyanide concentration in plasma and restored respiration, while cyanide was accumulated in red cells by formation of ferrihemoglobin cyanide.Equilibrium constants calculated for the reaction between ferrihemoglobin and cyanide in vivo indicated that the reaction approached equilibrium in a few minutes.Up to 60% of the radioactive cyanide absorbed was found as non-cyanide radioactivity in the urine.Abbreviations Used DMAP 4-Dimethylaminophenol hydrochloride - HbFe²⁺ Ferrohemoglobin - HbFe³⁺ Ferrihemoglobin - HbFe³⁺CN^– Ferrihemoglobin cyanide - C_a Molarity of all radioactive compounds calculated on the assumption that one mole cyanide yields one mole metabolite - NCR Molarity of non-cyanide radioactive compounds calculated on the assumption that one mole cyanide yields one mole of metabolite (C_a-[CN^–])     

Effects and biotransformation of 4-dimethylaminophenol in man and dog

The cyanide antidote 4-dimethylaminophenol . HCl (DMAP) was administered orally, i.v., or i.m. to man and dog. Ferrihemoglobin formation and changes of several parameters in human blood were investigated to obtain information on damage to liver, kidney, muscle, and red blood cells; in addition, the metabolism of DMAP was studied. In dogs, the initial rate of ferrihemoglobin production (DMAP, 3.25 mg/kg i.v. or i.m., 15 mg/kg orally) amounted to 28%, 3.5%, and 2% of the total hemoglobin per min; the corresponding values for man were 9%, 2%, and 2% per min. The dogs behaved normally while CPK increased after i.m. injection. In man, only i.m. injection of DMAP (3.25 mg/kg) was followed by increases in LDH, GOT, and CPK of 110, 260, and 490%, resp.; while total bilirubin, conjugated bilirubin, and iron concentration rose by 270, 120, and 50%, respectively. Bilirubin and iron concentration increased also after DMAP i.v. (3.25 mg/kg) or when it was taken orally (600 or 900 mg). The lactate concentration was not influenced while the pyruvate concentration increased by 50%. DMAP produced hemolysis in vitro. Generally, the values determined in vivo approached the starting level within 1 week. Intramuscular injection of DMAP induced reversible subjective and objective symptoms, e.g., local pain, swollen buttock, fever reaction. The urine showed no pathological changes. About 54% of DMAP taken orally was excreted as metabolites in the urine, 41% as glucuronide, 7% as sulfate, and 6% as thioethers. After i.v. administration the total of metabolites was somewhat higher, and the thioether proportion was 15%. The results indicate that DMAP is readily absorbed after oral administration but undergoes significant first pass effect in the liver. Therefore, the 4-fold i.v. dose must be administered orally to achieve the same ferrihemoglobin formation.     

Comparison of hydroxylamine, 4-dimethylaminophenol and nitrite protection against cyanide poisoning in mice

Intraperitoneal doses of 4-dimethylaminophenol hydrochloride (DMAP), hydroxylamine hydrochloride (H₂NOH) and sodium nitrite (NaNO₂) were found where each converted a maximum of about 37% of the total circulating hemoglobin in mice to methemoglobin. Those doses in mmol/kg were: 0.29 for DMAP, 1.1 for H₂NOH, and 1.1 for NaNO₂. For DMAP and H₂NOH the peak was sharp and at about 7 min after injection whereas for NaNO₂ the peak was much broader and at about 40 min. The i.p. LD₅₀'s in mmol/kg were: 0.48 for DMAP, 1.8 for H₂NOH and 2.3 for NaNO₂. When mice pretreated with each of the methemoglobin-generating agents were challenged with sodium cyanide, the ratios of the LD₅₀'s in protected mice to those in control mice (protection index, PI) were 1.5 for H₂NOH, 2.0 for DMAP and 3.1 for NaNO₂. When sodium thiosulfate was also given in combination with each of the three methemoglobin-generating agents, the protective effect was at least additive. The PI against sodium sulfide was also significantly greater in mice pretreated with NaNO₂ than in mice given H₂NOH. Methemoglobins generated from human and mouse hemoglobins by either NaNO₂ or by H₂NOH had identical binding affinities (dissociation constants) for cyanide. When human red cells containing methemoglobin generated by exposure to either NaNO₂ or H₂NOH were injected into the peritoneal cavity of mice and then followed by cyanide challenges, there was no difference in the PI for the two kinds of methemoglobin. Not only was the PI the same in each case with human cells, but it was also identical with that in mice given NaNO₂ systemically to generate the same total amount of methemoglobin. The difference in PI between NaNO₂ and H₂NOH (or DMAP) in mice appears to be related to the high rate of methemoglobin reductase activity in mouse RBC. It appears likely that cyanmethemoglobin is a substrate for mouse methemoglobin reductase activity, and that NaNO₂ is an inhibitor of mouse methemoglobin reductase. No differences in cyanide antagonism between NaNO₂ and H₂NOH would be anticipated in humans because of the slow rates of methemoglobin reduction in human red cells.     

Acute lead poisoning of the pigeon induced by single,intraperitoneal administration of lead acetate

A single dose of lead acetate (either 30 mg/kg or 150 mg/kg) was intraperitoneally (i.p.) adminstered to adult feral pigeons, Columba livia var and the effects of calcium disodium ethylenediamine tetraacetate (CaNa₂EDTA), (0, 150, 300, 600 mg/kg), administered i.p. twice a week in the ensuing period were observed. Lead acetate caused dose related mortality and decreases in weight, hematocrit and -aminolevulinic acid dehydratase activity (ALA-D). Acute toxicity of lead acetate in the pigeon, when given intraperitoneally, appeared approximately equivalent to that in the rat and mouse in terms of LD₅₀. Blood lead (blood Pb) levels observed during the lethal stage were five to ten times less than those reported for chronic oral lead poisoning in the pigeon. Biological implications of elevated levels of blood Pb observed in the feral pigeon in the urban Tokyo area are discussed. CaNa₂EDTA induced dose related recovery in ALA-D in 30 mg/kg group, and reduction of blood Pb levels in the group dosed with 150 mg/kg of lead acetate.     

术中iv维生素C对心脏手术患者术后肺部并发症的影响

目的 观察术中iv维生素C对心肺转流下行心脏手术患者术后肺部并发症的影响。方法 选取2018年12月—2019年8月在徐州医科大学附属医院择期在心肺转流下行心脏手术最终的70例患者为研究对象,采用随机序列法将患者分为对照组（37例）和维生素C组（33例）。维生素C组患者分别在麻醉诱导后10 min、体外循环后并行开始前10 min、胸骨完全闭合后予iv维生素C注射液,1 g用生理盐水稀释至10 mL,总量3 g。对照组患者在同等时间静脉注射10 mL生理盐水。记录患者术后肺部并发症发生率、严重度评分及种类。分别于插管后10 min（T₀）、胸骨完全闭合后（T₁）、术后第1天（T₃）、术后第3天（T₃）记录患者氧合指数（PaO₂/FiO₂）、肺泡动脉血氧分压差（A-aDO₂）。并于T₀、T₁记录肺动态顺应性（Cd）、肺静态顺应性（Cs）。观察患者术后其他并发症发生情况。结果 与T₀时刻比较,两组T₁~T₃时刻PaO₂/FiO₂、A-aDO₂明显降低（P<0.01）;两组T₁时刻Cd、Cs明显升高（P<0.05）。维生素C组术后肺部并发症发生率为12.12%,显著低于对照组的29.73%（P<0.05）。与对照组相比,维生素C组患者术后肺部评分显著降低（P<0.01）。术后患者其他并发症以房颤最常见,但两组间差异无统计学意义。结论 术中iv维生素C能够降低心脏手术患者术后肺部并发症评分,减少术后肺部并发症发生率,改善患者的肺功能。     

Cerebral blood flow,circulation, and blood homeostasis of dogs during slow cyanide poisoning and after treatment with 4-dimethylaminophenol

The effects of 4-dimethylaminophenol · HCl (DMAP) and 100% oxygen on cerebral blood flow (CBF) and peripheral circulation, arterial and venous blood gases, and other parameters have been investigated in dogs in the course of slow cyanide infusion.The i.v. infusion of KCN increased the respiratory minute volume, accompanied by a rise in arterial pO₂ and pH and a decrease in arterial pCO₂ while the venous lactate concentration increased by about 500% and the hemoglobin content and hematocrit by about 30%. Heart rate and carotid artery blood flow decreased. Local CBF in the cingulum as measured with thermocouples rose steadily, and the brain and oesophagus temperature were lowered. The breathing of 100% oxygen raised the local CBF, the temperature, and the arterial pCO₂.During the infusion of KCN into the femoral artery of artificially ventilated dogs the femoral venous pO₂ increased continuously by some 40 mm Hg, attended with a decrease in pCO₂ of 15 mm Hg. The femoral blood flow, however, rose sharply within 3 min. 100% oxygen induced a rise in pCO₂ and a diminution of pH in the femoral vein and in the sinus sagittalis, and the femoral flow rose rapidly.After DMAP i.v. the values of most of the parameters returned to normal or finally stabilized below or above the initial level. The rise in the hemoglobin content, hematocrit, and lactate concentration was stopped, but the arterial and venous pH remained or were lowered. DMAP elicited a rapid, strong decrease in the pO₂ of the femoral vein and the sinus sagittalis with a concomitant marked increase in pCO₂.     

The treatment of experimental cyanide poisoning by hemiglobin formation

Summary Following the observation that some aminophenols produce hemiglobin rather rapidly in vivo and in vitro and with regard to the need of rapid hemiglobin formation in the treatment of cyanide poisoning, o-aminophenol hydrochloride was tried in cyanide poisoning of mice and dogs.In mice o-aminophenol was found to produce hemiglobin more rapidly than an equally effective dose of nitrite.The injection of o-aminophenol hydrochloride saved 95% of the mice injected subcutaneously with two DL₅₀ of potassium cyanide. Only 60% of these mice survived if an optimal dose of sodium nitrite was injected.Dogs which had received four DL₅₀ of potassium cyanide were kept alive if the treatment with o-aminophenol began at the moment the corneal reflex disappeared.Whereas the intravenous injection of nitrite was found to lower the arterial pressure quickly for a long time, o-aminophenol did not affect the blood pressure in dogs.Briefly presented at a meeting of the Deutsche Pharmakologische Gesellschaft in Bad Nauheim on Oct. 8, 1964 (Kiese andWeger).     

不同首剂量的牛肺表面活性剂对新生儿呼吸窘迫综合征的疗效

目的 通过分析肺表面活性物质（PS）的不同首剂量对新生儿呼吸窘迫综合征（NRDS）的临床疗效。方法 选取2015年4月—2018年3月在平顶山市第一人民医院收治确诊的NRDS 100例作为研究对象,采用随机数字表法分为70 mg/kg剂量组和100 mg/kg剂量组,每组各50例,分别给予注射用牛肺表面活性剂首剂量70、100 mg/kg出生体质量的治疗剂量。比较两组患儿的机械通气时间、氧疗时间、再次应用PS率、住院肺炎发生率及治疗前后的氧分压（pO₂）、二氧化碳分压（pCO₂）、吸入氧浓度（FiO₂）、平均动脉压（MAP）。结果 治疗后,100 mg/kg组患儿的机械通气时间、氧疗时间、再次应用PS率、住院肺炎发生率均低于70 mg/kg组,差异均有统计学意义（P<0.05）,但两组患儿住院时间相比没有显著差异。两组患儿经过治疗后pO₂、pCO₂、FiO₂、MAP均优于治疗前,同组治疗前后比较差异有统计学意义（P<0.05）,其中100 mg/kg组患儿治疗后pCO₂、FiO₂、MAP明显优于70 mg/kg组,差异有统计学意义（P<0.05）,但治疗后两组pO₂差异无统计学意义。结论 注射用牛肺表面活性剂首剂量100 mg/kg出生体质量应用于新生儿呼吸窘迫综合症,能有效显著缩短患儿的氧疗时间及住院时间,降低住院肺炎发生率,具有较好的临床应用价值。     

Formation of cyanide from o-chlorobenzylidene malononitrile and its toxicological significance

Mice received o-chlorobenzylidene malononitrile (CS) by i.p. injection (0.5 LD₅₀) or by aerosol exposure (20,000 mg min^–1 m^–3). Increased excretion of thiocyanate in the urine was observed, indicating a transformation of CS to cyanide in vivo. Determinations of cyanide in whole blood after i.p. administration of CS verified a rapid transformation of the agent to cyanide. A correlation between the time course of cyanide levels and symptoms was observed. Toxicity of injected CS was significantly reduced by pretreatment with thiosulfate, slightly reduced by nitrite and not affected by Co₂EDTA.Thiocyanate excretion, blood cyanide levels and protective effect of antidotes were also evaluated after administration of 0.5 LD₅₀ of malononitrile and potassium cyanide. The importance of cyanide formation for the toxicity of CS is discussed.     

Ferrihemoglobin and kidney lesions in rats produced by 4-aminophenol or 4-dimethylaminophenol

4-Dimethylaminophenol hydrochloride (DMAP), 20 mg/kg i.V., was found to oxidize in rats as much as 50% of the hemoglobin to ferrihemoglobin but did not cause kidney lesions. 4-Aminophenol hydrochloride, 400mg/kg i.V., oxidized only 25% of the hemoglobin and produced large tubular necroses. In highly toxic doses only, e.g., twice the LD₅₀, DMAP also produced tubular necroses.

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Abbreviations Used DMAP 4-Dimethylaminophenol hydrochloride - AP 4-Aminophenol hydrochloride     

The effect of papaverine on local tissue P O 2 and microflow in cat brain cortex

Summary The effect of intracarotid and intravenous administration of papaverine on local tissue P _{O 2} and microflow in the cat's brain surface was studied. Local tissue P _{O 2} was measured with a multiwire surface electrode polaroraphically, and microflow by local hydrogen clearance method.The intracarotid infusions were made for 1, 2 and 5 min with doses of 0.1, 0.2 and 0.5 mg/kg/min papaverine, and the intravenous ones for 5 min with doses of 0.2, 0.5 and 1 mg/kg/min.The continuous intracarotid infusions showed that papaverine in the doses used distinctly increased local tissues P _{O 2} and microcirculation of the brain surface. With the doses applied, systemic arterial pressure (SAP) changed little. It slightly decreased only during the 5 min infusions containing 0.5 mg/kg/min. The duration of the effect increased with increases in the duration of the infusion and of the dose. The maximum duration was observed with 5 min infusions and lasted for 10–15 min after drug administration was discontinued. During the i.v. infusions, tissue P _{O 2} and microflow rose less than with intracarotid ones. No redistribution of capillary flow was observed.     

Efficacy of various dithiol compounds in acute As2O3 poisoning in mice

The efficacy ofdl-dimercaptopropanol (British Anti-Lewisite, BAL),dl-dimercaptopropanesulfonate (DMPS), and meso-dimercaptosuccinic acid (DMS A) was compared in reducing the acute As₂O₃ toxicity in mice. Mice were treated with a single equimolar dose of a dithiol compound (0.7 mmol/kg i.p.) 0.5 or 30 min after the s.c. injection of various doses of As₂O₃. Both DMPS and DMSA were significantly (p<0.05) more effective in mice treated 0.5 min after the poisoning if compared to BAL on an equimolar level. The highest potency ratio (PR) (LD50 with treatment/LD5o without treatment) was found in animals injected with DMSA (PR=8.6). The corresponding value for DMPS was 4.2, and for BAL 2.1, respectively. In animals treated 30 min after poisoning the efficacy of DMPS (PR = 2.6) was similar to the efficacy of DMSA 2.4, both being only slightly superior to BAL 2.O. DMPS and DMSA were found to be much less toxic than BAL. The LD₅₀ of arsenic was 0.057 mmol/kg. The efficacy of BAL, DMPS, and DMSA in reducing the tissue content of arsenic following acute As₂O₃ poisoning was investigated in mice (n=6/group) and guinea pigs (n=3-4/group). The animals were injected s.c. with 0.043 mmol/kg As₂O₃ (containing a tracer dose of⁷⁴As(III)). Thirty minutes later the antidotes were administered A were more effective in reducing the arsenic content of tissues than BAL. Moreover, BAL caused accumulation of the toxicant in the brain. It is concluded that the recommendation of BAL as drug of choice in acute arsenic poisoning needs to be carefully re-evaluated.