Salinity-mediated changes in hematological parameters,stress, antioxidant responses,and acetylcholinesterase of juvenile olive flounders (Paralichthys olivaceus)

The purpose of this study was to confirm the limit of salinity tolerance in juvenile olive flounders (Paralichthys olivaceus) by changes in blood parameters, AChE, antioxidant and stress responses. The P. olivaceus (mean weight 38.8 ± 4.2 g and mean length 16.4 ± 1.2 cm) were exposed to different concentrations of salinity (seawater, 16, 8, 4, 2, and 0 psu) for 2 weeks. Plasma osmotic pressure was significantly decreased in the P. olivaceus at 0 psu. Hematological parameters such as hematocrit and hemoglobin were significantly decreased in the P. olivaceus at low salinity. Plasma components also changed significantly in the low salinity environment. As a stress indicator, cortisol was significantly increased at low salinity. SOD and GST antioxidant responses, were significantly increased. GSH level in the liver was significantly increased, whereas a significant decrease was observed in the gill GSH level. AChE was significantly increased in P. olivaceus at low salinity. The results of this study indicate that exposure to salinities lower than 8 psu leads to changes in hematological parameters, neurotransmitter, antioxidant and stress responses of P. olivaceus.     

Toxic effects of juvenile sablefish,Anoplopoma fimbria by ammonia exposure at different water temperature

Juvenile sablefish, Anoplopoma fimbria (mean length 17.1 ± 2.4 cm, and mean weight 75.6 ± 5.7 g) were used to evaluate toxic effects on antioxidant systems, immune responses, and stress indicators by ammonia exposure (0, 0.25, 0.75, and 1.25 mg/L) at different water temperature (12 and 17 °C) in 1 and 2 months. In antioxidant responses, superoxide dismutase (SOD) and catalase (CAT) were significantly increased by ammonia exposure, whereas glutathione (GSH) was decreased. In immune responses, lysozyme and phagocytosis activity were significantly increased by ammonia exposure. In stress indicators, plasma glucose, heat shock protein 70 (HSP 70), and cortisol were significantly increased. At high water temperature (17 °C), alterations by ammonia exposure were more distinctly. The results of this study indicated that ammonia exposure can induce toxic effects in the sablefish, and high water temperature can affect the ammonia exposure toxicity.     

Dietary vitamin C reduced mercury contents in the tissues of juvenile olive flounder (Paralichthys olivaceus) exposed with and without mercury

A 2 × 3 factorial design was employed to evaluate the effects of dietary vitamin C (l-ascorblyl-2-monophosphate, C2MP) levels on growth and tissue mercury (Hg) accumulations in juvenile olive flounder, Paralichthys olivaceus. Six experimental diets with two levels of mercuric chloride (0 or 20 mg HgCl₂/kg diet) and three levels of vitamin C (0, 100, or 200 mg C2MP/kg diet) were added to the basal diet. At the end of 6 weeks feeding trial, in presence or absence of dietary Hg, fish body weight gain, specific growth rate, feed efficiency, protein efficiency ratio and whole body lipid content were increased in a dose-dependent manner as dietary vitamin C level increased in the diets. Interestingly, fish fed 100 or 200 mg C2MP/kg diets showed significant interactive effects on reducing Hg content in kidney tissue. These results revealed that dietary vitamin C as 100 or 200 mg C2MP/kg diet had protective effect against Hg accumulation in juvenile olive flounder.     

槟榔碱提神效果及急性毒性作用研究

目的研究槟榔主要活性物质槟榔碱的提神及急性毒性作用,为槟榔食用安全提供参考依据。方法将昆明小鼠随机分成3组．腹腔注射各浓度的槟榔碱溶液30s后再注射苯巴比妥钠溶液,记录小鼠抗睡眠时间,同时以无菌生理盐水及同浓度的天竺葵作对照。采用霍恩法进行槟榔碱的急性毒性试验,计算其LD50并判定其毒性等级;解剖中毒小鼠,观察其病理变化。结果槟榔碱的抗睡眠时间随浓度的增大而增长,0．5mg的槟榔碱抗1．5×10^-4g苯巴比妥钠溶液引起的睡眠时间可达38min;槟榔碱的LD50是430mg／kg体重,95％可信限为295-626mg／kg体重,属于中等毒性。中毒死亡小鼠的肝脏稍微肿大,脾脏颜色变深、体积变大,肺部颜色略变深、有出血现象、肠内有空泡样。结论槟榔碱有抗苯巴比妥钠催眠的显著作用,是一种中等毒性物。     

通脉益智颗粒的抗炎镇痛作用及急性毒性研究

目的 研究通脉益智颗粒的抗炎镇痛作用及急性毒性,探讨其抗炎作用机制,为该药的临床用药和进一步研发提供实验依据.方法 选择清洁级癌症研究所（ICR）小鼠240只为受试对象,按体重分为阴性对照组（0.9％氯化钠注射液）、阿司匹林组（0.2 g/kg）、通脉益智高剂量组（14.4 g生药/kg）、中剂量组（7.2g生药/kg）、低剂量组（3.6g生药/kg）.采用二甲苯所致小鼠耳肿胀和冰醋酸致小鼠腹腔毛细血管通透性增高法研究通脉益智颗粒的抗炎作用;采用冰醋酸致小鼠扭体反应和小鼠热板致痛实验来研究通脉益智颗粒的镇痛作用.采用最大耐受量试验进行急性毒性实验,通脉益智颗粒组给予最大给药浓度、给药体积灌胃,与阴性对照组对照比较,连续观察14 d,观察小鼠的一般状况、死亡数及主要脏器变化.结果 与阴性对照组相比,通脉益智高剂量组及阿司匹林组抑制效果明显[吸光度：（0.7±0.4）、（0.6±0.3）比（1.2±0.5）]（P＜0.05）.通脉益智中、高剂量组及阿司匹林组的耳肿胀度明显低于阴性对照组[（5.8±2.8）、（5.4±3.9）、（4.8±2.1）g比（9.2±2.5）g]（P＜0.05或P＜0.01）.通脉益智低、中、高剂量组及阿司匹林组的耳肿胀率明显低于阴性对照组[（50±25）％、（46±21）％、（43±30）％、（38±16）％比（72±17）％]（P＜0.05或P＜0.01）.通脉益智中剂量组给药后45、90、135 min的痛阈值均明显高于阴性对照组[（26.2±4.5）s比（16.6±4.4）s、（24.7±4.4）s比（14.9±4.8）s、（20.6±3.0）s比（16.1±4.8）s]（P＜0.05或P＜0.01）;通脉益智高剂量组给药后45、90 min的痛阈值明显高于阴性对照组[（23.6±5.0）、（20.4±6.5）s]（P ＜0.05或P＜0.01）;阿司匹林组给药后45、90、135 min的痛阈值均明显高于阴性对照组[（30.8±7.5）、（27.5±8.6）、（22.6±4.4）s]（P＜0.01）.通脉益智中、高剂量组与阿司匹林组的潜伏期、扭体次数与阴性对照组比较,差异均有统计学意义[潜伏期：（6.8±0.6）、（6.6±1.7）、（7.2±1.3） min比（4.8±2.0）min;扭体次数：（23±9）、（22±7）、（16±9）次比（33±10）次]（P＜0.05或P＜0.01）.MTD试验中,以最大给药浓度（4 g生药/ml）、给药体积（0.03 ml/g）1 d 1次灌胃小鼠,连续观察14 d,小鼠未出现死亡.通脉益智组和阴性对照组雌雄性小鼠给药14 d后体重与给药前体重比较,差异有统计学意义[通脉益智组：（30.6±2.7） mg比（23.5±1.4）mg、（33.0±0.9） mg比（22.8±1.3）mg;阴性对照组：（29.8±2.7）mg比（22.7±1.5）mg、（34.0±1.6）mg比（23.2±1.1）mg] （P ＜0.01）.通脉益智颗粒的最大耐受量为120 g生药/（kg＆#183;d）,相当于60 kg人临床用量的150倍.结论 通脉益智颗粒具有一定的抗炎镇痛作用,且无明显急性毒性反应,提示通脉益智颗粒在临床推荐剂量下使用是安全的.     

Thirty-day rat toxicity study reveals reversible liver toxicity of mifepristone (RU486) and metapristone

Objective: Mifepristone (RU486) is an oral first-line contraceptive used by hundreds of millions of women, and recently it was tested for anticancer activity in both genders worldwide. We are developing metapristone (the N-monodemethyl RU486) as a potential metastasis chemopreventive. The present acute and 30-d subacute toxicity study aimed at examining and compared in parallel the potential toxicity of the two drugs.

Methods: The single-dose acute toxicity and 30-d subacute toxicity studies were conducted in mice and rats, respectively, by gavaging metapristone or mifepristone at various doses. Blood samples and organs were collected for blood chemistry, hematology and histology analyses.

Results: Oral mifepristone (3000?mg/kg) caused 30% and 40% death in female and male mice, respectively, within 15 h post-dosing. In comparison, the same dose of metapristone produced 30% acute death in males only. Thirty-day oral administration of the two drugs to rats (12.5, 50 and 200?mg/kg/day) caused reversible hepatotoxicity that only occurred at 200?mg/kg/day group, evidenced by the elevated liver enzyme activity and liver organ weight.

Conclusion: The present study, for the first time, reveals reversible hepatotoxicity in rats caused by the 30-d consecutive administration at the high dose, and warns the potential hepatotoxicity caused by long-term administrations of high doses of mifepristone or metapristone in clinical trials but not by the acute single abortion doses.     

Effects of waterborne acephate exposure on antioxidant responses and acetylcholinesterase activities in Synechogobius hasta

The present study was conducted to determine the 24, 48, 72, and 96‐h median lethal concentration (LC50) of acephate and investigate the antioxidant response and acetylcholinesterase (AChE) activities in liver, gill, and spleen of Synechogobius hasta exposed to 0 (control), 5, and 10 mg/L acephate, at the fixed interval time of 24, 48, 72, and 96 h, respectively. LC50 value was 60.83 mg/L at 24 h, 51.36 mg/L at 48 h, 47.07 mg/L at 72 h and 40.13 mg/L at 96 h, respectively. Dismutase (SOD), catalase (CAT), AChE activities, and malondialdehyde (MDA) levels in these tissues for the control remained stable over the exposure period. However, for the two tested groups, tissue‐, dose‐, and time‐dependent responses of these parameters were observed in S. hasta. In general, hepatic SOD and CAT activities were significantly inhibited at 24 h, activated, and increased at 48 h, but again inhibited from 48 to 96 h in fish exposed to the two tested concentrations. Hepatic MDA levels of fish for the two tested concentration peaked at 48 h, significantly higher than the control. Hepatic AChE activity was inhibited at 24 h, peaked at 48 h, and then declined at 72 h for the two tested groups. For gills, the highest SOD and CAT activities for the two tested groups were observed at 48 h, higher than the control. AChE activities for the two tested groups were significantly inhibited at 24 h, but activated at 48 h. At 96 h, AChE activities among the treatments showed no significant differences. Gill MDA levels at 48 h for the tested groups were significantly higher than the control, but showed no significant differences at 24 and 72 h among the treatments. In spleen, SOD and CAT activities at 48 h for the two tested groups were significantly higher than those in the control, but at 96 h the vice versa was true. Spleenic AChE activities and MDA levels for the two tested groups were inhibited at 24 h, activated at 48 h, and then were again inhibited at 72 h. Based on these observations earlier, the results obtained in our study will have important toxicological implications for waterborne acephate pollution and, meantime, provide the basis for the effective risk assessment of acephate in water environment and appropriate safety recommendations for fish. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2013.     

退热贴的急性毒性、刺激性及过敏性试验观察

目的:观察退热贴的急性毒性、刺激性及过敏性,为其临床应用安全性提供依据.方法:通过一般情况观察与组织病理学检查综合观察退热贴1次给药经豚鼠完整皮肤及破损皮肤吸收后所产生的急性毒性反应和刺激性反应,及豚鼠皮肤重复接触退热贴后的过敏反应情况.结果:退热贴对实验动物无急性毒性;对豚鼠完整皮肤及破损皮肤均无刺激性作用;豚鼠皮肤重复接触不引起皮肤过敏反应.结论:研究结果提示退热贴在临床应用中有较好的安全性.     

Synthesis, acute toxicity, and analgesic activity of new derivatives of pyrrole

Ten pyrrole derivatives (including six new compounds) were synthesized and evaluated as potential platform for analgesic agents' development. Acute intraperitoneal toxicity and analgesic activity studies (acetic acid writhing test) were performed on mice with acetylsalicylic acid used as a reference substance. Products 3c, 3d, 3e, and 3h exhibited a dose-dependent activity demonstrating 1.5 to 2.5-fold better protections than the reference. The most prospective compounds comprised salicylic acid moieties, whose 4-substituted derivatives were related to lower acute toxicity and considerable activity. 4-[3-(Ethoxycarbonyl)-2-methyl-5-(3,4-dimethoxy-phenyl)-1H-pyrrol-1-yl]-2-hydroxy-benzoic acid 3c was pointed out as the most prospective substance due to its lower acute toxicity (378 mg/kg body weight, intraperitoneally) and highest analgesic activity (up to 89.3% protection) in a dose range of 1/10 to 1/40 parts of LD(50).     

Behavior evaluation of rainbow trout (Oncorhynchus mykiss) following temperature and ammonia alterations

In the study, we assessed how acute changes in water temperature and dissolved ammonia concentration can affect the swimming behavior pattern of rainbow trout (Oncorhynchus mykiss). The behavior was analyzed in three different stages: 1) increase stage, (where temperature and ammonia concentration increase during this step, respectively); 2) unchanged stage, (where levels of both factors do not change during this stage); 3) reduction stage, (where ammonia concentration and temperature during this stage are reduced), respectively. The results showed that both factors significantly changed the swimming pattern of the rainbow trout. There were significant differences in swimming parameters (distance from the center, swimming speed, total movement and the average of angular changes of movement) of treated fish in the comparison between treatments, and with the control group. The changes in the swimming pattern of fish in response to physicochemical parameters of water were confirmed to be a good tool in ecotoxicological studies.     

The effect of polymorphisms of gamma-glutamyl hydrolase (GGH) gene on methotrexate-induced toxicity in acute lymphoblastic leukemia

Context: Acute lymphoblastic leukemia patients show differences in methotrexate-induced toxicity after treatment with this anti-cancer drug. Pharmacogenetics is an important determining factor for toxicity diversity. Objective: In this study, the effect of +452 CT and ? 401CT polymorphisms of Gamma-glutamyl hydrolase (GGH) gene on methotrexate serum levels and its associated toxicity in patients with acute lymphoblastic leukemia was assessed. Furthermore, the frequency of the above polymorphisms was investigated for the first time in Iran. Material and methods: The prevalence of these polymorphisms was assessed in 83 Iranian patients with ALL using PCR and RFLP. The relationship between the polymorphism and serum methotrexate levels and its toxicity was estimated by calculating the Odds Ratio. Results: No correlation was found between +452CT polymorphism and serum levels of methotrexate and methotrexate-related toxicity. ?401CT polymorphism was found to be correlated with methotrexate-related toxicity leading to thrombocytopenia (95% CI?=?0.009–0.019, odds ratio?=?0.265) and leukopenia (95% CI?=?0.021–0.042, odds ratio?=?2.182) in consolidation phase of the treatment. Discussion: C allele polymorphism of ?401?C/T allele is a risk factor of leukopenia and thrombocytopenia in patients treated with methotrexate. Moreover, our results suggested that the T allele had a supporting role in prevention of thrombocytopenia. Conclusion: Evaluation of patients for methotrexate-related polymorphism of GGH gene may be useful to determine the appropriate dose of methotrexate and reducing its toxic side effects.     

参菊洗剂的抗过敏、止痒作用及急性毒性研究

目的:探讨参菊洗剂抗过敏、止痒作用及可能的机制,并进行急性毒性实验研究。方法:采用2,4-二硝基氯苯(DNCB)致小鼠迟发型超敏反应模型,观察0.054、0.108、0.216 g·mL^-1参菊洗剂抗过敏作用。采用右旋糖酐致小鼠全身瘙痒、磷酸组胺致豚鼠局部瘙痒2种模型,观察0.054、0.108、0.216 g·mL^-1参菊洗剂对小鼠、豚鼠瘙痒反应的影响,并测定炎症小鼠血清超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)等炎症因子的水平,探讨参菊洗剂止痒机制。采用0.108、0.324、0.540 g·mL^-1参菊洗剂进行小鼠口服给药急性毒性实验。结果:参菊洗剂各剂量组可不同程度抑制DNCB所致的小鼠迟发型超敏反应,高剂量组能明显升高胸腺指数及脾指数,显著减少右旋糖酐引起的小鼠瘙痒发作次数和持续总时间,提高血清SOD活性(P<0.05),降低血清MDA、TNF-α水平(P<0.05),抑制磷酸组胺致豚鼠局部瘙痒,提高致痒阈。小鼠未出现中毒反应和死亡。结论:参菊洗剂外用具有抗过敏、止痒作用,其止痒机制可能与抑制脂质过氧化及清除自由基、抑制炎症因子的合成与释放有关。小鼠口服给药基本无毒。     

葡萄糖酸铜的急性毒性和药代动力学

应用原子吸收光谱法，以硫酸铜作对照，对葡萄糖酸铜的急性毒性和在家兔体内的组织分布及其药代动力学进行了实验研究。结果表明，葡萄糖酸铜口服毒性小，静注毒性较大，但两者的毒性均较硫酸铜为小，而且葡萄糖酸铜吸收后，在家兔体内５种脏器中铜含量均较硫酸铜高。此两种药物口服均为开放式－宝模型，葡萄糖酸铜较硫酸铜达峰时间短，半衰期短，消除速度快，维持时间短，两者在家兔体内代谢过程不一致。     

Effect of temperature on heavy metal toxicity to juvenile crayfish, Orconectes immunis (Hagen)

The acute toxicity of four selected heavy metals to juvenile crayfish Orconectes immunis (Hagen) (1-2 g wet body wt. each) at room temperature increased in the following order: cadmium (x3) < copper (x10) < zinc (x2) < lead. The toxicity of these metals to crayfish acclimated at 17, 20, 23/24, and 27 degrees C increased with temperature (by 7-20% between 20 and 24 degrees C and 14-26% between 20 and 27 degrees C) as judged by the lowering of LT(50) (time to kill 50% of test animals at a fixed concentration) values. A 4 degrees C rise in temperature (from 20 to 24 degrees C), which increased the toxicity of copper by about 7%, increased the rate of oxygen consumption by about 34%. Heavy metals inhibited the rate of oxygen consumption at all temperatures. In 20 degrees C-acclimated crayfish, copper caused about 17% inhibition of oxygen consumption compared to about 7-12% by other metals including the most toxic cadmium. A 3-4 degrees C rise in temperature tripled the inhibitory effect of copper (20%), cadmium and zinc (26 and 18%, respectively), but not of lead, on oxygen consumption. A 7 degrees C-rise in temperature (from 20 to 27 degrees C) increased the inhibitory effect of heavy metals, including lead, on oxygen consumption by up to 54% in the case of copper. The data indicate that rising global temperatures (currently 0.60 degrees C) associated with climate change can have the potential to increase the sensitivity of aquatic animals to heavy metals in their environment.     

Toxic effects of imidacloprid on adult loach (Misgurnus anguillicaudatus)

The present investigation was aimed to assess the effects of imidacloprid on the survival, genetic materials, hepatic transaminase activity and histopathology of loach (Misgurnus anguillicaudatus). The values of LC₅₀ (24, 48, 72 and 96 h) of imidacloprid were 167.7, 158.6, 147.9 and 145.8 mg/L, respectively, and the safety concentration was 42.55 mg/L. The erythrocyte micronuclei assays and the comet assay results showed that imidacloprid had genetic toxic effect on the loach erythrocytes. To assess the physiological and biochemical damage caused by imidacloprid, the activities of hepatic glutamic-pyruvic transaminase (GPT) and glutamic-oxalacetic transaminase (GOT) were measured and their values declined in treatment groups. Histological examination of testis revealed that imidacloprid treatment resulted in disorganized lobules and cysts structures. In the present work, we also investigated the joint toxicity of pesticides commonly used in paddy fields (imidacloprid and lambda-cyhalothrin) on M. anguillicaudatus, and confirmed that a synergistic effect existing in the binary mixtures. The results of our study provide relevant and comparable toxicity information that are useful for safety application of pesticides.     

Protective effect of a novel antioxidant non-steroidal anti-inflammatory agent (compound IA) on intestinal viability after acute mesenteric ischemia and reperfusion

Reactive oxygen species play an important role in the basic pathophysiology of ischemia-reperfusion injury. We investigated whether the administration of a novel non-steroidal anti-inflammatory compound with antioxidant properties, the compound [5-(2-amino-ethylamino)-1-phenyl-2-pentanone] (compound IA), has a beneficial effect on the repair process of the intestinal mucosa after transient mesenteric ischemia in a randomized blind trial. Six groups of rats were subjected to a model of 60 min of intestinal ischemia that was produced by occluding the superior mesenteric artery. At the end of ischemia, compound IA was administered intravenously and the clamp was removed allowing reperfusion. At 60 min after reperfusion, animals were sacrificed and a 10 cm section of terminal ileum was resected. The outcome was evaluated by histopathologic assessment, measurement of polymorphonuclear leukocytes and the extent of lipid peroxidation measuring the small intestine tissue malondialdehyde. After 1 h of reperfusion, the mucosal damage was less in IA-treated rats compared with the control group. Moreover, the number of polymorphonuclear leukocytes in intestinal mucosa was significantly lower in IA group. Compound IA resulted in a statistically significant reduction of the concentration of small intestine tissue malondialdehyde, compared to those of controls. Administration of compound IA decreased the mucosal damage in rats that were subjected to 60 min of ischemia followed by 60 min of reperfusion. The mechanism of compound IA action is considered to be mediated via its potent antioxidant, free radical scavenging activities and inhibition of polymorphonuclear leukocytes infiltration.     

The acute oral and intravenous toxicity of p-aminopropiophenone (PAPP) to laboratory rodents

The acute toxicity of p-aminopropiophenone (PAPP) to three species of laboratory animals has been investigated using solutions in dimethylsulphoxide (DMSO) for intravenous and oral (intragastric) administration. In addition, methaemoglobinaemia and Heinz-body haemolytic anaemia are described.     

罗红霉素注射液的急性毒性及致突变性研究

目的 初步评价罗红霉素注射液的基础毒性和特殊毒性。方法 进行了急性毒性试验、骨髓细胞微核试验和精子畸形试验。结果 其LD50为492．04mg／kg，无明显的致畸突变作用。结论 罗红霉素注射液对小鼠骨髓细胞和雄性生殖细胞无致突变作用。     

7种化合物细胞毒性与小鼠急性毒性的相关性研究

目的：为减少实验动物的使用,利用化学物质的体外细胞毒性数据对体内急性毒性进行预测。方法：MTT比色法检测7种新化学实体对CHL细胞的毒性作用,利用RC（Registry of Cytotox-icity）预测模型对急性毒性LD50值进行预测,并使用小鼠急性毒性上下法进行验证。结果：各化合物（1～7）细胞毒性IC50值分别为0.43、0.49、0.18、0.67、3.03、1.68、1.79mg/mL;根据RC预测模型,急性毒性LD50的预测值分别为2376.4、2478.3、1574.8、2087.6、4897.3、3331.8、3300.7mg/kg。经上下法检测,4号化合物的LD50值为1634.0mg/kg,其余6种化合物的LD50值均大于2000.0mg/kg。分别以预测值和实测值为依据对化合物毒性进行分级,二者相比,仅3号和4号化合物毒性分级略有差异,其它5种化合物的毒性分级基本一致。结论：体外细胞毒性数据可用来预测体内急性毒性,减少实验动物使用。     

Evaluation of the acute oral toxicity class of tricentric chromium(III) propionate complex in rat

Chromium(III) is an essential element for carbohydrate and lipid metabolism, and various chemical forms of this element are widely used in dietary supplements. Of particular interest is [Cr₃O(O₂CCH₂CH₃)₆(H₂O)₃]⁺ cation (CrProp), that has been proposed as an alternative source of Cr. However, its safety has not been studied completely. In this study, we evaluated the acute toxicity class of CrProp in Wistar rats applying the OECD 423 procedure. Male and female Wistar rats (n = 12, 6 ♀ and 6 ♂) were given by gavage either a single dose of CrProp 2000 mg kg⁻¹ body mass or equivalent volumes of distilled water, and fed Labofeed B diet, and observed carefully for 14 days, than sacrificed to collect samples for biochemical and histologic examination. No death cases were detected, no major abnormalities in animal behaviour, body mass gains, gross organ histology, and blood morphology, and biochemistry were observed, except some changes of liver mass and the activity of ALT in female rats. The results demonstrate that LD₅₀ of CrProp is greater than 2000 mg kg⁻¹ when administrated orally to rat, thus this compound appears to be belong the fifth category in the GHS system or the fourth class (“unclassified”) in the EU classification system.