Subacute toxicity evaluation in rats exposed to concrete and hwangto building environments

This study examined the potential adverse effects of the subacute exposure of rats to concrete and hwangto building environments. Polycarbonate was used as a comparison. Groups of 10 male rats were exposed to polycarbonate, concrete, or hwangto cages for a 4-week period in summer or winter. During the study period, the clinical signs, mortality, skin temperature, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. The concentration of total volatile organic compounds (VOCs), temperature, and relative humidity in the each cages were also measured. There were no exposure-related effects in any group of the study examined in the summer. The temperature, relative humidity, and the concentration of VOCs in the cages were similar in all groups. However, in the winter study, significant differences in several parameters were detected among the groups. In the concrete group, there was an increase in the clinical signs, a reduction in the body weight gain, food intake, and liver weight, an increase in the lung weight, and an increase in the histopathological alterations in the lung and thymus. Infrared thermal analysis showed that the skin temperature of the rats in the concrete group was lower than that in the polycarbonate group. However, in the hwangto group, there was a decrease in the clinical signs and an increase in the body weight, food intake, and the weights of the heart, lung, spleen, and epididymides. Overall, the 4-week exposure of the rats to the concrete building environment had adverse effects on the clinical signs, skin temperature, body weight, and some organs in the winter but not in the summer. On the other hand, the exposure of hwangto building environment did not have any exposure-related adverse effects on the general health parameters and skin temperature in rats.     

Subacute oral toxicity investigation of selenium nanoparticles and selenite in rats

Selenium (Se) nanoparticles have been proposed as food supplements. However, the particle formulation may exert unexpected toxicity. The aim was therefore to compare toxicity of low doses of Se nanoparticles and the dissolved, ionized Se species selenite. Female rats were dosed orally for 28?d with either: 0.05, 0.5, or 4?mg Se/kg body weight (bw)/day as 20?nm Se nanoparticles or 0.05 or 0.5?mg Se/kg bw/day as sodium selenite. Male rats were dosed 4?mg Se/kg bw/day as Se nanoparticles. Body weight and clinical appearance were recorded throughout the experiment. At necropsy, blood samples were taken for hematological and clinical chemistry analyses; organ weights were recorded. At the high-dose of Se nanoparticles, overt toxicity occurred and the female animals had to be euthanized prematurely, whereas the male animals were reduced in dose. At all doses of Se nanoparticles and at 0.5?mg Se/kg bw/day as selenite, a lower body weight gain as compared to vehicle occurred. Relative liver weight was increased for both Se formulations at 0.5?mg Se/kg bw/day. Creatinine clearance and urinary pH were affected in some Se dosed groups. There were no effects among dosed groups on brain neurotransmitters or on hematological parameters compared with controls. There were no histological changes in the livers of animals exposed to Se nanoparticles or to selenite. Based on effects on body weight and liver weight, selenium nanoparticles and ionic Se exerted similar toxicity. This suggests that a nanoparticle-specific toxicity of Se did not occur.     

Subacute toxicity of all‐trans‐retinoic acid loaded biodegradable microspheres in rats

Biodegradable microspheres containing all‐trans‐retinoic acid (atRA) were prepared previously to enhance the clinical efficacy of atRA for chemoprevention. In this study, subacute toxicity of atRA in sustained release was evaluated after subcutaneous administration of 0, 25, 50, and 100 mg atRA/kg of atRA‐loaded microspheres. After the subcutaneous injection of atRA‐loaded microspheres, the atRA concentration in plasma was maintained in the range of 3.5–25 ng/ml for 2–3 weeks. When 100 mg atRA/kg was administered, the atRA concentration in plasma was maintained at levels greater than 10 ng/ml and severe toxic effects were observed. When the dose of 50 mg atRA/kg was administered, the plasma concentration of atRA was maintained below 10 ng/ml over 3 weeks and only mild signs of toxicity were observed. Therefore, it was concluded that the dosage of atRA‐loaded microspheres should be less than 50 mg atRA/kg for chemopreventive applications against carcinogenesis. Considering recovery from intoxication, the optimum interval for repeated injection of the microspheres was suggested to be over 4 weeks. In addition, it was found that the atRA concentration in plasma should be controlled below 10 ng/ml to minimize toxic effects of atRA. Drug Dev. Res. 59:326–332, 2003. © 2003 Wiley‐Liss, Inc.     

Subacute inhalation toxicity study of synthetic amorphous silica nanoparticles in Sprague-Dawley rats

Synthetic amorphous silica nanoparticles (SiNPs) are one of the most applied nanomaterials and are widely used in a broad variety of industrial and biomedical fields. However, no recent long-term inhalation studies evaluating the toxicity of SiNPs are available and results of acute studies are limited. Thus, we conducted a subacute inhalation toxicity study of SiNPs in Sprague-Dawley rats using a nose-only inhalation system. Rats were separated into four groups and target concentrations selected in this study were as follows: control (fresh air), low- (0.407?±?0.066?mg/m³), middle- (1.439?±?0.177?mg/m³) and high-concentration group (5.386?±?0.729?mg/m³), respectively. The rats were exposed to SiNPs for four consecutive weeks (6 hr/day, 5 days/week) except for control group of rats which received filtered fresh air. After 28-days of inhalation exposure to SiNPs, rats were sacrificed after recovery periods of one, seven and 28 days. Although there were minimal toxic changes such as temporary decrease of body weight after exposure, increased levels of red blood cells (RBCs) and hemoglobin (Hb) concentration, the lung histopathological findings and inflammatory markers in bronchoalveolar lavage (BAL) fluid including polymorphonuclear (PMN) leukocyte, lactate dehydrogenase (LDH), albumin and protein did not show significant changes at any recovery period. The results of this study suggest that the subacute inhalation of SiNPs had no toxic effects on the lung of rats at the concentrations and selected time points used in this study.     

青蒿酯钠静脉注射对犬的亚急性毒性

给犬iv青蒿酯钠每天一次,连续14d,90mg/kg使全部动物中毒死亡,45mg/kg中毒表现明显,2/6犬死亡,22.5mg/kg出现轻度中毒,11.25mg/kg未见明显毒副作用,可视为基本安全剂量。毒性作用的主要症状表现为呕吐、摄食量减少,重者出现粘液血便等;心电图Q-T间期延长,Q-T比值增大;化验及病理检查显示骨髓造血抑制,首先是红系成熟障碍,胆汁淤滞,内脏淤血,45mg/kg以上剂量还出现粒系成熟障碍及心、肝、肾、胃肠道、视网膜等组织实质性损伤及相应的血液学和血液生化变化。血液网织红细胞减少或消失仍是最敏感的指标。停药后28d各种变化基本恢复正常。     

邻苯二甲酸二丁酯对青春期雄性大鼠的毒性研究

目的探讨邻苯二甲酸二丁酯(di-n-butyl phthalate,DBP)对青春期雄性大鼠的系统毒性。方法用DBP灌胃染毒雄性Wistar大鼠8周,剂量分别为250、5001、000 mg/(kg.d)。观察临床症状,动物体重增长,血常规,血清生化,血Zn,解剖及组织病理学等指标。通过剂量-效应关系的分析,求出基准反应(benchmark response,BMR)为10%的基准剂量(benchmark dose,BMD)及95%可信限的下限值(benchmark dose lower bound,BMDL)。结果研究发现具有剂量相关的效应终点有体重、血清尿素氮含量,血清Zn含量,睾丸系数,肾脏系数和肝脏系数,其BMDL分别为408.2,57.7,99.0,263.3,103.1,24.3 mg/(kg.d)。结论DBP对雄性青春期大鼠具有一般毒性。DBP对雄性青春期大鼠一般毒性的最低可观察毒性作用剂量水平(lowest observed adverse effect level,LOAEL)为250 mg/(kg.d),BMD和BMDL分别为42.4和24.3 mg/(kg.d)(根据肝脏系数),同时肝脏系数为最敏感效应指标。研究结果显示,BMDL评价方法较LOAEL方法更为敏感。     

萘普替尼对雄性大鼠睾丸形态结构和附睾精子质量的影响

目的 探究萘普替尼对雄性大鼠睾丸形态结构及附睾精子质量的影响。方法 将30只雄性SD大鼠随机分为30和70 d两组,每组又分为对照组和萘普替尼低、高剂量组（0.75、3.00 mg/kg）,ig给药,每天给药1次,给药体积10 mL/kg。每天进行1次症状观察,每周称量一次体质量,大鼠分别于给药35和70 d后次日处死,肉眼检查各脏器有无异常,检测双侧睾丸质量和横径、附睾尾精子数量和活力,睾丸固定进行组织病理学检查。结果 萘普替尼高剂量组动物均从给药第14天开始,出现腹泻、脱毛、口鼻眼处有红色分泌物,随着给药天数的增加,症状加重;给药70 d组其中1只动物于给药60 d开始出现血尿症状。给药35 d组大鼠从给药21 d开始,给药70 d组从14 d开始,高剂量大鼠体质量明显低于同期对照组（P<0.01）。与对照组比较,给药组雄鼠的双侧睾丸绝对质量和脏器指数、睾丸横径、附睾尾精子数量和活力及睾丸组织病理学检查并未随给药剂量的增加和给药时间的延长而出现明显变化。结论 萘普替尼对雄性大鼠的睾丸组织及精子质量无明显影响。     

Combined repeated dose and reproductive/developmental toxicity screening test of the nitrophenolic herbicide dinoseb, 2-sec-butyl-4,6-dinitrophenol, in rats

In a combined repeated dose toxicity study with reproduction/developmental toxicity screening test, Crj:CD(SD)IGS rats were dosed with dinoseb, 2-sec-butyl-4,6-dinitrophenol, by gavage at 0 (vehicle), 0.78, 2.33, or 7.0 mg/kg bw/day. Six males per group were dosed for a total of 42 days beginning 14 days before mating. Twelve females per group were dosed for a total of 44-48 days beginning 14 days before mating to day 6 of lactation throughout the mating and gestation period. Recovery groups of six males per group and nonpregnant six females per group were dosed for 42 days followed by a 14-day recovery period. No deaths were observed in males of any dose group or in females of the recovery groups. At 7.0 mg/kg bw/day, eight females died and two animals were moribund during late pregnancy, and a significant decrease in body weight gain was found in both sexes. Hematocrit was significantly higher at 0.78 mg/kg bw/day and above in the main group males at the end of administration period. Reduction in extramedullary hematopoiesis in the spleen was significant at 2.33 mg/kg bw/day in the main group females. Sperm analysis revealed a decrease in sperm motility and an increase in the rates of abnormal sperm, abnormal tail, and abnormal head at 7.0 mg/kg bw/day. A number of dams delivered their pups and of dams with live pups at delivery was significantly lowered in the 7.0 mg/kg bw/day group. Based on these findings, the LOAEL for males and NOAEL for females were 0.78 mg/kg bw/day, and the NOAEL for reproductive/developmental toxicity was considered to be 2.33 mg/kg bw/day.     

氢溴酸樟柳碱注射液大鼠单次和重复给药毒性试验研究

目的 通过SD大鼠的单次和重复静脉给药毒性试验,评价氢溴酸樟柳碱注射液的安全性。方法 单次给药毒性试验采用最大耐受量法,观察大鼠的死亡情况和毒性反应。重复给药毒性试验：将大鼠随机分为溶媒对照组和氢溴酸樟柳碱10、50、200 mg/kg剂量组,每组30只,尾iv给药,连续13周,停药恢复4周。进行各项毒理学指标检测。结果 急性毒性试验：氢溴酸樟柳碱注射液在364.5~504.5 mg/kg对大鼠产生明显毒性,症状有给药时尖叫、俯卧、后肢无力、颤抖、抽搐、惊厥、瞳孔散大、尾部发绀等,甚至造成个别动物死亡。重复给药毒性试验：50、200 mg/kg剂量组出现体质量增长减缓,摄食下降,给药后尖叫,鼻端、眼周异常分泌物增多,皮肤脱毛、结痂,耳廓溃疡、缺损,瞳孔散大,尾部发绀,血红蛋白（HGB）、红细胞压积（HCT）、Cl-浓度升高等症状,200 mg/kg剂量组还出现给药后肌张力减退、颤抖、抽搐、呼吸困难、皮下炎性包块等表现。溶媒对照组和200 mg/kg剂量组动物注射部位均出现静脉炎及静脉周围炎,严重程度无差异,停药4周后病变减轻。结论 氢溴酸樟柳碱注射液SD大鼠静脉单次给药的最大耐受量（MTD）为428.8 mg/kg,约相当于临床剂量的2 573倍;重复给药毒性试验未见明显毒性反应剂量（NOAEL）为10 mg/kg,约相当于临床剂量的60倍。     

Acute and subacute oral toxicity of copper oxide nanoparticles in female albino Wistar rats

The extensive use of copper oxide nanoparticles (CuO‐NPs) in various industries and their wide range of applications have led to their accumulation in different ecological niches of the environment. This excess exposure raises the concern about its potential toxic effects on various organisms including humans. However, the hazardous potential of CuO‐NPs in the literature is elusive, and it is essential to study its toxicity in different biological models. Hence, we have conducted single acute dose (2000 mg/kg) and multiple dose subacute (30, 300 and 1000 mg/kg daily for 28 days) oral toxicity studies of CuO‐NPs in female albino Wistar rats following OECD guidelines 420 and 407 respectively. Blood analysis, tissue aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and acetylcholinesterase, superoxide dismutase, catalase, lipid malondialdehyde and reduced glutathione assays, and histopathology of the tissues were carried out. The higher dose treatments of the acute and subacute study caused significant alterations in biochemical and antioxidant parameters of the liver, kidney and brain tissues of the rat. In addition, histopathological evaluation of these three organs of treated rats showed significantly high abnormalities in their histoarchitecture when compared to control rats. We infer from the results that the toxicity observed in the liver, kidney and brain of treated rats could be due to the increased generation of reactive oxygen species by CuO‐NPs.     

Acute and subacute (28-Day) toxicity studies of ionic liquid,didecyldimethyl ammonium acesulfamate,in rats

The aim of this study was to investigate acute and subacute oral toxicity of an ionic liquid, didecyldimethylammonium acesulfamate [DDA][Ace], in rats. The compound tested was classified to the fourth toxicity class with a fixed LD₅₀ cut-off value of 500?mg/kg. Organ pathology induced by [DDA][Ace] in acute experiments included exfoliation of the surface layer of the digestive tract and alveolar septa in lung parenchyma. In a subacute experiment, rats were administered 10, 50, and 100?mg/kg/day [DDA][Ace] for 28 days. Reduced body weight gain and reduced food consumption was observed in mid- and high-dose rats. Statistically significant hematology changes were found mostly in high-dose groups of both sexes: increases in hematocrit, mean corpuscular volume, and mean platelet volume. Statistically significant changes in clinical chemistry parameters included increases in the GGT, SDH, and LDH activity and bilirubin concentration, and decreases in triglycerides, glucose, and inorganic phosphorus concentration. No treatment-related microscopic changes were observed. Under the conditions of this study, the lowest-observed-adverse-effect level of [DDA][Ace] was considered to be 10?mg/kg/day.     

Subacute toxicity of technical fenitrothion in male rats

Male CD-strain rats (100–125 g) received fenitrothion by oral gavage (2.5, 5.0, 10.0 or 20.0 mg/kg/day) for 30 consecutive days. Control animals received equivalent volumes of taurocholate vehicle. Animals were killed at 8, 15, 22 and 30 days during treatment and at 8, 15, 29, 57 and 85 days after terminating treatment. The brain plasma and erythrocyte cholinesterases, hepatic and renal non-specific carboxylesterases were assayed. Serum biochemical markers of hepatic function were measured. Histologically stained sections of liver were examined by light microscopy.Fenitrothion, at doses between 2.5 and 10 mg/kg body wt, caused few observable deleterious effects to male rats except those effects on tissue esterases associated with organophosphorus esters. Only 8 of 36 animals receiving the 20.0 mg/kg dose died, all in the first week of treatment. A dose-dependent decrease in tissue esterase activity was observed which persisted throughout the entire treatment period. Periodic signs of overt toxicity were observed only in animals receiving 20 mg/kg/day. Tissue esterase activities returned to control levels within 1 or 2 weeks of stopping treatment. No significant treatment-related changes were observed by serum biochemistry or by light microscopy.     

Subacute toxicity assessment of carotenoids extracted from citrus peel (Nanfengmiju, Citrus reticulata Blanco) in rats

The mixture of carotenoids extracted from citrus peel (Nanfengmiju, Citrus reticulata Blanco) was tested for subacute oral toxicity. In this study, dose levels of 0, 200, 500 and 2000 mg/kg body weight/day were administered by gavage to 10 Wistar rats/sex/group for 28 days. No statistically significant, dose-related effect on food consumption, food efficiency, body weight gain, clinical signs or ophthalmoscopic parameters was observed in any treatment group. Urinalysis, hematological, blood coagulation and serum biochemical examination as well as necropsy or histopathology showed that no observed adverse effect was found. These findings suggested that the No-Observed-Adverse-Effect Level for the mixture of carotenoids extracted from citrus peel was at least 2000 mg/kg body weight/day.     

阿比朵尔对大鼠的长期毒性

目的:观察阿比朵尔对大鼠的长期毒性反应。方法:96只Wistar大鼠,雌雄各半,随机分成4组,即1200,350和100 mg·kg-1剂量组和对照组,连续灌胃给药4周,按常规方法观察动物一般状况、体重、摄食量、血液学、血液生化、脏器重量系数及组织病理学改变。结果:阿比朵尔未引起动物死亡。给药期:高剂量组雌鼠第1-4周体重明显低于对照组,并有6只动物陆续出现明显掉毛;高剂量组雄鼠第2-4周体重明显低于对照组,并有4只动物陆续出现明显掉毛;其他指标与对照组比较无明显差异。低剂量组和中剂量组各项指标与对照组比较均无明显差异。恢复期:高剂量组雌鼠第1周体重仍明显低于对照组,其他各剂量各项指标与对照组比较均无明显差异。结论:大鼠口服阿比朵尔4周,350 mg·kg-1为安全剂量,1 200 mg·kg-1对大鼠生长有可逆性抑制作用。     

Subacute toxicities and toxicokinetics of DA-8159, a new phosphodiesterase type V inhibitor, after single and 4-week repeated oral administration in rats

The subacute toxicities (10 male and 10 female rats at each dose) and the toxicokinetics (5 male rats at each dose) of DA-8159, a new phosphodiesterase type V (PDE V) inhibitor, were evaluated after single (at day 1) and 4-week (at day 28) oral administration of the drug at doses of 0 (to serve as a control), 20, 80 and 320 mg/kg/day to rats. DA-8159 showed a decrease in body weight gain, clinical signs such as chromodacryohaemorrhoea, ptosis and decreased locomotor activity, an increase in WBC number, changes in parameters related to RBCs, an increase in organ weight of the liver, spleen and lung, and finally microscopic lesions such as cholangiofibrosis and inflammatory cell infiltration in the liver, alveolar macrophage accumulation, and inflammatory cell infiltration in the lung, an increase in bone marrow density and extrahaematopoiesis in the spleen. These changes were observed mainly at a dose of 80 mg/kg or above. While some changes were observed at a dose of 20 mg/kg, these changes were non-specific and transient since this were also observed in control rats. In addition, there was no dose-dependency in these changes. Based on these results, the NOAEL (No-Observed-Adverse-Effect-Level) for DA-8159 in rats was estimated to be 20 mg/kg/day, and the target organs were determined to be liver, bone marrow, spleen, lung and blood cells. After a 4-week oral administration, accumulation of DA-8159 was evident at a dose of 20 mg/kg/day, but was not considerable at toxic doses (80 and 320 mg/kg/day). After a single oral administration, the dose-normalized area under the plasma concentration-time curve from time zero to the last measured time, 24 h, in plasma (AUC(0-24 h)) was significantly different among the three doses (the AUC(0-24 h) based on 20 mg/kg/day was 2.33, 7.00 and 4.19 microg h/ml for 20, 80 and 320 mg/kg/day, respectively). Similar results were also obtained from DA-8164, a metabolite of DA-8159; the AUC(0-24 h) of DA-8164 after dose-normalized to 20 mg/kg/day of DA-8159 were 2.74, 5.00 and 1.68 microg h/ml, respectively.     

Phenthoate toxicity: cumulative effects in rats

This study was designed to provide information on the cumulative effects of phenthoate, an organophosphorus insecticide. Male rats were given the test compound orally 6 days/week for a minimum of 10 weeks and until the cumulative LD50 (CLD50) remained constant for 3 consecutive weeks. The oral LD50 value for phenthoate in rats was highest (116 mg/kg) in groundnut oil followed by dimethylsulfoxide (DMSO) and alcohol. The animals with lesser weight were more susceptible than the heavier animals. Rats receiving 2.5 to 10 mg/kg phenthoate for 13 weeks showed varying decreases in weights of liver, heart, spleen, brain, testes and adrenals. At 40 mg/kg, none of the animals survived. The CDL50 for 13 weeks was 12 mg/kg with a cumulative toxicity factor of 6.3. The compound has been rated as a moderately hazardous one.     

Toxicological assessments of an ethanol extract complex of Descurainia sophia and Peucedanum praeruptorum: Subacute oral toxicity and genotoxicity studies

An ethanol extract complex of Descurainia sophia seeds and Peucedanum praeruptorum roots, called BP10A, has antitumor potential against colorectal cancer. In the present study, we evaluated the 28-day oral toxicity and the genotoxicity of BP10A. The subacute toxicity test was done through oral administration to mice. ICR mice (n = 10) received daily oral BP10A doses of 0, 500, 1000 and 2000 mg/kg for 28 consecutive days. During administration, general clinical signs, food consumption, organ weights, and hematologic, biochemical and histopathological parameters in male and female mice were assessed. No significant adverse effects up to the highest dose (2000 mg/kg) were found. The genotoxicity was evaluated using a battery of tests, including an in vitro bacterial reverse mutation (Ames) test, an in vivo micronucleus test using bone marrow cells in ICR mice and a chromosomal aberration test using CHL/IU cells. BP10A did not show any genotoxic signs in the Ames (up to 5000 μg/plate), micronucleus (up to 5000 mg/kg) and the chromosomal aberration tests (550-1750 μg/mL). Therefore, BP10A was considered safe based on the subacute toxicity and genotoxicity results, indicating that it is a useful pharmaceutical material with no adverse toxicity.     

Assessment of dose-dependent reproductive toxicity of diclofenac sodium in male rats

Diclofenac sodium is widely used in the non-steroidal anti-inflammatory drug in the treatment of pain and inflammation. It is also particularly associated with its adverse effects on avian fauna and linked to environmental issues. The present study was aimed to assess the dose-dependent toxicity of diclofenac sodium on a male reproductive system of rats. Four groups of healthy adult fertile male rats were administered with saline (control) or 0.25?mg/kg, 0.50?mg/kg and 1.0?mg/kg of diclofenac sodium, respectively for 30 days. Alterations in body and organ weight, sperm and testicular cell population dynamics, serum biochemistry, histopathology, and hematology were investigated as per aimed objectives. Diclofenac sodium treatment significantly (p?≤?0.001) reduced weights of testis, epididymis, ventral prostate and seminal vesicle. Sperm count, sperm density (in epididymis and testis), sperm motility and testicular cell population dynamics were lowered in a dose-dependent manner. Administration of diclofenac exhibited varying degrees of degeneration testis, abnormal histo-architectures, and shrinkages in seminiferous tubules, particularly in higher doses. Diclofenac sodium treatments also altered hepatic and renal function parameters significantly. In conclusion, it may claim that diclofenac sodium treatment altered reproductive metabolic status, androgenic activities and histo-architecture of the testis of male rats and induced hepatotoxicity and renal toxicity.     

Subchronic oral toxicity of strychnine in rats

In recent years strychnine has been used for the treatment of nonketotic hyperglycinemia, a rare metabolic disease in infants. Since no information on repeated dose toxicity of this drug was available, a subacute oral toxicity study in rats was conducted. Strychnine hydrochloride was administered orally to rats for 4 weeks in aqueous 0,2 % solution. The study showed no organ and tissue damage or functional disorders. The difficulty to conduct meaningful repeated-dose toxicity studies with drugs exhibiting potent pharmacological actions and a steep dose-effect curve are discussed.     

Malathion-induced testicular toxicity in male rats and the protective effect of vitamins C and E

Sexually mature male Wistar rats (weighing 300–320 g and each group 6 animals) were given malathion (27 mg/kg; 1/50 of the LD₅₀ for an oral dose) and/or vitamin C (200 mg/kg) + vitamin E (200 mg/kg) daily via gavage for 4 weeks. The sperm counts, sperm motility, sperm morphology, FSH, LH, and testosterone levels, and histopathological changes in the testes of these rats, were investigated at the end of the 4th week. By the end of 4th week, rats given malathion alone, or in combination with vitamins C and E, had significantly lower sperm counts and sperm motility, and significantly higher abnormal sperm numbers, than the untreated control rats. The rats given malathion alone or in combination with vitamins also had significantly lower plasma FSH, LH and testosterone levels than the control rats. Co-treatment of malathion-exposed rats with vitamins E and C had a protective effect on sperm counts, sperm motility and abnormal sperm numbers, but not on plasma FSH, LH and testosterone levels. Light microscopic investigations revealed that 4 weeks of malathion exposure was associated with necrosis and edema in the seminiferous tubules and interstitial tissues. Degenerative changes in the seminiferous tubules were also observed in the rats which received malathion and supplemented with vitamins C and E, but milder histopathological changes were observed in the interstitial tissues. Thus, it appears that vitamins C and E ameliorate malathion testicular toxicity but are not completely protective.