盐酸西部曲明对小鼠生殖力和着床前后胚胎发育的影响

目的　评价减肥新药盐酸西部曲明对♀亲代动物的生殖毒性和受精卵着床前的发育毒性。方法　持续饮水内给药 ,♂小鼠交配前给药 8周并持续给药至交配成功处死之前 ;♀小鼠交配前给药 2周并持续给药至妊娠d6。设 32、2 83、0 .2 5mg·kg-1·d-13个剂量组及 1个阴性对照组 ,观察亲代动物的一般状况、交配、受孕和妊娠 ,胎仔的着床、存活、体长、体重、外观、内脏和骨骼畸形等检测指标。结果　除相当于人预期摄入量 12 8倍的高剂量引起了亲代雄鼠体重减轻外 ,亲代和子代小鼠均未见其他毒性反应。结论　未见盐酸西部曲明对亲代有生殖毒性和对子代有发育毒性。     

The effects of tetrathiomolybdate (TTM, NSC-714598) and copper supplementation on fertility and early embryonic development in rats

Based on its ability to chelate copper, TTM is being studied as an antiangiogenic agent for cancer therapy. The purpose of this study was to evaluate the toxicity of TTM and the protection of copper supplementation on the reproductive capability of male and female CD rats. Doses of 0, 1, 4, and 12 mg/kg/day with copper supplementation (110 mg/kg of diet) were given by gavage. There were no effects on the estrous cycle or reproductive indices, or maternal toxicity in any female dose group. Male rats given 12 mg/kg/day showed significant decreases in body weight gains and food consumption, and anemia. Serum ceruloplasmin levels were dose-dependently decreased in all male dose groups. Reduced epididymal weights, sperm counts, and sperm motility, sperm morphologic abnormalities and histopathologic changes in testis and epididymis occurred only at 12 mg/kg/day. Dietary copper supplementation prevented the adverse sperm effects produced by 12 mg/kg/day of TTM.     

Evaluation of the toxic potentials of a new camptothecin anticancer agent CKD-602 on fertility and early embryonic development in rats

This study examined the potential adverse effects of a new camptothecin anticancer agent, CKD-602, on the fertility and early embryonic development of Sprague-Dawley rats. Ninety-six rats of each gender were divided into four groups: three treatment groups and a control group. CKD-602 was administered intravenously to male rats at 0, 4.7, 14, and 42 microg/kg from 63 days prior to mating until the end of the mating period, and to female rats from 14 days before mating until day 6 of gestation. All the males were sacrificed after the end of the 14-day mating period, while all the females were subjected to a caesarean section on day 15 of gestation. In the high dose group, a high incidence of hair loss was observed in both genders. A decrease in the level of food consumption, followed by a decrease in body weight gain was also observed in both genders. At the scheduled necropsy, the gross postmortem examinations revealed an increase in the incidence of thymic atrophy, paleness of the thoracic and abdominal organs in both genders and an increase in the serum testosterone concentration. In addition, there was a decrease in the thymus weight of the males and an increase in the liver, spleen, kidneys, lung, and heart weights of the females. There was an increase in the number of fetal deaths and post-implantation losses as well as a decrease in the litter size found at the caesarean section of the dams. No treatment-related effect on the histopathological findings, sexual cycle, pre-coital time, mating index, fertility index, pregnancy index, and sperm parameters was observed. There were no adverse effects on the general findings and reproductive performance of the parent animals and early embryonic development in the low and medium dose groups. Overall, the no-observed-adverse-effect levels (NOAELs) of CKD-602 are believed to be 14 microg/kg for both general toxicity and early embryonic development, and more than 42 microg/kg for the reproductive performance of the parent animals.     

Chronic toxicity of microencapsulated bromodichloromethane administered in the diet to Wistar rats.

A chronic feeding study was carried out in Wistar rats using microencapsulated bromodichloromethane. The test substance was administered in the diet at doses of 0, 0.014, 0.055 and 0.22% for 24 months. Rats were sacrificed after 6, 12, 18 and 24 months of continuous dosing. The results showed a suppression of body weight gain in the 0.22% group for both males and females. Dose related changes were clearly observed in the liver with histopathological findings including fatty degeneration in the 0.014% or higher dose male groups, and fatty degeneration and granuloma in the 0.055 and 0.22% group females, as well as bile duct proliferation and cholangiofibrosis in the 0.22% group for both males and females. No significant differences in incidences or numbers of neoplastic changes were seen between control and any of the treatment groups. There were no dose-related non-neoplastic lesions in the kidneys of either sex. Lowest-observed-adverse-effect-level was determined to be 6.1 mg/kg/day under the present experimental conditions.     

一类新药尖吻蝮蛇凝血酶对SD大鼠生育力和早期胚胎发育的影响

目的观察尖吻蝮蛇凝血酶对SD大鼠生育力与早期胚胎发育的影响,为临床用药提供依据。方法对雌雄动物由交配前到交配期直至胚胎着床,经静脉注射给予不同剂量尖吻蝮蛇凝血酶(0.1、0.2、0.4 U·kg~(-1))。结果尖吻蝮蛇凝血酶对雌性、雄性SD大鼠生育力与早期胚胎发育无明显毒性和干扰作用。结论尖吻蝮蛇凝血酶SD大鼠生育力与早期胚胎发育毒性试验的安全剂量为0.4 U·kg~(-1)。     

Male fertility study on N,N-dimethylacetamide administered by the inhalation route to Sprague-Dawley rats

Male Sprague-Dawley rats were exposed to N,N-dimethylacetamide (DMAC) and mated to untreated virgin females. Mean analytical exposure concentrations were 40, 116, and 386 ppm, respectively. A control group was exposed to air containing no DMAC. A total of 69 d of exposure to DMAC at these levels produced treatment-related effects of increased liver weights and liver/body weight ratios in the high- and medium-exposure groups of male rats. Reproductive data indicated no treatment-related effects on copulation efficiency or efficiency in effecting pregnancy, and there were no detectable treatment-related effects on preimplantation loss, postimplantation loss, embryotoxicity, or fetotoxicity in litters of females mated to males exposed to DMAC at the levels used in this study. The significance of these findings is discussed.     

坤灵丸对雌性大鼠生育力及胚胎-胎仔发育影响的研究

目的 评价坤灵丸对雌性大鼠的生育力及胚胎发育的影响。方法 在生育力及早期胚胎发育毒性研究中,每组25只雌性SD大鼠从交配前14 d开始,每天ig给予1次坤灵丸（0.875、1.750、3.500 g制剂/kg）或去离子水至妊娠第7天,评价雌鼠症状、体质量、摄食量、生殖能力和早期胚胎发育情况;在胚胎-胎仔发育毒性研究中,每组25只雌性SD大鼠从妊娠第6~15天每天ig给予坤灵丸（0.875、1.750、3.500 g制剂/kg）或去离子水1次,评价妊娠母鼠的症状、体质量、摄食量、生殖能力及胎仔的体质量、性别和外观、内脏、骨胳发育的畸形或变异。结果 在生育力及早期胚胎发育毒性研究和胚胎-胎仔发育毒性研究中,坤灵丸给药剂量达到3.500 g/kg时未产生任何药物相关的母体毒性和胚胎毒性。结论 本试验条件下,雌鼠生育力及胚胎发育毒性的安全剂量为3.500 g/kg,按照体质量计算,该剂量相当于人用最大临床使用剂量的43.2倍。     

Subchronic toxicity study in rats and genotoxicity tests with polyvinyl alcohol.

The potential systemic and neurotoxicity of polyvinyl alcohol (PVA) was assessed when fed in the diet to male and female Sprague-Dawley rats for 90 days at doses of 2000, 3500 and 5000 mg/kg/day. Control rats received untreated standard laboratory diet. Assessments included clinical observations, ophthalmology, body weight and food consumption, hematology, coagulation, clinical chemistry, urinalyses, motor activity and functional observational battery evaluations and gross and microscopic pathology. The only test-article-related finding observed during the study was unformed stool with brown/black anogenital staining in rats fed 3500 and 5000 mg/kg/day. This finding was attributed to the high levels of test article being consumed and subsequently excreted in the stool. It was not accompanied by macroscopic or microscopic changes in these rats. No test-article-related changes were seen in mortality, ophthalmology, body weight and food consumption data, hematology, clinical chemistry, urinalysis data, functional observational assessments, motor activity, organ weight data and macroscopic and microscopic examinations. Doses of 2000, 3500 and 5000 mg/kg/day of PVA administered as a dietary admixture to male and female Sprague-Dawley rats for up to 90 days did not result in any adverse, toxicological effects. The no-observed-adverse-effect level (NOAEL) was determined to be 5000 mg/kg/day. PVA showed no evidence of mutagenic activity in the Ames test, mouse lymphoma assay and the mouse micronucleus test. (A critical evaluation of the available information on PVA will appear in a review to be published in Food and Chemical Toxicology 2003, 41, 319-326)     

Toxicities of microencapsulated tribromomethane, dibromochloromethane and bromodichloromethane administered in the diet to Wistar rats for one month.

The gelatin-starch syrup microencapsulation method was applied to subacute toxicity studies of tribromomethane (TBM), dibromochloromethane (DBCM) and bromodichloromethane (BDCM). Groups of Wistar rats (7 males and 7 females) both sexes were given diet containing microcapsules of each of these trihalomethanes (THMs) at the following concentrations: TBM, 0.068, 0.204 and 0.612% in males, and 0.072, 0.217 and 0.651% in females; DBCM, 0.020, 0.062 and 0.185% in males, and 0.038, 0.113 and 0.338% in females; BDCM, 0.024, 0.072 and 0.215% in males, and 0.024, 0.076 and 0.227% in females. Suppression of body weight gain was seen in each high-dose males fed TBM or BDCM and females fed DBCM or BDCM. Histopathologically, hepatic lesions such as vacuolization and swelling of liver cells were significantly noted in both sexes of all groups fed TBM, in both sexes of the middle- and high-dose groups fed DBCM, and in males of the high-dose group and in females of the middle- and high-dose groups fed BDCM. In addition, single cell necroses were observed in males and females fed DBCM and in males fed BDCM. Hepatic cord abnormalities were also noted in males of the high-dose group fed BDCM. Although no increases in serum transaminase activities (ASAT, ALAT) were evident in either sex fed any of the THMs, decreases in triglyceride content, cholinesterase and lactate dehydrogenase activity were observed. Renal lesions reported to occur in gavage studies were not found in the present feeding study. Lowest-observed-adverse-effect-level (LOAEL) of TBM and no-observed-adverse-effect-level (NOAEL) of DBCM and BDCM were determined to be 56.4 mg/kg, 18.3 mg/kg and 20.6 mg/kg, respectively, under the present experimental conditions.     

银杏内酯B注射液对大鼠生育力及早期胚胎发育毒性研究

目的 观察银杏内酯B （GGB）注射液对SD大鼠生育力及早期胚胎发育毒性。方法 SD大鼠随机分为GGB注射液低、中、高剂量（30、60、120 mg/kg,分别相当于临床等效剂量的52、105、210倍）组及溶媒对照组（生理盐水）,每组雌雄各25只。每天尾静脉推注给药1次,雄鼠连续给药4周,雌鼠连续给药2周,以1：1合笼交配,雄鼠继续给药至交配成功,雌鼠继续给药至妊娠第7天。在确定雌鼠受精后处死同笼的雄鼠,解剖检查睾丸和附睾等生殖器官及精子的数量、活力和形态。雌鼠妊娠第14天处死,解剖检查卵巢、子宫和胚胎的情况。结果 雄性大鼠GGB注射液高剂量组给药2.5、3.0、3.5、4.0周体质量与溶媒对照组比较显著增高（P<0.05）,雄性大鼠给药第2周中、高剂量组摄食量与溶媒对照组比较显著增高（P<0.05、0.01）,给药第3周高剂量组摄食量与溶媒对照组比较亦显著增高（P<0.01）,摄食量的增高与体质量的显著性增长呈现出较好的一致性,说明供试品对体质量的影响跟饲料的摄入有关。GGB注射液对雄性大鼠的睾丸、附睾的质量及脏器系数、精子数量、精子活力、精子形态没有显著影响;对雌鼠的体质量、摄食、孕鼠的黄体、活胎、死胎、吸收胎、着床数、交配率、受孕率、着床前丢失率和着床后丢失率没有显著影响。结论 在本试验条件下,未见GGB注射液对大鼠的生育力及早期胚胎的发育有毒性作用。     

Effects of oral,subchronic cadmium administration on fertility,prenatal and postnatal progeny development in rats

Cadmium chloride was administered by gavage to female rats 5 days a week for 5 weeks, then during mating and gestation periods at doses of 0.04, 0.4, and 4 mg Cd/kg/day. Treatment with cadmium neither affected the survival and fertility of females, nor produced overt fetotoxic effects. Fetal cadmium concentration was not related to the level of exposure. Litter size, body weight gain and viability of offspring during 2 months after parturition were similar in all groups. The exploratory locomotor activity of 2-month-old males and females born to rats given 0.4 and 4 mg Cd/kg/day was significantly reduced. The progeny of cadmium-treated females showed decreased performance in the rotarod test. In general, the degree of behavioral impairment was dose-related.     

Vaginal absorption of polyvinyl alcohol in Fischer 344 rats

Polyvinyl alcohol (PVA) is a polymer with a wide range of molecular weights and uses. Recently, low molecular weight formulations of PVA have been used as components of contraceptive products designed for intravaginal administration in human females. Previous studies in animals have determined that little or no absorption of PVA occurs from the gastrointestinal (GI) tract. However, there is some concern that PVA of lower molecular weights might be absorbed across membranes of the reproductive tract. Consequently, this work has investigated the absorption of low molecular weight PVA across biological membranes of the reproductive and GI tracts of Fischer 344 rats. Oral administration of ten consecutive daily doses of 14C PVA resulted in little apparent absorption of the dose from the GI tract. In contrast, intravaginal administration of 14C PVA resulted in increasing concentrations of PVA-derived radioactivity in major tissues following one, three or ten daily doses of the estimated human dose of 3 mg/kg. PVA-derived radioactivity was concentrated mainly in the liver, reaching a peak greater than 1750 ng equivalents/g tissue 24 hours following ten daily doses. Over 300 ng equivalents/g tissue were still present in the liver 30 days following the last dose.     

Effects of cobalt sulfate on prenatal development of mice, rats, and rabbits, and on early postnatal development of rats

The effects of cobalt sulfate administered to pregnant C57BI mice, OFA-SD rats, and New Zealand rabbits was studied on fetal and postnatal offspring. Cobalt concentration in the maternal blood was increased in proportion to the administered doses. Cobalt crossed the placenta and appeared in the fetal blood and amniotic fluid. Regardless of the administered dose of cobalt sulfate, cobalt concentration in the blood peaked 2 h after administration. Cobalt produced dose-dependent maternal toxicity and was found to be embryotoxic in all three species, as evidenced by elevated frequency of fetuses with body weight or skeletal retardation and embryolethality. Cobalt increased the frequency of major anomalies significantly in mice and rats, with anomalies of the eyes, kidneys, skull, spine, and sternum in mice, and anomalies of the urogenital system in rats. Cobalt sulfate was not teratogenic in rabbits. Intra-amnial administration of cobalt sulfate produced a dose-dependent increase of the frequency of dead fetuses, and weight retardation of the live fetuses. The direct cytotoxic effect probably plays a role in the embryotoxic and teratogenic effects of cobalt. The postnatal examinations revealed a decrease of the perinatal index in the treated group. The body weight of the pups in the treated group was lower during wk 1 of life, but no difference was found between the control and treated by the end of wk 2. Eye opening was completed in the usual time period in both groups, while time of appearance of the teeth, descending of the testes, shaping of ears, and development of hearing was delayed in the treated group. The development of muscle strength and of the locomotor system was delayed. All the functions studied (forward movement, swimming, righting reflex) normalized by postnatal d 21, with the exception of muscle strength. It was concluded that cobalt sulfate exposure decreases the perinatal viability of the fetuses, but the functions of the surviving fetuses with perinatal retardation become compensated by postnatal wk 2-3. The development of fetuses is undisturbed thereafter.     

Investigation of carcinogenicity for levamisole administered in the diet to F344 rats

A two year carcinogenicity study of anthelmintic drug levamisole (LV) was performed using 50 male and 50 female F344 rats at dietary drug concentrations of 0, 60, or 300 ppm. The daily intakes of LV were calculated to be 2.6, 12.9 mg/kg b.w./day for males and 2.9, 14.1 mg/kg b.w./day for females, respectively. No significant differences in general condition and survival rate (82%, 74%, 80% in males and 84%, 84%, 84% in females, respectively) were observed. In the 300 ppm group, suppression of body weight gain was observed from the onset of treatment and reduction in final body weights was 6% in males and 11% in females. Significant increases in the absolute and/or relative weights of the lungs, heart, spleen, liver, kidneys, and adrenals were observed in males and/or females treated with 300 ppm. Some of high incidences neoplasms were observed, and there were also tendencies to increase for mammary gland fibroma and thoracic/abdominal cavity mesothelioma in males. However, there were no significant inter-group differences in incidences, histopathological types or differences compared with historical control data. Thus, it was concluded that LV was not carcinogenic to male and female F344 rats under the experimental conditions.     

Decreased fertility in male rats administered the 5 alpha-reductase inhibitor, finasteride, is due to deficits in copulatory plug formation.

Oral administration of 80 mg/kg/day of finasteride, a potent specific inhibitor of 5 alpha-reductase, to sexually mature male Sprague-Dawley rats for 24 to 38 weeks caused an approximate 30% to 40% decrease in fertility. There were no effects on mating indices or implants per pregnant female. From the mating trials, a selected group of treated males with poor reproductive performance was compared to a selected group of control males with good reproductive performance. Observed matings showed no qualitative effects on mating behavior or ejaculation. However, finasteride-treated males did not form or formed small and improperly positioned copulatory plugs, which are required in rats to transport sperm into the uterus. Intrauterine insemination of epididymal sperm from males that were nonfertile by natural mating resulted in similar numbers of embryos and unfertilized oocytes recovered from controls and finasteride-treated males, confirming that there was no effect of finasteride on the ability of sperm to fertilize. Decreased fertility of finasteride-treated males was due to failure to form copulatory plugs and is related to decreased weight of seminal vesicles and prostate, an expected pharmacologic effect. Testes weight was unaffected. Decreased fertility in male rats after finasteride administration is considered a species specific effect. The mechanism of the decrease in rats is not likely to be relevant to species that do not form copulatory plugs.     

Perinatal toxicology of mirex administered in the diet: I. viability,growth, cataractogenicity and tissue levels

Mirex was administered at a concentration of 25 ppm in the diet to pregnant rats. Animals were allowed to give birth and the pups were cross-fostered. Prenatal exposure to mirex resulted in decreased postnatal viability. Growth was decreased in litters exposed postnatally. Postnatal exposure to the pesticide also resulted in a high incidence of cataracts and/or outlined lenses. Mirex crossed the placenta and significant quantities of the chemical were found in newborns. Following postnatal administration of mirex, tissue levels were found to rise through day 21 (weaning) and thereafter to slowly decline. Tissue levels (ppm) were generally found to be in the order of fat > liver > kidney > brain > eyes.     

Effects of alcohol consumption and accompanying diet on metabolic response to arginine in chronic alcoholics.

OBJECTIVE: To evaluate, in chronic alcoholics, the effects of accompanying diet on the release of insulin (IRI) and glucagon (IRG) and on the hepatic glucose production. METHOD: We evaluated variations of the response to the infusion of arginine into 16 male and 8 female chronic alcoholics divided into three groups of eight subjects each before and after three weeks of treatment with: (1) an isocaloric diet plus 200 g/day of ethanol; (2) an hypocaloric diet without alcohol (17.5 kcal/kg/day); and (3) an isocaloric diet (35 kcal/kg/day). Statistical evaluation was done by Kruskall-Wallis ANOVA and by Wilcoxon matched-pairs signed rank test. RESULTS: After isocaloric diet plus ethanol both IRI/IRG ratios and plasma glucose during arginine testing remained unmodified; after the hypocaloric diet IRI/IRG remained unmodified and the arginine-induced plasma glucose rise was slightly but significantly reduced; after the isocaloric diet there was a strong decrease of the arginine-induced plasma glucose rise because of a significant increase in the insulin/glucagon ratio. CONCLUSIONS: In chronic alcoholics the replacement of the usual hypocaloric diet with an isocaloric one while maintaining alcohol consumption does not modify the metabolic response to arginine administration; the hypocaloric diet without alcohol increases insulin and glucagon release and slightly decreases liver glycogenolysis; the replacement of the usual hypocaloric diet with an isocaloric one together with alcohol withdrawal stimulates insulin, inhibits glucagon release and lowers glycogenolysis much more than observed with hypocaloric diet alone.     

Effects of 2-methoxyethanol on fetal development, postnatal behavior, and embryonic intracellular pH of rats

The industrial solvent 2-methoxyethanol (2ME) is a reproductive and developmental toxicant when administered by inhalation, gavage, and IP injection. The present research established that this solvent can produce teratogenicity in rats when administered in liquid diet. Groups of 10 Sprague-Dawley rats were given various percentages of 2ME in liquid diet on gestation days 7-18. Day 20 fetuses were examined for visceral or skeletal malformations. Concentrations above 0.025% 2ME (approximately 73 mg/kg/day) produced total embryo-mortality. Cardiovascular malformations were produced at lower levels. The teratogenic no-effect level was 0.006% 2ME (16 mg/kg). In a second experiment, groups of 12 Sprague-Dawley rats were given 0, 0.006 and 0.012% of 2ME as above. Litters were culled to 8 pups, and tested for auditory and tactile startle and conditioned lick suppression, and for performance in figure-8 activity and the Cincinnati water maze on postnatal days 48-65. The high dose of 2ME produced approximately 50% mortality in the offspring and increased the number of errors in the Cincinnati maze. No other behavioral effects were observed at either dose. An interaction study was conducted to determine if simultaneous exposure to 2ME and ethanol would reduce the teratogenicity of 2ME, but no reduction was observed. The hypothesis that 2ME acts by altering embryonic intracellular pH was tested by injecting 0.33 ml/kg of 2ME into rats on gestation day 13, and determining embryonic intracellular pH at 2, 4, 8, and 24 hours thereafter. There was an increase in pH at 4 hours, but not at later time points. Another group of rats was given 2ME along with amiloride, which blocks the sodium/hydrogen antiporter. The combined 2ME-amiloride exposure produced an incidence of cardiovascular malformations in fetuses twice that of 2ME alone. These studies confirmed the structural teratogenicity of 2ME even when given in liquid diet, as it was given for the first time in the present study. At nonteratogenic doses, developmental toxicity (e.g., postnatal deaths) persisted, but only limited evidence of behavioral teratogenicity was observed. The pH data are consistent with the concept that 2ME may alter embryonic intracellular pH at critical stages of organogenesis.     

Effects of heat treatment on the permeability of polyvinyl alcohol films to a hydrophilic solute

Polyvinyl alcohol (PVA) films may be useful as release-controlling membrane systems. Untreated, they are readily permeable to water and hydrophilic drugs. Because heating has been used to increase crystallinity and thus reduce the solubility and swelling in water of PVA films, we have studied the effects of heat on the permeability of PVA films to a water-soluble drug marker. Heat treatment was varied in the temperature range 100-200 degrees C for 1 h. The effect of time of heating was studied at 100 degrees C for 0.5-160 h. After pre-equilibration with water (heat-treated membranes remained intact, untreated ones dissolved), membrane permeabilities to methylene blue in aqueous solution (37 degrees C) were determined in a rotating diffusion cell. Permeabilities decreased with increased heating times (0.98-0.039 cm X min-1 for 0.5-160 h at 100 degrees C, respectively). Heating in air or N2 produced similar results. Further dramatic decreases in permeability occurred with increasing pretreatment temperatures; membrane permeability fell by a factor of approximately 500 with increasing temperature in the range 100-200 degrees C. There was no evidence of decomposition at temperatures less than or equal to 190 degrees C for 1 h. Results were consistent with literature reports of heat-induced increases in crystallinity. Membranes were simple to prepare and permeability could be controlled without recourse to chemical manipulation.     

An assessment of neurotoxicity of aroclors 1016, 1242, 1254, and 1260 administered in diet to Sprague-Dawley rats for one year.

As part of a comparative chronic toxicity/oncogenicity study of different Aroclors (1016, 1242, 1254, and 1260), neurotoxicity was assessed in male and female Sprague-Dawley rats using functional observational battery (FOB) and motor activity tests, and histopathologic evaluation of selected nervous system tissues. Doses varied by Aroclor and ranged from 25 to 200 ppm in the diet. Animals were evaluated prior to initiation of dosing and at 13, 26, 39, and 52 weeks of exposure. Clinical signs, body weights, and feed consumption were evaluated weekly. Data analysis of FOB and motor activity results revealed several instances where Aroclor-treated groups were different from control. However, these were considered incidental, as they lacked any consistent dose- or time-related pattern that would suggest Aroclor-induced neurotoxicity. The nonremarkable findings during each of the four assessments were supported by the absence of any treatment-related clinical signs or mortality. Decreased body weight gain was evident in the male 100 ppm Aroclor 1254 dose group and in all female Aroclor 1254 dose groups late in the study (when a linear relationship was assumed between body weight and time), correlating with decreased feed consumption. Although a variety of incidental, spontaneous, degenerative changes were found in nervous tissue evaluated histopathologically, these changes were seen with similar incidence and severity in treated and control groups. No lesions were found that could be attributed to Aroclor-related neurotoxicity. In summary, 52 weeks of exposure to Aroclors 1016, 1242, 1254, or 1260 mixed in the diet did not yield any functional or morphologic changes indicative of PCB-induced neurotoxicity.