Long-term in vivo carcinogenicity study of nalidixic acid in CDF1 mice

Nalidixic acid (NA), a drug used for the treatment of urinary-tract infections, was administered in the diet to groups of 51 male and 51 female CDF1 mice at concentrations of 0, 0.08 and 0.16% for 76 wk. All the surviving animals were killed at wk 85 after 9 wk on the basal diet. Survival of the treated male and female mice was similar to that of the corresponding controls. The body weights were slightly lower in high- and low-dose males and in high-dose females than in the controls. All groups showed relatively high incidences of tumours of the small intestine, lung and haematopoietic organs in both sexes, of the liver and Harderian gland in males and of the uterus in females. However, there were no statistically significant differences between NA-treated and control mice of either sex in the incidences of tumours in any organs. It was therefore concluded that, under the conditions of this study, NA showed no carcinogenic potential in either male or female CDF1 mice.     

Carcinogenicity and toxicity study of m-phenylenediamine administered in the drinking-water to (C57BL/6 × C3H/He)F1 mice

m-Phenylenediamine (m-PDA, CAS: 108-45-2), a component of hair-dye formulations, was administered in the drinking-water to groups of female and male (C57BL/6 x C3H/He)F1 (B6C3F1) mice at concentrations of 0.02 or 0.04% for 78 wk. All the surviving mice were killed after a further 5-7 wk on untreated drinking-water, 83-85 wk after the start of treatment. Survival of the treated mice was similar to that of the corresponding controls. Body weights were significantly lower in high-dose females and males and somewhat lower in low-dose females than in the controls. The incidences of hepatocellular tumours were low to moderate in all male groups and in the control females, but the treated groups had significantly lower incidences than the controls. A few tumours of the lungs, haematopoietic organs and other organs and tissues were observed in all female and male groups. However, there were no statistically significant increases in the incidences of tumours in these organs and tissues in m-PDA-treated mice of either sex. Under the conditions of this study m-PDA showed no carcinogenic potential in either female or male B6C3F1 mice when administered in drinking-water. No non-neoplastic changes attributable to the compound were found in the treated mice, except for the deposition of brown pigment in follicular epithelial cells of the thyroid gland and in macrophages in some organs and tissues, and pigment impregnation of the bronchioli.     

Chronic inhalation toxicity and carcinogenicity study of propylene oxide in Wistar rats

Four groups of 100 Wistar rats of each sex were exposed by inhalation to 0, 30, 100 or 300 ppm propylene oxide for 6 hr/day, 5 days/wk for 28 months. After 12, 18 and 24 months ten rats/sex/group were killed to provide interim haematological, biochemical and urinary data. Mortality was increased by wk 115 in both sexes in the 300-ppm group and by wk 119 in females of the 100-ppm group. Body weights were lower than those of the controls throughout the study in males of the 300-ppm group and in females of the 300-ppm group during the first year of the study. Increased incidences of degenerative and hyperplastic changes of the nasal mucosa were observed in all exposed groups. Exposure to 300 ppm propylene oxide was associated with an increased incidence of both benign and malignant mammary tumours in females. There was no increase in the incidence of any particular type of tumour other than mammary tumours. The total number of rats bearing malignant tumours at sites other than the mammary glands was increased in both sexes in the 300-ppm group compared with the controls.     

Carcinogenicity study of ammonia-process caramel in F344 rats

The carcinogenicity of ammonia-process caramel, a food colouring, was examined in F344 rats. Caramel was dissolved in distilled water at levels of 0, 1 and 4% and groups of 50 male and 50 female rats were given 20-25 ml of one of these solutions/rat/day as their drinking water for 2 yr. There were no significant differences between the total incidences of tumours or mean survival times of control and experimental groups. A variety of tumours developed in all groups including the control group, and no dose-related effects were found either in the incidence or induction time of tumours in the various organs and tissues except in the pituitary gland of males, in which the incidence of tumours in males given 4% caramel solution was significantly higher than that in controls. Pituitary tumours are among the most common spontaneous tumours in ageing rats of this strain and have a variable incidence. In addition, almost all pituitary tumours detected in males given the 4% solution were microscopic tumours, and there was no significant difference between controls and treated groups in the incidence of hyperplasia or pre-neoplastic lesions in the pituitary gland. These results indicate that the significantly higher incidence of pituitary tumours in males given the 4% caramel solution was not related to caramel administration, but could be explained by the variability of the incidence of spontaneous pituitary tumours. Thus it is concluded that under these experimental conditions ammonia-process caramel was not carcinogenic in F344 rats.     

Lack of carcinogenicity of phenytoin in (C57BL/6 x C3H)F1 mice

Groups of 50 B6C3F1 mice of each sex were given 0.012% or 0.006% phenytoin in their powdered diet for 78 wk and were then fed a basal diet for 8 wk. Control groups of 50 mice of each sex were fed powdered basal diet for 86 wk. Mean total intakes of phenytoin per mouse were 301 and 150 mg in males, and 292 and 154 mg in females, respectively. The survival rates of each group at week 86 were 72-86% in males, and 86-94% in females. Liver-cell tumors, alveolar tumors, and Harderian-gland adenomas in male mice, malignant lymphomas and/or leukemias in female mice, and a few tumors in other organs of both sexes were found. The total number of hepatocellular tumors in mice treated with the high dose of phenytoin was significantly smaller than that of control mice in males (p less than 0.05). However, hepatocellular carcinomas developed 15 to 3 wk earlier in a few mice of phenytoin-treated males than in the controls. In other organs, no significant increase of any particular tumor type was observed in the treated groups of both sexes. Thus, phenytoin was not carcinogenic in B6C3F1 mice in this study.     

Triprolidine: 104-Week Feeding Study in Rats

The antihistamine, triprolidine hydrochloride, was fed at dietaryconcentrations of 0, 250, 1000, or 2000 ppm (as the free base)to groups of 60 Fischer 344 (F344) rats of each sex for up to2 years to evaluate its potential carcinogenicity. Up to 12per sex from each group were killed at 65 weeks, and hematology,clinical chemistry, and histopathology were evaluated. A completehistopatho-logical evaluation was performed on all other animals;survivors were killed at 2 years. Survival was significantlyextended in tri-prolidine-treated males and females, particularlyat the high dose. At the close of the study high-dose malesand females had gained significantly less body weight than controls.Among rats killed at 65 weeks females in the mid- and high-dosegroups weighed significantly less than controls, but weightsof control and dosed males were not significantly different.The incidences of numerous lesions tended to decrease with increasingtriprolidine dose. In females, clitoral gland adenomas, thyroidc-cell hyperplasia and neoplasia, mammary gland hyperplasiaand fibroadenomas, and uterine stromal polyps, and in males,anterior pituitary gland adenomas, preputial gland neoplasia,thyroid c-cell hyperplasia, pancreatic islet neoplasia, mononuclearcell leukemia, and the combination of lymphocytic, histiocytic,and undifferentiated cell malignant lymphomas and mononuclearleukemia, all exhibited negative dose trends. Cytoplasmic alterationsof the parotid gland and numerous liver lesions tended to bemore frequent in treated than in control animals. Liver lesionsthat exhibited positive dose trends include chronic inflammationand centrilobular fatty change in both sexes, mixed cell foci,and the combination of mixed cell foci and eosinophilic fociin females, and in males, basophilic foci and eosinophilic foci.Triprolidine was not carcinogenic in F344 rats.     

Chronic Toxicity and Carcinogenicity Studies of 1-Methylnaphthalene in B6C3F1 Mice

The carcinogenic potential of 1-methylnaphthalene (1-MN), acompound which exists widely in the environment, was investigatedin B6C3F1 mice. Groups of 50 male and 50 female mice were givendiets containing 0, 0.075, or 0.15% 1-MN for 81 weeks. Bothtreatment groups developed pulmonary alveolar proteinosis athigh incidence, with 46.0 and 34.7% of females and 46.0 and38.0% of males, respectively, being affected. Total lipid andphospholipid levels in sera and monocytes in peripheral bloodwere also significantly increased in 1-MN-treated female andmale mice in contrast with control values. The incidences ofbronchiolar/alveolar adenomas in the lungs of male mice givenboth 0.075 or 0.15% 1-MN were 26.0 and 24.0%, respectively,in both cases significantly increased in contrast with the 4.1%observed for control males. However, neither dose dependencenor significant difference in the incidences of bronchiolar/alveolarcarcinomas between 1-MN-treated and control male mice was observed.The incidences of other tumors also were similar in both 1-MN-treatedand control groups. The results of the present experiment thussuggested a possible weak carcinogenic potential of 1-MN tothe lung of male but not female B6C3F1 mice.     

Non-carcinogenicity of Capsaicinoids in B6C3F1 Mice

The carcinogenicity of a mixture of capsaicinoids (64.5% capsaicin and 32.6% dihydrocapsaicin) was examined in B6C3F₁ mice. In a 13-week toxicity study, renal toxicity was observed in 1% capsaicinoid-treated males. Next, groups of 50 mice of each sex were given 0, 0.025, 0.083 or 0.25% capsaicinoids in powdered diet for 79 weeks and killed in week 83. Food intake was reduced in mice of all capsaicinoid-treated groups, especially females, because of the pungency of capsaicinoids, and inhibition of body weight gain was apparent in females. The numbers of tumour-bearing females in the high-dose groups were significantly lower than that in the controls, and the incidences of hepatocellular neoplasms in both sexes were negatively correlated with the dose of capsaicinoids (Cochran–Armitage trend test). Renal cell adenomas developed in one mouse each of 0.025 and 0.25% capsaicinoid-treated males. The incidences of other tumours were similar in the treated and control groups. Thus, the present study indicated that a mixture of capsaicinoids is not carcinogenic in B6C3F₁ mice.     

Acrylonitrile is a multisite carcinogen in male and female B6C3F1 mice.

Acrylonitrile is a heavily produced unsaturated nitrile, which is used in the production of synthetic fibers, plastics, resins, and rubber. Acrylonitrile is a multisite carcinogen in rats after exposure via gavage, drinking water, or inhalation. No carcinogenicity studies of acrylonitrile in a second animal species were available. The current studies were designed to assess the carcinogenicity of acrylonitrile in B6C3F1 mice of both sexes. Acrylonitrile was administered by gavage at 0, 2.5, 10, or 20 mg/kg/day, 5 days per week, for 2 years. Urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine were measured as markers of exposure to acrylonitrile. In general, there were dose-related increases in urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine concentrations in all dosed groups of mice and at all time points. Survival was significantly (p < 0.001) reduced in the top dose (20 mg/kg) group of male and female mice relative to controls. The incidence of forestomach papillomas and carcinomas was increased in mice of both sexes in association with an increase in forestomach epithelial hyperplasia. The incidence of Harderian gland adenomas and carcinomas was also markedly increased in the acrylonitrile-dosed groups. In female mice, the incidence of benign or malignant granulosa cell tumors (combined) in the ovary in the 10 mg/kg dose group was greater than that in the vehicle control group, but because of a lack of dose response, this was considered an equivocal finding. In addition, the incidences of atrophy and cysts in the ovary of the 10 and 20 mg/kg dose groups were significantly increased. The incidences of alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in female mice treated with acrylonitrile at 10 mg/kg/day for 2 years. This was also considered an equivocal result. In conclusion, these studies demonstrated that acrylonitrile causes multiple carcinogenic effects after gavage administration to male and female B6C3F1 mice for 2 years.     

Carcinogenicity study of sodium hypochlorite in F344 rats

The carcinogenic potential of sodium hypochlorite was examined in F344 rats. Groups of 50 males or 50 females were given sodium hypochlorite in their drinking-water, at concentrations of 0.1 and 0.05% for males and 0.2 and 0.1% for females, for 104 wk. Similar numbers of male and female rats received distilled water without supplement throughout the experiment. All surviving rats were killed at wk 112 (after 8 wk on untreated tap-water). Rats of both sexes given the chemical showed a reduction in body-weight gain, but haematological and biochemical examination of the blood showed no changes due to treatment, and no significant lesions attributable to the treatment were detected in any tissue in the histopathological investigation. Although a variety of tumours developed in all groups, no dose-related change in either the incidence or latent period of tumours was observed for any organ or tissue in either sex. Under the experimental conditions described, therefore, sodium hypochlorite was not carcinogenic in F344 rats.     

Inhalation carcinogenicity of 1,1,1-trichloroethane in rats and mice

Abstract

Carcinogenicity of 1,1,1-trichloroethane (TCE) was examined by an inhalation exposure of F344 rats and BDF1 mice of both sexes to TCE at 0, 200, 800 or 3200?ppm for 6?h/d, 5?d/week for 104 weeks. In male rats, the incidences of bronchiolo-alveolar adenomas and peritoneal mesotheliomas were significantly increased in the 800 and 3200?ppm-exposed groups, respectively. The incidence of bronchiolo-alveolar adenomas in the 3200?ppm-exposed groups exceeded the range of historical control data in the Japan Bioassay Research Center. In female rats, the tumor incidences were not increased in any organs of the TCE-exposed groups. In male mice, a significant positive trend with dose was shown for incidences of bronchiolo-alveolar carcinomas, combined incidences of bronchiolo-alveolar adenomas/carcinomas and hepatocellular adenomas. The incidence of Harderian gland adenomas was significantly increased in the 3200?ppm-exposed group, and malignant lymphomas of spleen at this highest dose exceeded the range of historical control data. In female mice, the combined incidence of bronchiolo-alveolar adenomas/carcinomas was significantly increased in the 3200?ppm-exposed group, and the incidences of hepatocellular adenomas and combined incidences of hepatocellular adenomas/carcinomas were significantly increased in the 200, 800 and 3200?ppm-exposed groups with dose dependence except the combined incidence of hepatocellular adenomas/carcinomas in the 200?ppm-exposed group. The incidences of bronchiolo-alveolar adenomas in the 3200?ppm-exposed group and combined incidences of hepatocellular adenomas/carcinomas in the 200?ppm-exposed groups exceeded the ranges of historical control data. Thus, this study provided clear evidence of inhalation carcinogenicity for TCE in both rats and mice.     

Carcinogenicity study on butylated hydroxytoluene (BHT) in Wistar rats exposed in utero

Groups of 60, 40, 40 and 60 F0 Wistar rats of each sex were fed a semi-synthetic diet containing butylated hydroxytoluene (BHT) in concentrations to provide intakes of 0, 25, 100 or 500 mg/kg body weight/day, respectively. The F0 rats were mated and groups of 100, 80, 80 or 100 F1 rats of each sex were formed from 40, 29, 30 and 44 litters, respectively. After weaning, the highest dose (500 mg BHT/kg/day) was lowered to 250 mg/kg/day for the F1 rats. The numbers of litters of ten or more pups at birth decreased with increasing BHT dose. At weaning, treated F1 rats had lower body weights than the controls, the extent of the reduction being dose related; the effect, which persisted throughout the study, was most pronounced in the males. The survival of BHT-treated F1 rats of both sexes was significantly better than that of the controls. No significant changes attributable to BHT treatment were found in the haematological parameters. F1 females on the highest dose showed an increase in serum cholesterol and phospholipids, and serum triglycerides were reduced in this group in both sexes. Dose-related increases in the numbers of hepatocellular adenomas and carcinomas were statistically significant (at P less than 0.05 or lower) in male F1 rats when all groups together were tested for heterogeneity or analysis for trend. The increase in hepatocellular adenomas and carcinomas in treated female F1 rats was only statistically significant for adenomas (at P less than 0.05) in the analysis for trend. All hepatocellular tumours were detected when the F1 rats were more than 2 yr old. Tumours were found in many other organs of some of the treated rats, but their incidence was not significantly different from that in controls. The role of BHT in the development of hepatocellular tumours requires further elucidation.     

Lack of carcinogenicity of enzymatically modified isoquercitrin in F344/DuCrj rats

The present study was conducted to evaluate the potential carcinogenicity of enzymatically modified isoquercitrin, administered in the diet at doses of 0.5% or 1.5% to groups of 50 male and female F344/DuCrj rats. Control males and females (50 rats each) were maintained on basal diet. Animals were observed for 104 weeks. There were no treatment-related clinical signs of toxicity in the treated groups. Body weights, feed consumption, survival rates and hematological findings for exposed rats of both sexes showed no variations among the groups. There was a slight but significant dose-dependent decrease in relative spleen weights in all treated groups, albeit with no histopathological variation. Overall histopathological evaluation of neoplasms and all tissues after 2 years showed that tumors developed in all groups including the controls. There was a non-significant tendency for increase in the incidence of pituitary gland adenomas in the high dose-treated females (45.5%) as compared to controls (27.7%), with a slight increase in hemorrhage incidences, but values for males were low and similar in both control and treated rats. There were no apparent effects of isoquercitrin on development of kidney neoplasms, hyperplasias or chronic nephropathy. Parathyroid adenomas or hyperplasias were found not affected by isoquercitrin treatment, and there were no differences in mammary gland fibroadenomas or hyperplasias between treated and control rats. Various tumors were found in other organs with no significant differences between the groups. In conclusion, under the conditions of this 2-year feeding experiment, no evidence was obtained of carcinogenicity of enzymatically modified isoquercitrin in male or female F344 rats.     

Carcinogenicity study in rats of phytic acid 'Daiichi', a natural food additive.

The carcinogenicity of phytic acid 'Daiichi' (PA), a natural food additive, was examined in Fischer 344 rats of both sexes. PA was added to the drinking-water of groups of 60 male and 60 female rats at levels of 1.25 or 2.5% for 100-108 wk. There was a dose-dependent reduction in the mean final body weights of rats treated with PA. Necrosis and calcification of the renal papillae were observed in PA-treated rats, but not in the controls. The incidences of necrosis (calcification) were as follows: one (three) out of 57 males given 2.5% PA; one (none) out of 59 males given 1.25% PA; 10 (17) out of 55 females given 2.5% PA; six (six) out of 58 females given 1.25% PA. Renal papillomas occurred in three of the high-dose male rats, four of the high-dose female rats, and three of the low-dose female rats. The development of papillomas seemed to be related to calcification and necrosis of the renal papillae induced by PA. While many other tumours developed in all groups, including the controls, the organ distribution of these neoplasms and their histological characteristics did not differ significantly from those known to occur spontaneously in this strain of rats.     

Long-term toxicity and carcinogenicity study of sodium o-phenylphenate in B6C3F1 mice

Sodium o-phenylphenate (OPP-Na) was given at dietary levels of O (control), 0.5, 1.0 and 2.0% to groups of 50 male and 50 female mice for 96 wk, and all the animals were maintained without OPP-Na for a further 8 wk. Both sexes given 2% OPP-Na and females given 0.5% and 1% OPP-Na showed growth retardation. Serum alkaline phosphatase activity in OPP-Na treated females was significantly increased in a dose-related manner. There were no treatment-related effects on clinical signs, mortality, urinalyses, haematology or organ weights. The incidences of several non-neoplastic and neoplastic lesions achieved statistical significance but none was considered to be related to treatment. There were increased incidences of haemangiosarcomas of the liver in males given 1% and of hepatocellular carcinomas in 1 and 2% males, and haemangiomas and leiomyomas of the uterus, present in the controls, were absent or decreased in all treated females. Therefore, this study did not demonstrate any clear carcinogenic effect of OPP-Na on mice at dietary levels of up to 2%.     

Carcinogenicity study of gamma-oryzanol in F344 rats.

The carcinogenic potential of gamma-oryzanol, a drug mainly used for the treatment of hyperlipidaemia, was studied in F344 rats. Groups of 50 males and 50 females were fed a diet containing 0 (control), 200, 600 or 2000 mg gamma-oryzanol/kg body weight/day for 2 yr. Although females in the highest dose group (2000 mg/kg body weight) showed a slight decrease in body weight at 104 wk, there were no treatment-related changes in general condition, food consumption, mortality, organ weight or haematology. Histopathological examination showed various tumours in all groups, including the control group. In the control and 2000-mg/kg groups, high tumour incidences were observed in the testes, pituitary and thyroid of males, and in the pituitary, uterus and mammary gland of females; however, there was no significant increase in the incidence of any tumours between the control and the 2000-mg/kg groups. The findings indicate that under the experimental conditions described gamma-oryzanol was not carcinogenic in F344 rats.     

Toxicity and carcinogenicity of nitrofurazone in F344/N rats and B6C3F1 mice

Toxicology and carcinogenesis studies were conducted by feeding diets containing nitrofurazone (99% pure) to groups of F344/N rats and B6C3F1 mice for 14 days, 13 wk or 2 yr. In the 14-day studies, in which doses ranged from 630 to 10,000 ppm, nitrofurazone was more toxic to mice than to rats. Accordingly, in the 13-wk studies, doses for rats ranged from 150 to 2500 ppm and for mice from 70 to 1250 ppm. At the higher doses, convulsive seizures and gonadal hypoplasia were observed in both species. Evidence of toxicity in rats also included degenerative arthropathy. For the 2-yr studies, rats were exposed to 0, 310 or 620 ppm nitrofurazone and the survival of male rats given 620 ppm was lower than that of controls (33/50, 30/50 and 20/50 in the control, 310- and 620-ppm groups, respectively). Nitrofurazone administration increased the incidences of mammary gland fibroadenomas in female rats (8/49, 36/50 and 36/50 in the control, 310- and 620-ppm groups, respectively). In male rats it was associated with a marginal increase in sebaceous gland adenomas and trichoepitheliomas of the skin, mesotheliomas of the tunica vaginalis, and tumours of the perputial gland. Nitrofurazone caused testicular degeneration (atrophy of germinal epithelium and aspermatogenesis) in rats, and degeneration of vertebral and knee articular cartilage in rats of both sexes. In mice, dietary concentrations of nitrofurazone for the 2-yr studies were 0, 150 or 310 ppm. In mice of each sex, nitrofurazone administration induced stimulus-sensitive convulsive seizures, primarily during the first year of study. In male mice, there was no evidence of any chemically-related carcinogenic effects, but there was a treatment-related decrease in survival (39/50, 31/50 and 27/50 in the control, 150- and 310-ppm groups, respectively). In female mice nitrofurazone induced ovarian lesions with increased incidences of benign mixed tumours (0/47, 17/50 and 20/50 in control, low- and high-dose groups, respectively) and granulosa cell tumours (1/47, 4/50 and 9/50 in control, low- and high-dose groups, respectively).     

Chronic Toxicity and Carcinogenicity Studies of 2-Methylnaphthalene in B6C3F1 Mice

The toxicity and carcinogenic potential of 2-methylnaphthalene(2-MN) were examined in B6C3F₁ mice. Groups of 50 male and 50female mice were given diets containing 0, 0.075, and 0.15%2-MN for 81 weeks. Both 0.075 and 0.15% 2-MN caused pulmonaryalveolar proteinosis at high incidence: 55.1 and 45.8% in femalesand 42.9 and 46.9% in males, respectively. The incidences oftotal lung tumors, including bronchiolar/alveolar adenomas andcarcinomas, were 20.4 and 12.2% in male mice given 0.075 and0.15% 2-MN, respectively, the former value being significantlyincreased compared with the 4.1% in control males. However,in the respective incidences of the adenomas and carcinomas,neither in-tergroup differences nor dose dependencies were observed.The incidences of other tumors did not differ between mice treatedwith 2-MN and the controls. The results indicated that 2-MNinduces pulmonary alveolar proteinosis but does not possessunequivocal carcinogenic potential in B6C3F₁ mice.     

Neoplastic and nonneoplastic lesions in aging osborne-mendel rats

Neoplastic and nonneoplastic lesions in 975 male and 970 female Osborne-Mendel rats used as controls in carcinogenesis tests were tabulated and evaluated. Three types of controls were considered—untreated controls (245 males, 245 females), controls administered corn oil in feed (530 males, 525 females), and controls administered corn oil by gavage (200 males, 200 females). Few neoplasms were seen in rats less than 18 months of age; the incidence of tumors markedly increased between 18 and 24 months of age. The incidence of some of the more common neoplasms, in which the combined incidence was greater than 1%, varied among the control groups, and in most cases the differences in incidences were not statistically significant. Hemangiosarcomas at all sites and C-cell adenomas of the thyroid in female rats were marginally significantly lower in controls given corn oil by gavage than in the other two groups. The occurrence of adenocarcinomas of the mammary gland was significantly higher in male controls given corn oil by gavage than in the other two groups. In untreated controls, the incidences of adrenal cortical adenomas in males and females and of pheochromocytomas in males were significantly higher than in both groups given corn oil. In rats administered corn oil in the feed, the incidences of pituitary adenomas in males and females, follicular cell adenomas of the thyroid in males, and endometrial stromal polyps in females were significantly higher than the incidences in the other two groups. The possible reasons for these differences are discussed. However, the types of tumors seen in the three control groups were morphologically comparable. The tumors observed included two types that had not previously been well characterized in Osborne-Mendel rats—malignant fibrous histiocytomas and lipomatous tumors of the kidney. Incidences of the more common nonneoplastic lesions are reported.     

Carcinogenicity study of a commercial sodium oleate in Fischer rats

Sodium oleate was added to the drinking-water of groups of 50 male and 50 female F344 rats at levels of 2.5 and 5.0% for 108 wk. The mean liver weight in males given 5% oleate was lower than that of the males given 2.5% oleate or distilled water alone. The mean thymus weight of females given 5% oleate was higher than that of females given 2.5% oleate or distilled water. There were no statistically significant differences between treated and control rats in the results of the urine and serum analyses or haematological determinations or in the incidence of tumours, apart from pancreatic tumours. The latter, in the males, showed some increase over the concurrent controls but did not differ significantly from the reported spontaneous incidence in this strain. It was concluded that sodium oleate does not induce tumours when given orally to F344 rats.