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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic (24-month) inhalation exposure to 5 or 10 ppm allyl glycidyl ether (AGE) induced nasal lesions in Osborne-Mendel rats and B6C3F1 mice. Inflammation, degeneration, regeneration, metaplasia, hyperplasia, and neoplasia were observed in the nasal mucosa. Squamous metaplasia and hyperplasia of the respiratory epithelium and degeneration and regeneration with subsequent squamous and/or respiratory metaplasia of the olfactory epithelium were observed in many AGE-exposed animals. Three primary nasal neoplasms (1 papillary adenoma, 1 squamous cell carcinoma, and 1 olfactory epithelial carcinoma) were observed in rats exposed to 10 ppm AGE, and 1 nasal papillary adenoma was observed in a rat exposed to 5 ppm. Four papillary adenomas and 2 hemangiomas were observed in the noses of mice exposed to 10 ppm AGE. Although the incidence of primary nasal tumors in AGE-exposed rats or mice was not statistically significant compared to the incidence in concurrent controls, the relative rarity of primary nasal tumors in historical controls and the concurrent presence of metaplastic and hyperplastic nasal lesions similar to those reported to be associated with induced tumors of nasal epithelia by other chemicals suggest that the nasal tumors observed may be related to AGE exposure. It was concluded that, in addition to lesions indicating a toxic effect on the nasal mucosa, inhalation exposure to AGE for 24 months resulted in some evidence of carcinogenicity of AGE for male mice, equivocal evidence of carcinogenicity for female mice and male rats, and no evidence of carcinogenicity for female rats.
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PMID:Morphology of nasal lesions induced in Osborne-Mendel rats and B6C3F1 mice by chronic inhalation of allyl glycidyl ether. 129 70

The carcinogenic activity of chloroform administered at 0, 200, 400, 900, and 1800 mg/liter in drinking water was studied in male Osborne-Mendel rats and female B6C3F1 mice. A second control group was included in the study and was restricted to the water consumption of the high-dose group. Animals were maintained on study for 104 weeks. Group sizes were adjusted at low doses such that a detectable tumor response would result at the lowest dose if there was a linear relationship with dose, and the higher doses produced responses similar to previous carcinogenesis bioassays of chloroform. The primary finding was that chloroform increased the yield of renal tubular adenomas and adenocarcinomas in male rats in a dose-related manner. For the high-dose group, which corresponded to a time-weighted average dose of 160 mg/kg per day for 104 weeks, there was a 14% incidence of renal tubular adenomas and adenocarcinomas, vs 1% in the control group. This compares to a 24% incidence observed when 180 mg/kg per day of chloroform was administered for 78 weeks in earlier studies. In contrast, chloroform in the drinking water of mice failed to increase the incidence of hepatocellular carcinomas in female B6C3F1 mice. The highest dose group received a time-weighted average dose of 263 mg/kg for 104 weeks, resulting in a 5% combined incidence of hepatocellular adenoma and carcinoma relative to a 6% incidence in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Carcinogenicity of chloroform in drinking water to male Osborne-Mendel rats and female B6C3F1 mice. 404 98

Allyl glycidyl ether is used as a resin intermediate and as a stabilizer of chlorinated compounds, vinyl resins, and rubber. NTP Toxicology and Carcinogenesis studies were conducted by exposing groups of Osborne-Mendel rats and B6C3F1 of each sex to allyl gylcidyl ether (greater than 97% pure) by inhalation for 6 hours per day, 5 days per week for 2 weeks, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Chinese hamster ovary (CHO) cells, and Drosophila melanogaster. Studies of reproductive effects were conducted in rats and mice exposed to allyl glycidyl ether for 8 weeks. Two-Week Studies: Exposure concentrations ranged up to 500 ppm in rats and 100 ppm in mice. All rats that were exposed to 500 ppm died; no deaths occurred at the next lower (200 ppm) exposure concentration. All male mice and 3/5 female mice exposed to 100 ppm and 2/5 male mice and 1/5 female mice exposed to 50 ppm died. Compound-related lesions in rats and mice included acute inflammation of the nasal passage and major airways. Eight-Week Studies of Reproductive Effects: Rats were exposed to 0-200 ppm allyl glycidyl ether, and mice were exposed to 0-30 ppm, 6 hours per day, 5 days per week for 8 weeks. The mating performance of exposed male rats was markedly reduced; however, sperm motility and number were not affected. No deficiencies were seen in the reproductive performance of exposed female rats or male or female mice. Thirteen-Week Studies: Exposure concentrations ranged up to 200 ppm for rats and 30 ppm for mice. All rats lived to the end of the studies. The final mean body weights of male rats exposed to 10-200 ppm were 7%-24% lower than that of controls. Clinical signs attributable to irritation of the upper respiratory tract and eyes were seen in exposed animals. Histologic lesions included squamous metaplasia of the nasal passage in all exposure groups (4 ppm, lowest concentration) and involved both the respiratory epithelium and the olfactory epithelium. The lesions were more severe anteriorly and dorsally and with increasing concentration. At 30 ppm and higher, erosion was seen in the nasal passage and squamous metaplasia was seen in the upper airways. There were no compound-related deaths in mice. The final mean body weights of mice exposed to 30 ppm were 12% lower than those of controls for both males and females. Mice exposed to 10 or 30 ppm allyl glycidyl ether had squamous metaplasia of the nasal passage, involving both the respiratory epithelium and the olfactory epithelium, which tended to be more severe in the anterior and dorsal portions of the nasal passage. In mice exposed to 30 ppm, epithelial erosions were also found. Body Weights and Survival in the Two-Year Studies: Two-year studies were conducted by exposing groups of 50 Osborne-Mendel rats and B6C3F1 mice of each sex to 0, 5, or 10 ppm allyl glycidyl ether by inhalation for 6 hours per day, 5 days per week for 102 or 103 weeks. Mean body weights of the exposed rats were within 8% of those of controls throughout the studies. Mean body weights of mice exposed to 5 or 10 ppm were 5%-20% lower than those of controls. Deaths were seen in all groups of male rats beginning at 1 year of age (final survival-- control, 12/50; 5 ppm, 11/50; 10 ppm, 8/50). Survival of female rats was not exposure related (24/50; 30/50; 25/50). Exposed mice had slightly increased survival (male mice: 38/50; 39/50; 46/50; female mice: 33/50; 42/50; 41/50). Nonneoplastic and Neoplastic Effects in the Two-Year Studies: In male rats exposed to 10 ppm allyl glycidyl ether, three apparently unrelated neoplasms of the nasal passage were found. Two neoplasms, a papillary adenoma and a squamous cell carcinoma, appeared to arise from different cell types in the respiratory epithelium. One poorly differentiated adenocarcinoma in the olfactory region was also found. One papillary adenoma of respiratory epithelial origin was found in a female rat exposed to 5 ppm. Exposure-related nonneoplastic lesions of the nasal passages in rats included inflammation, squamous metaplasiin rats included inflammation, squamous metaplasia, respiratory metaplasia (replacement of olfactory epithelium by ciliated epithelium), hyperplasia of the respiratory epithelium, and degeneration of the olfactory epithelium. In male mice exposed to 10 ppm allyl glycidyl ether, a hemangioma and three papillary adenomas were present in the nasal passage. In female mice exposed to 10 ppm, a hemangioma and an adenoma were found in the nasal passage. Nonneoplastic lesions of the nasal passages in mice included inflammation, squamous metaplasia, hyperplasia, basal cell hyperplasia, dysplasia of the respiratory epithelium, and metaplasia of the olfactory epithelium. In male mice, there was an exposure-related decrease in the incidences of hepatocellular neoplasms; in female mice, there was a decrease in the incidences of pituitary gland adenomas. Genetic Toxicology: Allyl glycidyl ether was mutagenic in S. typhimurium strains TA100 and TA1535 with and without exogenous metabolic activation; no mutagenic activity was observed in strains TA98 or TA1537. Allyl glycidyl ether induced sister chromatid exchanges and chromosomal aberrations in CHO cells both in the presence and the absence of metabolic activation. A significant increase in sex-linked recessive lethal mutations was recorded in the germ cells of male D. melanogaster fed a sucrose solution containing allyl glycidyl ether, but no increase in reciprocal translocations occurred in these cells. Conclusions: Under the conditions of these 2-year inhalation studies, there was equivocal evidence of carcinogenic activity of allyl glycidyl ether for male Osborne-Mendel rats, based on the presence of one papillary adenoma of respiratory epithelial origin, one squamous cell carcinoma of respiratory epithelial origin, and one poorly differentiated adenocarcinoma of olfactory epithelial origin, all occurring in the nasal passage of males exposed to 10 ppm. There was no evidence of carcinogenic activity of allyl glycidyl ether for female rats. One papillary adenoma of the respiratory epithelium was present in a female rat exposed to 5 ppm. There was some evidence of carcinogenic activity of allyl glycidyl ether for male B6C3F1 mice, based on the presence of three adenomas of the respiratory epithelium, dysplasia in four males, and focal basal cell hyperplasia of the respiratory epithelium in seven males in the nasal passage of mice exposed to 10 ppm. There was equivocal evidence of carcinogenic activity of allyl glycidyl ether for female mice, based on the presence of one adenoma of the respiratory epithelium and focal basal cell hyperplasia of the respiratory epithelium in seven females exposed to 10 ppm. The sensitivity of the assay to detect potential carcinogenicity may have been reduced in male rats because of poor survival in all groups. In exposed mice, body weights were decreased 10% or more, mortality was decreased, and there were lower incidences of liver neoplasms (males) and pituitary gland adenomas (females) compared with controls. Significant exposure-related nonneoplastic lesions were restricted to the nasal passage in both rats and mice and induced inflammation, metaplasia, respiratory epithelial hyperplasia, and olfactory epithelial degeneration. Basal cell hyperplasia and dysplasia of the respiratory epithelium of the nasal passage were found only in the mice. Synonyms: allyl 2,3-epoxypropyl ether; 1-allyloxy-2,3-epoxypropane; 1,2-epoxy-3-allyloxypropane; glycidyl allyl ether; ((2-propenyloxy)methyl)oxirane; 1-(allyloxy)-2,3-epoxypropane
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PMID:NTP Toxicology and Carcinogenesis Studies of Allyl Glycidyl Ether (CAS No. 106-92-3) in Osborne-Mendel Rats and B6C3F1 Mice (Inhalation Studies). 1269 45

Toxicology and carcinogenesis studies of dichlorvos (99% pure), a contact and stomach poison for control of insects and parasites, were conducted by administering dichlorvos in corn oil by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 13 weeks or 2 years. Previous feed studies were done by the National Cancer Institute using Osborne-Mendel rats and B6C3F1 mice. Thirteen-Week Studies: Thirteen-week studies with groups of 10 rats of each sex were conducted at doses of 0, 2, 4, 8, 16, 32, or 64 mg/kg dichlorvos in corn oil. All rats that received 32 or 64 mg/kg dichlorvos and 4/10 females that received 16 mg/kg died before the end of the studies. Final mean body weights of dosed and vehicle control rats were similar. Thirteen-week studies with groups of 10 mice of each sex were conducted at doses of 0, 5, 10, 20, 40, 80, or 160 mg/kg. All 10 male mice and 9/10 female mice that received 160 mg/kg and 5/10 male mice that received 80 mg/kg dichlorvos died before the end of the studies. Final mean body weights of dosed and vehicle control mice were similar. No compound-related gross or microscopic pathologic effects were observed in rats or mice. Two-year studies of dichlorvos were conducted by administering 0, 4, or 8 mg/kg dichlorvos, 5 days per week for 103 weeks, to groups of 50 F344/N rats of each sex. Groups of 50 male B6C3F1 mice were administered 0, 10, or 20 mg/kg dichlorvos on the same schedule, and groups of 50 B6C3F1 female mice were administered 0, 20, or 40 mg/kg dichlorvos. Body Weight and Survival in the Two-Year Studies: Mean body weights of dosed and vehicle control rats and mice were similar. No significant differences in survival were observed between any groups of rats or mice of either sex (rats--male: vehicle control, 31/50; low dose, 25/50; high dose, 24/50; female: 31/50; 26/50; 26/50; mice-- male: 35/50; 27/50; 29/50; female: 26/50; 29/50; 34/50). Neoplastic Effects in the Two-Year Studies: Adenomas of the exocrine pancreas occurred at greater incidences in dosed rats than in vehicle controls (male: vehicle control, 25/50; low dose, 30/49; high dose, 33/50; female: 2/50; 3/47; 6/50). Mononuclear cell leukemia in both dosed groups of male rats occurred more frequently than in vehicle controls (11/50; 20/50; 21/50). Mammary gland fibroadenomas and fibroadenomas or adenomas (combined) in dosed female rats occurred at increased incidences relative to the vehicle controls (9/50; 19/50; 17/50). Multiple fibroadenomas occurred in dosed female rats but not in vehicle controls (0/50; 6/50; 3/50); carcinomas occurred in two vehicle control and two low dose female rats. In mice, incidences of squamous cell papillomas of the forestomach were increased in the high dose groups compared with those in the vehicle controls (male: 1/50; 1/50; 5/50; female: 5/49; 6/49; 18/50). Two high dose female mice developed forestomach squamous cell carcinomas. Genetic Toxicology: Dichlorvos was mutagenic in Salmonella typhimurium strain TA100 with and without metabolic activation but was not mutagenic in strain TA98. Dichlorvos was mutagenic in the mouse lymphoma L5178Y/TK+/- assay without metabolic activation. Dichlorvos induced sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells in the absence and presence of metabolic activation. Conclusions: Under the conditions of these 2-year gavage studies, there was some evidence of carcinogenic activity of dichlorvos for male F344/N rats, as shown by increased incidences of adenomas of the exocrine pancreas and mononuclear cell leukemia. There was equivocal evidence of carcinogenic activity of dichlorvos for female F344/N rats, as shown by increased incidences of adenomas of the exocrine pancreas and mammary gland fibroadenomas. There was some evidence of carcinogenic activity of dichlorvos for male B6C3F1 mice, as shown by increased incidences of forestomach squamous cell papillomas. There was clear evidence of carcinogenic activity of dichlorvos for female B6C3F1 mice, as shown by increased incidences of forestomach squamous cell papils cell papillomas. Synonyms: 2,2-dichloroethenyl dimethyl phosphate; 2,2-dichlorovinyl dimethyl phosphate; O,O-dimethyl-O-(2,2-dichlorovinyl)phosphate; DDVP Trade Names: BAY-19149; DDVF; ENT-20738; OMS-14; SD 1750; Canogard®.; Crossman's Fly-Cake®.; Dedevap®.; De-Pester Insect Strip®.; Estrosol®.; Herkol®.; Kill-fly Resin Strip®.; Lethalaire®.; Mafu®.; Misect®.; Nogos®.; Nuvan®.; No-Pest Strip®.; Oko®.; Phoracide®.; Phosvit®.; Vapona®.; Vaponicide®.; Vaporette Bar®. Anthelmintics: Atgard®.; Dichlorman®.; Equigard®.; Task®.
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PMID:NTP Toxicology and Carcinogenesis Studies of Dichlorvos (CAS No. 62-73-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1272 83

Bioassays of technical-grade DDT, TDE, and p,p'-DDE for possible carcinogenicity were conducted using Osborne-Mendel rats and B6C3F1 mice. Each compound was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each species and sex were placed on test as controls for the bioassay of each compound. The time-weighted average high and low dietary concentrations of DDT were, respectively, 642 and 321 ppm for male rats, 420 and 210 ppm for female rats, 44 and 22 ppm for male mice, and 175 and 87 ppm for female mice. The time-weighted average high and low dietary concentrations of TDE were, respectively, 3,294 and 1,647 ppm for male rats, 1,700 and 850 ppm for female rats, and 822 and 411 ppm for male and female mice. The time-weighted average high and low dietary concentrations of DDE were, respectively, 839 and 437 ppm for male rats, 462 and 242 ppm for female rats, and 261 and 148 ppm for male and female mice. After the 78-week dosing period there was an additional observation period of up to 35 weeks for rats and 15 weeks for mice. There were significant positive associations between increased chemical concentration and accelerated mortality in female mice dosed with DDT and in both sexes of rats and in female mice dosed with DDE. This association was not demonstrated in other groups. There was, however, poor survival among control and dosed male mice used in the bioassays of DDT and DDE. In all cases adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. When those male rats receiving TDE and their controls were combined within each group so that the numerators of the tumor incidences represented those animals with either a follicular-cell carcinoma or a follicular-cell adenoma of the thyroid, the incidence in the low dose group was significantly higher than that in the controls. There was a significant positive association between the concentration of DDE administered and the incidences of hepatocellular carcinomas in male and female mice. Among dosed rats and mice no other neoplasms occurred in statistically significant incidences when compared to their respective control groups. Under the conditions of these bioassays there was no evidence for the carcinogenicity of DDT in Osborne-Mendel rats or B6C3F1 mice, of TDE in female Osborne-Mendel rats or B6C3F1 mice of either sex, or of p,p'-DDE in Osborne-Mendel rats, although p,p'-DDE was hepatotoxic in Osborne-Mendel rats. The findings suggest a possible carcinogenic effect of TDE in male Osborne-Mendel rats, based on the induction of combined follicular-cell carcinomas and follicular-cell adenomas of the thyroid. Because of the variation of these tumors in control male rats in this study, the evidence does not permit a more conclusive interpretation of these lesions. p,p'-DDE was carcinogenic in B6C3F1 mice, causing hepatocellular carcinomas in both sexes.
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PMID:Bioassays of DDT, TDE, and p,p'-DDE for possible carcinogenicity. 1279 61

A bioassay of technical-grade chlorobenzilate for possible carcinogenicity was conducted using Osborne-Mendel rats and B6C3F1 mice. Chlorobenzilate was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Chlorobenzilate was administered for 78 weeks followed by an observation period of 12 or 13 additional weeks in mice and 32 or 33 additional weeks in rats. The time-weighted average dietary concentrations of chlorobenzilate were 2,995 and 1,600 ppm for high and low dose male rats, respectively, and 2,229 and 1,175 ppm for high and low dose female rats. Mice received time-weighted average high and low dietary concentrations of 7,846 and 4,231 ppm, respectively, for males and 5,908 and 3,200 ppm, respectively, for females. Survival in both species was high (over 68 percent of the high dose rats and over 82 percent of the high dose mice survived on test until the end of the study). Dose-related mean body weight depression, observed in both species, indicated that the maximum dose for optimal bioassay sensitivity was used in the high dose groups. An increased incidence of hepatocellular carcinomas was observed in dosed mice, i.e., 4/19 (21 percent) in control males, 32/48 (67 percent) in low dose males, 22/45 (49 percent) in high dose males, 0/20 in control females, 11/49 (22 percent) in low dose females, and 13/50 (26 percent) in high dose females. There was a statistically significant positive association between the administration of chlorobenzilate and the appearance of cortical adenoma of the adrenal gland in low dose male and high dose female rats. Although suggestive, the findings of a low incidence of benign adrenal tumors was not considered sufficient evidence to establish the carcinogenicity of chlorobenzilate for the Osborne-Mendel rat. Under the conditions of this bioassay, orally administered chlorobenzilate was carcinogenic in male and female B6C3F1 mice, causing an increased incidence of hepatocellular carcinomas. The results do not, however, provide sufficient evidence for the carcinogenicity of chlorobenzilate in Osborne-Mendel rats.
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PMID:Bioassay of chlorobenzilate for possible carcinogenicity. 1283 Feb 22

A bioassay of technical-grade chloropicrin for possible carcinogenicity was conducted using Osborne-Mendel rats and B6C3F1 mice. Chloropicrin in corn oil was administered 5 days a week by gavage, at either of two dosages, to groups of 50 male and 50 female animals of each species. Time-weighted average dosages of 25 mg/kg/day for low dose male rats and 20 mg/kg/day for low dose female rats were administered during weeks 1 through 33, then administered cyclically (1 dose-free week followed by 4 weeks of administration) from weeks 34 through 78. Time-weighted average dosages of 26 mg/kg/day for high dose male rats and 22 mg/kg/day for high dose female rats were administered from weeks 1 through 17, weeks 31 through 33, and cyclically (1 dose-free week followed by 4 weeks of administration) during weeks 34 through 78. Time-weighted average dosages of 66 and 33 mg/kg/day, respectively, for male and female mice were administered for 78 weeks. These dosing regimens were followed by observation periods of 32 weeks for rats and 13 weeks for mice. For each species, 20 animals of each sex were placed on test as vehicle controls. These animals were gavaged with corn oil. Twenty animals of each sex were placed on test as untreated controls for each species. These animals were not gavaged. A high incidence of early death was observed among chloropicrin-dosed rats. Deaths among dosed rats occurred as early as week 1 for females and week 6 for males. Median survival was week 48 for high dose males, week 54 for low dose males, week 70 for high dose females and week 59 for low dose females. Statistical tests indicate a positive association between chloropicrin dosage and mortality of rats. No neoplasms were observed at higher incidences in dosed than control rats. In rats of both sexes, incidences of adenoma of the pituitary and of adenocarcinoma or fibroadenoma of the mammary gland were higher in control groups than dosed groups. It is likely that most dosed rats did not survive long enough to be at risk from late-appearing tumors. A rapid decrease in survival after the first year of the study was observed among high dose mice of both sexes. Survival of high dose male mice decreased from 80 percent in week 54 to 26 percent in week 90. Survival of high dose female mice decreased from 82 percent in week 54 to 36 percent in week 90. Statistical tests indicated a positive association between chloropicrin dosage and mortality of mice. In chloropicrin-dosed mice, proliferative lesions of the squamous epithelium of the forestomach included two carcinomas and a papilloma. Although these tumors were uncommon in control animals, statistical analysis did not demonstrate that they were related to administration of chloropicrin. Other proliferative lesions of the forestomach occurring at an increased incidence in dosed mice were acanthosis and hyperkeratosis. No statistically significant increase of tumor incidence was observed in mice. The bioassay of chloropicrin using Osborne-Mendel rats did not permit an evaluation of carcinogenicity because of the short survival time of dosed animals. The bioassay of chloropicrin using B6C3F1 mice did not provide conclusive statistical evidence for the carcinogenicity of this compound.
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PMID:Bioassay of chloropicrin for possible carcinogenicity. 1283 Feb 32

A bioassay of dieldrin-free photodieldrin (synthesized by Gulf South Research Institute) for possible carcinogenicity was conducted by administering the test material in feed to Osborne-Mendel rats and B6C3F1 mice. Groups of 50 rats of each sex were initially administered photodieldrin at one of two doses, either 5 or 10 ppm. Because of neurotoxic signs, doses in the females were reduced after 30 weeks. Total periods of treatment for low- and high-dose males and low-dose females were 80 weeks, followed by periods of 31 or 32 weeks of additional observation; the total period of treatment for the high-dose females was 59 weeks, followed by a period of additional observation of 53 weeks. The time-weighted average doses for the females were 3.4 or 7.5 ppm. Matched controls consisted of 10 untreated rats of each sex; pooled controls, used for statistical evaluation, consisted of the matched controls combined with 65 untreated male and 65 untreated female rats from similarly performed bioassays of six other test chemicals. All surviving rats were killed at 111-112 weeks. Groups of 50 mice of each sex were administered photodieldrin at one of two doses, either 0.32 or 0.64 ppm, for 80 weeks, then observed for an additional 13 weeks. Matched controls consisted of groups of 10 untreated mice of each sex at each dose; pooled controls, used for statistical evaluation, consisted of the matched controls combined with 60 untreated male and 60 untreated female mice from similarly performed bioassays of six other test chemicals. All surviving mice were killed at 93 weeks. Mean body weights attained by low- and high dose male and female rats and mice were essentially unaffected by photodieldrin. Convulsions and hyperactivity were noted in treated male and female rats and in male mice. Mortality rates of either sex or either species were not affected by treatment. In rats, benign tumors (adenoma and fibroadenoma) of the mammary gland in females showed a dose-related trend (P=0.039) compared with matched, but not pooled, controls (8/72 pooled controls, 0/9 matched controls, 5/50 low-dose, 10/49 high-dose). Adenocarcinoma of the mammary gland occurred in two additional low-dose females. The incidences of these tumors in either of the treated groups were not significantly higher than those in the control groups using either matched or pooled controls. Three papillary and follicular-cell adenomas and one papillary adenocarcinoma of the thyroid occurred in the low-dose females, giving a statistically significant increase over the pooled controls (P=0.022), but these thyroid tumors did not occur in the high-dose animals. The dose-related trend was not statistically significant using either pooled or matched controls, and the incidence in the low-dose group is not greater than that in the historical controls. In male rats, the incidence of hemangiomas showed a statistically significant dose-related trend (P=0.021) using pooled controls, but the direct comparison of the three hemangiomas in the high-dose group with the pooled-control group was not statistically significant. Furthermore, three hemangiomas is a small number, and the tumors occurred in more than one anatomic site (two in the spleen, one in subcutaneous tissue). The occurrence of these tumors cannot clearly be associated with treatment. In mice, there were no tumors that were statistically significant in treated groups of either sex. It is concluded that under the conditions of this bioassay, photodieldrin was not carcinogenic for Osborne-Mendel rats or B6C3F1 mice.
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PMID:Bioassay of photodieldrin for possible carcinogenicity. 1284 50

A bioassay of technical-grade tetrachlorvinphos for possible carcinogenicity was conducted by administering the test chemical in feed to Osborne-Mendel rats and B6C3F1 mice. Groups of 50 rats of each sex were administered tetrachlorvinphos at one of two doses for 80 weeks, then observed for 31 additional weeks. Time-weighted average doses were either 4,250 or 8,500 ppm. Matched controls consisted of groups of 10 untreated rats of each sex; pooled controls, used for statistical evaluation, consisted of the matched controls combined with 45 untreated male and 45 untreated female rats from similar bioassays of four other test chemicals. All surviving rats were killed at 111 weeks. Groups of 50 mice of each sex were administered tetrachlorvinphos at one of two doses, either 8,000 or 16,000 ppm, for 80 weeks, then observed for 12 additional weeks. Matched controls consisted of groups of 10 untreated mice of each sex; pooled controls, used for statistical evaluation, consisted of the matched controls combined with 40 untreated male and 40 untreated female mice from similar bioassays of four other test chemicals. All surviving mice were killed at 90-92 weeks. The mean body weights of the treated rats and mice were generally lower than those of the matched controls; however, the mortality rate was affected adversely by tetrachlorvinphos only in the male rats. Survival of all groups of rats and mice was adequate for meaningful statistical analyses of the incidence of tumors, except for a matched-control group of female rats for which the survival was abnormally low. In rats, C-cell adenoma of the thyroid showed a significant dose-related trend in the females, using pooled controls (controls 1/46, low-dose 2/50, high-dose 7/46, P=0.013), and by direct comparison, an increased incidence in the high-dose group (P=0.027). High incidences of C-cell hyperplasia in treated males and females further indicated a chemical-related effect on proliferative lesions of the thyroid. Cortical adenoma of the adrenal also showed a significant dose-related trend in the females, using pooled controls (controls 0/50, low-dose 2/49, high-dose 5/50,P=0.017), and by direct comparison, an increased incidence in the high-dose group (P=0.022). Hemangioma of the spleen occurred in male rats at a significantly higher incidence in the low-dose group than in the pooled controls (controls 0/52, low-dose 4/48, P=0.049); however, neither the incidence in the high-dose group (0/47) nor the test result for dose-related trend was statistically significant. In mice, hepatocellular carcinoma in males showed a highly significant dose-related trend, using either matched controls (controls 0/9, low-dose 36/50, high-dose 40/50, P<0.001) or pooled controls (controls 5/49, P<0.001). This finding was supported by direct comparisons of low- and high-dose groups of males with matched- or pooled-control groups, which showed highly significant increases in incidences of the tumor in the treated groups in all instances (P<0.001). In females, the incidence of hepatocellular carcinoma was not significant; however, the incidence of neoplastic nodule was significantly higher in both the low- and high-dose groups than in the pooled controls (controls 1/48, low-dose 14/49, P<0.001; high-dose 9/47, P=0.007), using pooled controls for tests for both doses. Because of this higher incidence in the low-dose group than in the high-dose group, there was a significant departure from linear trend (P=0.006). Granulomatous lesions of the liver were found in high proportions in both treated rats and treated mice, but none were found in matched controls. It is concluded that under the conditions of this bioassay, the administration of technical-grade tetrachlorvinphos in Osborne-Mendel rats was associated with proliferative lesions of the C cells of the thyroid and cortical adenomas of the adrenal in females. In female B6C3F1 mice, the incidence of neoplastic nodule of the liver was associated with treatment, and in male mice tetrachlorvinphos was carcinogenic, causing hepatocellular carcinoma of the liver.
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PMID:Bioassay of tetrachlorvinphos for possible carcinogenicity. 1284 74

A bioassay of technical-grade malathion for possible carcinogenicity was conducted by administering the test chemical in feed to Osborne-Mendel rats and B6C3F1 mice. Groups of 50 rats of each sex were administered malathion at one of two doses for 80 weeks, then observed for 33 weeks. Time-weighted average doses were 4,700 or 8,150 ppm. Matched controls consisted of groups of 15 untreated rats of each sex; pooled controls consisted of the matched controls combined with 40 untreated male and 40 untreated female rats from similar bioassays of four other test chemicals. All surviving rats were killed at 108-113 weeks. Groups of 50 mice of each sex were administered malathion at one of two doses, either 8,000 or 16,000 ppm, for 80 weeks, then observed for 14 or 15 weeks. Matched controls consisted of groups of 10 untreated mice of each sex; pooled controls consisted of the matched controls combined with 40 untreated male and 40 untreated female mice from similar bioassays of four other test chemicals. All surviving mice were killed at 94 or 95 weeks. Mortality in either rats or mice was not significantly related to the administration of malathion. Sufficient numbers of animals were at risk in the dosed and control groups of rats and mice of each sex for development of late-appearing tumors. In female rats, three follicular-cell carcinomas and one follicular-cell adenoma of the thyroid occurred in the high-dose group, and three follicular-cell hyperplasias occurred in the low-dose group. The incidence of these tumors showed a statistically significant (P=0.026) dose-related trend; however, the results of the Fisher exact test for direct comparison between the dosed and control groups were not significant. More dosed males than dosed females had either tumors or hyperplasia of the follicular cells of the thyroid; however, because of the higher incidence of tumors among the male controls, none of the results of the statistical tests were significant. These thyroid tumors were not considered to be associated with the administration of malathion. In male mice, hepatocellular carcinoma occurred at the following incidences: matched controls 2/10, pooled controls 5/49, low-dose 7/48, high-dose 11/49. In addition, neoplastic nodules occurred in 3/49 pooled-control and 6/49 high-dose animals. When the combined incidence of these neoplasms in the dosed animals was compared with that of the pooled controls, the dose-related trend was P=0.019 and the direct comparison of the high-dose group with the control group was P=0.031. Thus, none of the direct comparisons of dosed groups with controls were significant using the Bonferroni criteria. In addition, the historical controls from this laboratory had several control groups with incidences of 35-40% hepatocellular carcinoma, rates which are comparable with the incidence of this tumor in the dosed male mice of the present study. Thus, these liver tumors are not considered to be associated with the administration of malathion. The incidences of liver tumors in dosed females were not statistically significant when compared with that in control animals. It is concluded that under the conditions of this bioassay, there was no clear evidence of the association of the tumor incidence with the administration of malathion to Osborne-Mendel rats or B6C3F1 mice.
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PMID:Bioassay of malathion for possible carcinogenicity. 1284 84


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