National Cancer Institute carcinogenesis technical report series最新文献

A bioassay of 4-chloro-o-toluidine hydrochloride for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were administered 4-chloro-o-toluidine in the diet at one of two doses, either 1,250 or 5,000 ppm, for 107 weeks. Groups of 50 mice of each sex were administered the test chemical in the diet at one of two doses, either 3,750 or 15,000 ppm for the males and either 1,250 or 5,000 ppm for females, for 99 weeks, except for the high dose females (92 weeks). Matched controls consisted of 20 untreated rats and 20 untreated mice of each sex. All surviving animals were killed at the end of administration of the test chemical. Mean body weights of the high-dose rats and the low- and high-dose mice of each sex were lower than those of corresponding controls, and those of the mice were dose related. Mortality was not significantly affected by administration of the test chemical to rats of either sex and survival was 75% or greater at the end of the study in dosed and control groups. Sufficient numbers of rats were at risk for the development of late-appearing tumors. In mice, mortality was dose related for each sex. In rats no tumors occurred at incidences which could clearly be related to administration of the test chemical. In both male and female mice, hemangiosarcomas occurred at incidences that were dose related (P

A bioassay of sulfisoxazole for possible carcinogenicity was conducted by administering the chemical by gavage to Fischer 344 rats and B6C3F1 mice. Groups of 50 rats of each sex and 50 mice of each sex were administered sulfisoxazole suspended in aqueous 0.5% carboxymethyl cellulose 7 days per week at one of two doses, either 100 or 400 mg/kg body weight for the rats and either 500 or 2,000 mg/kg for the mice. Vehicle controls consisted of groups of 50 rats of each sex and 50 mice of each sex that were administered only the aqueous 0.5% carboxymethyl cellulose. Untreated controls consisted of groups of 50 rats of each sex and 50 mice of each sex. The dosed groups of the rats and mice were administered the chemical by gavage for 103 weeks, then observed for 1 to 3 additional weeks; the vehicle-control groups were similarly administered 0.5% carboxymethyl cellulose alone. All surviving rats and mice were killed at weeks 104 to 106. Mean body weights of high-dose male rats and female mice were slightly lower than those of corresponding vehicle controls during the last 40 to 50 weeks of the bioassay; mean body weights of dosed female rats and male mice were unaffected. Survival rates were unaffected by the test chemical, and adequate numbers of animals were at risk for the development of late-appearing tumors. No tumors occurred in the dosed groups of rats or mice of either sex at incidences that were significantly higher than those of the vehicle-control groups. It is concluded that under the conditions of this bioassay, sulfisoxazole was not carcinogenic for either Fischer 344 rats or B6C3F1 mice

The bioassay of nithiazide for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. Nithiazide was administered in the diet, at either of two concentrations, to groups of 50 male and 50 female animals of each species. The high and low concentrations of nithiazide utilized were, respectively, 1,250 and 625 ppm for rats and 5,000 and 2,500 ppm for mice. Dosed rats received feed containing nithiazide for 38 weeks, and as a result of a shortage of nithiazide, the animals were not fed the dosed feed for the next 9 weeks. The dosed feed diet was then resumed and continued for 56 weeks, after which time a 1-week observation period followed. Dosed mice received feed containing nithiazide for 61 weeks and, due to a shortage of nithiazide, the animals were not fed dosed feed for the next 9 weeks. The dosed feed diet was then resumed and continued for 33 weeks, followed by a 1-week observation period. Twenty animals of each sex and species were placed on test as controls. In both species, adequate numbers of animals survived sufficiently long to be at risk from late-developing tumors. There was no significant positive association between dosage and mortality for either rats or mice. Compound-related mean body weight depression occurred in both sexes of each species. Statistically significant incidences of hepatocellular adenomas and carcinomas were found in high dose male mice but not in female mice. Although the increased incidences of these tumors in dosed female mice were not statistically significant, the evidence presented was strongly suggestive of carcinogenicity to the liver in female B6C3F1 mice. Statistically significant increased incidences of a combination of mammary and skin fibroadenomas and cystadenomas NOS were found in the high dose female rats. No unusual tumors were observed in either species. Under the conditions of this bioassay, nithiazide was carcinogenic in male and probably female B6C3F1 mice, causing a combination of hepatocellular carcinomas and hepatocellular adenomas. Nithiazide was also carcinogenic in female Fischer 344 rats, causing an increase in the incidence of mammary neoplasms. The compound was not carcinogenic in male Fischer 344 rats.

A bioassay of (2-chloroethyl)trimethylammonium chloride for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were administered either 1,500 or 3,000 ppm of the compound for 108 weeks, and 50 mice of each sex were administered 500 or 2,000 ppm for 102 weeks. Matched controls consisted of 20 untreated and 20 untreated mice of each sex. All surviving animals were killed at the end of the period of administration of the test chemical. Mean body weights of dosed rats and mice were lower than those of corresponding controls for part or all of the bioassay, except for the dosed male mice, whose mean body weights were essentially the same as those of the corresponding controls. Survival was not affected significantly in any of the dosed groups of rats or mice and was at least 64% in every dosed or control group of each species at the end of the bioassay. Sufficient numbers of dosed and control rats and mice of each sex were at risk for the development of late-appearing tumors. Since there was virtually no decrease in mean body weight in dosed male mice and only a slight decrease in female mice, and since there were no other toxic signs and no dose-related mortality, the animals may have been able to tolerate higher doses. No tumors occurred in the rats or mice of either sex at incidences that could be associated with administration of the test chemical. It is concluded that under the conditions of this bioassay, (2-chloroethyl)trimethylammonium chloride was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

A bioassay of technical-grade ethyl tellurac for possible carcinogenicity was conducted by administering the preparation in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were administered ethyl tellurac at one of two doses, either 300 or 600 ppm for the males and either 150 or 300 ppm for the females, for 105 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at 105 weeks. Groups of 50 mice of each sex were administered ethyl tellurac at one of two doses, initially either 2,500 or 5,000 ppm. Due to signs of toxicity in the dosed animals, these doses were reduced to 500 and 2,000 ppm, respectively, starting at week 41 for the males and at week 38 for the females. The reduced doses were maintained for 66 weeks for the males; for the females, the reduced doses were raised after 3 weeks to 2,000 and 5,000 ppm, respectively, and maintained at these levels for 66 weeks. The time-weighted average doses for the males were either 1,255 or 3,132 ppm; for the females, either 2,132 or 4,915 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at 106 weeks. Mean body weights of the dosed groups of rats or mice were lower than those of corresponding controls throughout most or all of the bioassay. No other clinical signs in the rats or mice were clearly related to administration of the test chemical. Survival of the rats and the mice was not affected by the chemical, and sufficient numbers of all groups were at risk for the development of late-appearing tumors. In the male rats, mesotheliomas occurred at incidences that were dose related (P=0.012); in direct comparisons, the incidences of the tumors in the individual dosed groups were not significantly higher than that in the control group (controls 0/20, low-dose 2/49, high-dose 8/50). However, the historical-control data at this laboratory indicate an incidence of 12/416 (2.9%) in male F344 rats compared with 8/50 (16%) in the male high-dose group in this study. In the female rats, no tumors occurred at incidences that were related to administration of the test chemical. In both male and female mice, adenomas of the lacrimal (harderian) gland of the eye occurred in the dosed groups, but not in the corresponding controls (males: controls 0/17; low-dose 16/46, high-dose 10/49; females: controls 0/20, low-dose 6/50, high-dose 5/49). The incidences in the dosed groups were not high enough to show statistically significant dose-related trends. However, in direct comparisons of dosed and control groups of male mice, the incidence was statistically significant in the low-dose males (P=0.003). In female mice, direct comparisons of dosed and control groups indicated that the incidence of this tumor was not statistically significant. It is concluded that under the conditions of this bioassay, ethyl tellurac was not carcinogenic for F344 rats or B6C3F1 mice of either sex. The incidence of mesotheliomas i

A bioassay of technical-grade tetraethylthiuram disulfide for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were administered tetraethylthiuram disulfide in the diet at one of two doses, either 300 or 600 ppm, for 107 weeks. Groups of 50 mice of each sex were administered the test chemical at one of two doses, either 500 or 2,000 ppm for the males and either 100 or 500 ppm for the females, for 108 weeks. Matched controls consisted of 20 untreated rats and 20 untreated mice of each sex. All surviving animals were killed at the ends of the periods of administration of the test chemical. Mean body weights of the dosed rats and mice of each sex were lower than those of corresponding controls and were dose related throughout most of the bioassay. Mortality was not significantly affected by administration of the test chemical to either the rats of the mice, except for the female rats, in which the mortality was higher in the control group than in the dosed groups; however, the survival at the end of the bioassay was 65% or greater in all dosed and control groups of rats and mice of either sex, and sufficient numbers of animals were at risk in each group for the development of late-appearing tumors. No tumors occurred in the rats or mice of either sex at incidences that were significantly higher in dosed groups than in corresponding control groups. It is concluded that under the conditions of this bioassay, tetraethylthiuram disulfide was not carcinogenic for F344 rats or B6C3F1 mice of either sex.

A bioassay of fenthion for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex and 50 mice of each sex were administered fenthion in the diet at one of two doses, either 10 or 20 ppm, for 103 weeks and then observed for 0 to 2 additional weeks. Matched controls consisted of groups of 25 untreated animals of each species and sex. All surviving animals were killed at 103 to 105 weeks. The mean body weights and the survival of the dosed animals were essentially unaffected by administration of the test chemical with the exception of the survival of the low-dose male mice, which was significantly lower than that of the corresponding matched control. Thus, most of the animals may have been able to tolerate higher doses. Sufficient numbers of animals in all groups of rats and mice were at risk for development of late-appearing tumors. In the male and female rats and the female mice, no tumors occurred at incidences that were significantly higher in dosed groups than in control groups. In the male mice, sarcomas, fibrosarcomas, or rhabdomyosarcomas of the integumentary system occurred at incidences that were dose related (P=0.043). In direct comparisons of the incidences of these tumors in the dosed groups with the incidence in the control group, the P values of 0.048 and 0.028 for the low- and high-dose groups, respectively, did not meet the Bonferroni criterion of P=0.025 for significance when multiple comparisons are made (controls 0/25, low-dose 7/49 or 14%, high-dose 8/48 or 17%). However, the incidence of sarcomas and fibrosarcomas in historical-control male B6C3F1 mice used in bioassays of other chemicals tested at this laboratory was 7/435 (1.6%), and no rhabdomyosarcomas occurred in the historical-control male mice. It is concluded that under the conditions of this bioassay, fenthion was not carcinogenic for male or female F344 rats or for female B6C3F1 mice. The increased incidence of sarcomas, fibrosarcomas, and especially rhabdomyosarcomas of the integumentary system in the male B6C3F1 mice suggested that the test chemical was carcinogenic in these animals.

A bioassay of coumaphos for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex and 50 mice of each sex were administered the coumaphos in the diet at one of two doses, either 10 or 20 ppm, for 103 weeks and then observed for 0-1 additional weeks. Matched controls consisted of groups of 25 untreated animals of each species and sex. All surviving animals were killed at 103-105 weeks. Mean body weights of the dosed female rats were lower than those of corresponding controls, while mean body weights of dosed male rats and of dosed male and female mice were essentially unaffected. No clinical signs that are typical of organophosphorus poisoning were reported in either rats or mice. Survival of the rats and mice was not affected by administration of the test chemical. The test animals may have been able to tolerate higher doses. Sufficient numbers of animals in all groups of the rats and mice were at risk for the development of late-appearing tumors. In both rats and mice, no tumors occurred in the dosed groups of either sex at incidences that were significantly higher than those in corresponding control groups. It is concluded that under the conditions of this bioassay, coumaphos was not carcinogenic for either F344 rats or B6C3F1 mice.

Endrin is an organochlorine pesticide having a structural characteristic of the cyclodiene group, which includes aldrin (CAS No. 309-00-2), dieldrin (CAS No. 60-57-1), chlordane (CAS No. 57-74-9), heptachlor (CAS No. 76-44-8), and endosulfan (CAS No. 115-29-7). It is the most acutely toxic compound in the cyclodiene group but is less persistent in the environment than DDT or dieldrin. As an insecticide, it is currently used for small grains, sugarcane, and cotton; as an avicide, for forest seed and perch applications; and as a rodenticide, for forest seed and orchard soil applications. A bioassay of technical-grade endrin 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 one of two doses of endrin for 80 weeks, then observed for 31 or 34 weeks. The doses used for the male rats were 2.5 or 5 ppm. The initial doses of 5 or 10 ppm used for the females were not well tolerated and were reduced during the study. The time-weighted average doses used for the females were 3 or 6 ppm. Matched controls consisted of groups of 10 rats of each sex; pooled controls, used for statistical evaluation, consisted of the matched-control groups combined with 40 untreated male and 40 untreated female rats from similar bioassays of other test chemicals. All surviving rats were killed at 110 to 114 weeks. Groups of 50 mice of each sex were administered endrin at one of two doses for 80 weeks, then observed for 10 or 11 weeks. Initial doses of 2.5 or 5 ppm used for the males were not well tolerated and were reduced during the study. The time-weighted average doses used for the males were 1.6 or 3.2 ppm; the doses used for the females were 2.5 or 5 ppm. Matched controls consisted of groups of 10 mice of each sex; pooled controls, used for statistical evaluation, consisted of the matched-control groups combined with 50 untreated male and 50 untreated female mice from similar bioassays of other test chemicals. All surviving mice were killed at 90 or 91 weeks. The clinical signs observed in both rats and mice indicated that the doses of endrin used were near the maximum tolerated doses. In mice these signs includedhyperexcitability, a manifestation of toxicity of the organochlorine pesticides. However, mean body weights of the rats and mice were not affected by administration of endrin. Although the survival of the high-dose male mice at the end of the study was markedly lower than that of the controls, the survivals of the low- and high-dose female mice and male and female rats were unaffected by the endrin. The survival of the low-dose male mice could not be evaluated, due to the accidental administration of excessive quantities of endrin to this group during week 66. However, a substantial portion of all groups of rats and mice survived to an age at which tumors could be expected to occur. In rats, the combination of adenomas and carcinomas of t

A bioassay for the possible carcinogenicity of 4'-(chloroacetyl)-acetanilide was conducted using Fischer 344 rats and B6C3F1 mice. 4'-(Chloroacetyl)-acetanilide 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 sex and species were placed on test as controls. The high and low dietary concentrations of 4'-(chloroacetyl)-acetanilide were, respectively, 2,000 and 1,000 ppm for rats and 10,000 and 5,000 ppm for mice. The compound was administered for 87 weeks of a 102-week period in rats and for 90 weeks of a 105-week period in mice. Mice were killed at the end of the last week of compound administration, while rats were observed for 1 week after compound administration ceased. There were no significant positive associations between the concentration of 4'-(chloroacetyl)-acetanilide administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Dose-related mean body weight depression was observed for males and females of both species, indicating that the concentrations of 4'-(chloroacetyl)-acetanilide administered to the animals in this bioassay may have approximated the maximum tolerated concentrations. None of the statistical tests for any site in rats of either sex or in male mice indicated a significant positive association between compound administration and tumor incidence. Although there was a significant positive association between the concentration of the compound administered and the incidences of hepatocellular adenomas in female mice, the Fischer exact comparisons were not significant. Under the conditions of this bioassay, 4'-(chloroacetyl)-acetanilide was not carcinogenic when administered in the diet to Fischer 344 rats or B6C3F1 mice of either sex.