Biomedical subjects

National Toxicology Program

Publications and source records attributed to National Toxicology Program.

At least 595 records · Page 33Linked to original sources

PubMed1979

Bioassay of butylated hydroxytoluene (BHT) for possible carcinogenicity.

A bioassay of BHT for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were administered BHT at one of two doses, either 3,000 or 6,000 ppm; the rats for 105 weeks and the mice for 107 or 108 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 dosed rats and mice were lower than those of the corresponding controls and were dose related throughout most of the bioassay. Survival was not affected significantly in the dosed groups of rats or mice, and the survival was 60% or greater in all dosed or control groups of rats and mice of each sex at the end of the bioassay. Sufficient number of animals were at risk for the development of late-appearing tumors. Alveolar/bronchiolar carcinomas or adenomas occurred in the female mice at a significant incidence in the low-dose group (P=0.009) but not in the high dose group, and the incidences were not significantly dose related (control 1/20, low-dose 16/46, high-dose 7/50). Thus, these lung tumors in the female cannot clearly be related to the administration of the BHT. No tumors occurred in either male or female rats at incidences that were significantly higher in dosed groups than in corresponding control groups. Nonneoplastic lesions that may have been related to the administration of the test chemical included focal alveolar histiocytosis at increased incidences in the dosed female rats and various lesions of the liver at increased incidences in the dosed male mice. It is concluded that under the conditions of this bioassay, BHT was not carcinogenic for F344 rats or B6C3F1 mice.

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PubMed1979

Bioassay of N,N'-diethylthiourea for possible carcinogenicity.

A bioassay for the possible carcinogenicity of N,N'-diethylthiourea was conducted using Fischer 344 rats and B6C3F1 mice. N,N'-Diethylthiourea was administered in the feed, at either of two concentrations, to groups of 50 males and 50 females of each species. Twenty animals of each sex and species, except for 19 male mice, were placed on test as controls. The high and low dietary concentrations of N,N'-diethylthiourea were, respectively, 250 and 125 ppm for rats and 500 and 250 ppm for mice. The compound was administered in the diet for 103 weeks, followed by an observation period of 1 week for all dosed groups. There were no significant positive associations between the dosages of N,N'-diethylthiourea administered and mortality in rats or mice of either sex. Adequate numbers of animals in all dose groups survived sufficiently long to be at risk from late-developing tumors. Compound-related mean body weight depression was apparent among dosed male and female mice when compared to their respective controls,indicating that the concentrations of N,N'-diethylthiourea administered to mice may have approximated the maximum tolerated dosages. There were statistically significant elevated incidences of follicular-cell carcinomas of the thyroid in high dose male rats. In addition, there were statistically significant elevated incidences of a combination of thyroid follicular-cell carcinomas and follicular-cell adenomas in high dose male and female rats. Under the conditions of this bioassay, N,N'-diethylthiourea was carcinogenic to Fischer 344 rats, causing follicular-cell carcinomas of the thyroid in males and follicular-cell neoplasms of the thyroid in females. There was no evidence for the carcinogenicity of the compound in B6C3F1 mice.

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PubMed1979

Bioassay of nithiazide for possible carcinogenicity.

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.

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PubMed1979

Bioassay of p-cresidine for possible carcinogenicity.

A bioassay of p-cresidine for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. p-Cresidine was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. The dietary concentrations used in the chronic bioassay for low and high dose rats were 0.5 and 1.0 percent, respectively. The time-weighted average concentrations fed to low dose male, low dose female, high dose male and high dose female mice were 0.22, 0.22. 0.46, and 0.44 percent, respectively. All dosed animals, except for high dose male mice, were administered p-cresidine in the diet for 104 weeks and observed for an additional period of up to 2 weeks. All high dose male mice were dead by the end of week 92. For each species, 50 animals of each sex were placed on test as controls and fed only the basal laboratory diet. Mortality rates were dose-related for both sexes of both species. That incidences of certain tumors were higher in low dose than in high dose groups was probably due to accelerated mortality in the high dose group. In dosed rats of both sexes, statistically significant incidences of bladder carcinomas (combined incidences of papillary carcinomas, squamous-cell carcinomas, transitional-cell papillomas, transitional-cell carcinomas, and undifferentiated carcinomas) and olfactory neuroblastomas were observed. The combined incidence of neoplastic nodules of the liver, hepatocelular carcinomas, or mixed hepato/cholangio carcinomas was also significant in low dose male rats. In both male and female dosed mice, the incidence of bladder carcinomas (combined incidence of carcinomas NOS, squamous-cell carcinomas, and transitional carcinomas) was significant. The incidence of hepatocellular carcinomas was also significant in dosed female mice. Under the conditions of this bioassay, p-cresidine was carcinogenic to Fischer 344 rats, causing increased incidences of carcinomas and of papillomas of the urinary bladder in both sexes, increased incidences of olfactory neuroblastomas in both sexes, and of liver tumors in males. p-Cresidine was also carcinogenic in B6C3F1 mice, causing carcinomas of the urinary bladders in both sexes and hepatocellular carcinomas in females.

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PubMed1979

Bioassay of fenthion for possible carcinogenicity (CAS No. 55-38-9).

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.

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PubMed1979

Bioassay of dl-menthol for possible carcinogenicity.

A bioassay of dl-menthol for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice. Groups of 50 rats of each sex and 50 mice of each sex were administered dl-menthol at one of the following doses, either 3,750 or 7,500 ppm for the rats and either 2,000 or 4,000 ppm for the mice, for 103 weeks, then observed for 1 or 2 additional weeks. Matched controls consisted of 50 untreated rats of each sex and 50 untreated mice of each sex. All surviving rats were killed at 105 weeks and all surviving mice at 104 weeks. Mean body weights of dosed rats and mice were only slightly lower than those of corresponding controls. No other clinical signs related to administration of the dl-menthol were noted in the dosed groups of animals. A dose-related trend in mortality was observed only in the female mice. Survival at the end of the bioassay was at least 62% in all dosed and control groups of animals of each species, and sufficient numbers of animals were at risk for the development of late-appearing tumors. In male rats, no tumors occurred at incidences which were considered to be related to the administration of dl-menthol. In female rats, no tumors occurred at higher incidences in the dosed groups than in the control groups. Fibroadenomas of the mammary gland occurred at lower incidences in the low-dose (10/49) and high-dose (7/49) groups than in the control group (20/50), and alveolar/bronchiolar adenomas or carcinomas of the lung occurred only in the controls (3/50). In mice of either sex, no tumors occurred in dosed groups at incidences that were significantly different from those for corresponding control groups. It is concluded that under the conditions of this bioassay, dl-menthol was not carcinogenic for either Fischer 344 rats or B6C3F1 mice.

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PubMed1979

Bioassay of titanium dioxide for possible carcinogenicity.

A bioassay of titanium dioxide for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice. Groups of 50 rats of each sex and 50 mice of each sex were administered titanium dioxide in the diet at one of two doses, either 25,000 or 50,000 ppm, for 103 weeks and then observed for 1 additional week. Matched controls consisted of 50 untreated rats of each sex and 50 untreated mice of each sex. All surviving rats and mice were killed at 104 weeks. Administration of the titanium dioxide had no appreciable effect on the mean body weights of rats or mice of either sex. With the exception of white feces, there was no other clinical sign that was judged to be related to the administration of titanium dioxide. Survival of the rats and the male mice at the end of the bioassay was not affected by the test chemical; mortality in female mice was dose related. Sufficient numbers of dosed and control rats and mice of each sex were at risk for development of late-appearing tumors. In the female rats, C-cell adenomas or carcinomas of the thyroids occurred at incidences that were dose related (P=0.013), but were not high enough (P=0.043 for direct comparison of the high-dose group with the control group) to meet the level of P=0.025 required by the Bonferroni criterion (controls 1/48, low-dose 0/47, high-dose 6/44). Thus, these tumors of the thyroid were not considered to be related to the administration of the test chemical. In male and female mice, no tumors occurred in dosed groups at incidences that were significantly higher than those for corresponding control groups. It is concluded that under the conditions of this bioassay, titanium dioxide was not carcinogenic by the oral route for Fischer 344 rats or B6C3F1 mice.

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PubMed1979

Bioassay of coumaphos for possible carcinogenicity.

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.

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PubMed1979

Bioassay of parathion for possible carcinogenicity.

A bioassay for possible carcinogenicity of technical-grade parathion was conducted by administering the test chemical in the diet to Osborne-Mendel rats and B6C3F1 mice. Groups of 50 rats of each sex were administered parathion at one of two doses for 80 weeks, then observed for 32 or 33 weeks. Time-weighted average doses for males were 32 or 63 ppm; for females, they were 23 or 45 ppm. All surviving rats were killed at 112 or 113 weeks. Groups of 50 mice of each sex were administered parathion at one of two doses, either 80 or 160 ppm. The low-dose males were administered parathion for 71 weeks; the high-dose males for 62 weeks; and the low- and high-dose females for 80 weeks. The animals were then maintained for observation and all surviving mice were killed at 89 or 90 weeks. Matched controls consisted of groups of 10 untreated rats or mice of each sex; pooled controls of rats or mice taken from similar bioassays of other test chemicals were also used. Mean body weights of high-dose male and female rats and of high- and low-dose male mice were generally lower than those of the matched controls during the period of administration of the chemical. Mean body weights of the other groups of dosed rats and mice did not differ appreciably from those of the matched controls. Since body weights and survival of the female mice were not affected, female mice may have been able to tolerate a higher dose. Sufficient numbers of male and female animals of both species were at risk for the development of late-appearing tumors. In both male and female rats, the incidences of cortical adenomas or carcinomas of the adrenal showed dose-related trends (P<0.001) using pooled controls and, in direct comparisons, were higher in the high-dose groups (P<0.001) than in the pooled controls (males: pooled controls 3/80, matched controls 0/9, low-dose 7/49, high-dose 11/46; females: pooled controls 4/78, matched controls 1/10, low-dose 6/47, high-dose 13/42). Most of the tumors were adenomas. When the matched controls were used, dose-related trends in incidences of the adrenal tumors were significant (males, P=0.048; females, P=0.028); in direct comparisons, however, the incidences of the tumors in the individual groups did not differ significantly from those in corresponding matched controls. The incidences of the tumors in the dosed male and female rats were higher than those in corresponding historical controls (males 8/148, females 5/180). In mice, no tumors occurred in either sex at incidences that were significantly higher in the dosed groups than in the corresponding control groups. It is concluded that under the conditions of this bioassay, parathion was not carcinogenic to B6C3F1 mice. In the male and female Osborne-Mendel rats receiving parathion in their diet, there was a higher incidence of cortical tumors of the adrenal than in pooled or historical controls, suggesting that parathion is carcinogenic to this strain of rat.

Journal Article↗

PubMed1979

Bioassay of procarbazine for possible carcinogenicity.

A bioassay of procarbazine for possible carcinogenicity was conducted by administering the test chemical by intraperitoneal injection to Sprague-Dawley rats and B6C3F1 mice. Groups of 34 or 35 males and 35 or 36 females of both species were administered procarbazine at one of two doses, either 15 or 30 mg/kg for rats, and either 6 or 12 mg/kg for mice. Injections were made three times per week for 26 weeks for the rats and 52 weeks for the mice. Following the periods of injection, the dosed animals were observed for a maximum period of 60 weeks for rats and 33 weeks for mice, depending on survival. Vehicle controls, used for statistical evaluation, consisted of 10 rats and 15 mice of each sex, administered saline solution on the same schedule as the test solution; the same numbers of rats and mice served as untreated controls. Pooled controls consisted of the vehicle controls from this bioassay together with the vehicle controls from two other bioassays similarly performed at the same laboratory. The pooled-control groups consisted of 40 rats of each sex and 45 mice of each sex. Surviving rats were killed at 86 weeks and surviving mice were killed at 85 weeks. Mean body weights of low- and high-dose rats and of high-dose female mice were lower than those of the vehicle controls. Survival rates of both rats and mice showed significant dose-related trends. In rats, malignant lymphomas, adenocarcinomas of the mammary gland, and the combination of olfactory neuroblastomas, adenocarcinomas, or carcinomas of the brain, olfactory bulb, or cerebrum were induced in statistically significant numbers. In mice, malignant lymphomas or leukemias, olfactory neuroblastomas or undifferentiated carcinomas, alveolar/bronchiolar adenomas, and adenocarcinomas of the uterus were induced in statistically significant numbers. It is concluded that under the conditions of this bioassay, procarbazine was carcinogenic for both Sprague-Dawley rats and B6C3F1 mice, producing several types of tumors in both of these two species.

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PubMed1979

Bioassay of phosphamidon for possible carcinogenicity.

A bioassay of technical-grade phosphamidon for possible carcinogenicity was conducted using Osborne-Mendel rats and B6C3F1 mice. The test material was administered in feed to 50 rats and 50 mice of each sex at one of two doses, either 80 or 160 ppm. The rats were fed the test chemical for 80 weeks, then observed without compound administration for 30 or 31 weeks; the low-dose male mice were fed for 71 weeks, then observed for 19 weeks; the high-dose male mice were fed for 62 weeks, then observed for 28 weeks; and the low- and high-dose female mice were fed for 80 weeks, then observed for 10 or 11 weeks. Matched controls consisted of groups of 10 untreated rats or 10 untreated mice of each sex; pooled controls consisted of the matched controls combined with 85 male and 85 female untreated rats or 80 male and 80 female untreated mice from similar bioassays of eight other test chemicals. All surviving rats were killed at 110 or 111 weeks; all surviving mice were killed at 90 or 91 weeks. Hyperexcitability and tremors, both indications of phosphamidon toxicity, were observed in dosed rats and mice. However, sufficient numbers of all groups of both species were at risk for the development of late-appearing tumors. In male rats, the combined incidence of hemangiomas and hemangiosarcomas in the spleen showed a statistically significant (P=0.012) dose-related trend. However, the comparison with matched controls was not significant, and the historical records of this laboratory on untreated males of this strain show a tumor incidence of 6/240 (3%) with incidences in individual control groups as high as 3/9 (33%)and 2/9 (22%), compared with 5/49 (10%) seen in the high-dose group in this study. No hemangiomas or hemangiosarcomas were found in the females. In female rats, the Cochran-Armitage test for dose-related trend was significant (P=0.003) for C-cell adenomas and carcinomas of the thyroid when pooled controls were compared with the dosed groups. The incidences of these tumors were also significant when low-dose females (P=0.003) and high-dose females (P=0.004) were compared directly with pooled controls. However, the historical records of this laboratory show a tumor incidence of 16/235 (7%) in untreated female rats of this strain of female rats, with incidences in individual control groups as high as 3/9 (33%) and 3/10 (30%); these data are therefore considered marginal and insufficient to establish an association between the tumors and administration of the chemical. In males, the incidence of these tumors was not statistically significant. In mice, no tumor occurred at a higher incidence in dosed animals than in controls. It is concluded that under the conditions of this bioassay, technical-grade phosphamidon was not carcinogenic for B6C3F1 mice. The data obtained in this bioassay with Osborne-Mendel rats are insufficient to allow the interpretation that technical-grade phosphamidon is carcinogenic in this species.

Journal Article↗

PubMed1979

Bioassay of Endrin for Possible Carcinogenicity (CAS No. 72-20-8).

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 the adrenal occurred at the following incidences -- males: pooled controls 2/44, matched controls 2/9, low-dose 4/46, high-dose 8/44; females: pooled controls 4/46, matched controls 3/9, low-dose 16/49, high-dose 7/47. These incidences did not show consistent statistical significance. Furthermore, the incidences of the tumors in the matched controls of either sex were higher than those of the corresponding pooled controls, and the incidences in the matched controls equaled or exceeded those in any of the respective dosed groups. Thus, these tumors cannot be clearly related to administration of the test chemical. In mice, no tumors occurred in dosed groups at incidences that were significantly higher than those in pooled or matched controls. It is concluded that under the conditions of this bioassay, endrin was not carcinogenic for Osborne-Mendel rats or for B6C3F1 mice.

Journal Article↗

PubMed1979

Bioassay of toxaphene for possible carcinogenicity.

A bioassay of technical-grade toxaphene 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 toxaphene at one of two doses for 80 weeks, then observed for 28 or 30 weeks. Time-weighted average doses for males were 556 or 1,112 ppm; for females they were 540 or 1,080 ppm. Matched controls consisted of groups of 10 untreated rats of each sex; pooled controls consisted of the matched-control groups for toxaphene combined with 45 untreated male and 45 untreated female rats from similar bioassays of five other test chemicals. All surviving rats were killed at 108-110 weeks. Groups of 50 mice of each sex were administered toxaphene at one of two doses for 80 weeks, then observed for 10 or 11 weeks. Time-weighted average doses were 99 or 198 ppm for both males and females. Matched controls consisted of groups of 10 untreated mice of each sex; pooled controls consisted of the matched-control groups for toxaphene combined with 40 untreated male and 40 untreated female mice from similar bioassays of four other test chemicals. All surviving mice were killed at 90-91 weeks. Mean body weights attained by low- and high-dose female rats and high-dose male mice were lower than those of matched controls, but weights of other dosed groups were essentially unaffected by the toxaphene. Other clinical signs of toxicity in rats included generalized body tremors at week 53 in high-dose male and female animals, and later, leg paralysis, ataxia, epistaxis, hematuria, and vaginal bleeding, predominantly in the dosed groups of rats of each sex. Abdominal distention, diarrhea, dyspnea, and rough hair coats were common to both dosed rats and dosed mice. There were dose-related decreases in survival rates in mice but not in rats. Sufficient numbers of both rats and mice were at risk for the development of late-appearing tumors. In the male rats, the incidence of follicular-cell carcinomas or adenomas of the thyroid was dose related (P=0.007) using the pooled controls (matched controls 1/7, pooled controls 2/44, low-dose 7/41, high-dose 9/35). In the females, the incidence of follicular-cell adenomas of the thyroid was dose related using either the matched (P=0.022) or pooled (P=0.008) controls (matched controls 0/6, pooled controls 1/46, low-dose 1/43, high-dose 7/42). Direct comparisons of dosed and pooled-control groups but not matched controls showed significantly increased incidences of follicular-cell carcinomas or adenomas in the high-dose males (P=0.008) and of follicular-cell adenomas in the high-dose females (P=0.021). Two follicular-cell tumors in the high-dose males were carcinomas; all other follicular-cell tumors in the rats were adenomas. In the mice, the incidence of hepatocellular carcinomas was dose related (P<0.001) for both males (matched controls 0/10, pooled controls 4/48, low-dose 34/49, high-dose 45/46) and females (matched controls 0/9, pooled controls 0/48, low-dose 5/49, high-dose 34/49), using either matched or pooled controls. Direct comparisons showed that the incidences of hepatocellular carcinomas in low- and high-dose male mice and high-dose female mice were all significantly higher (P<0.001) than those in the respective matched or pooled controls. Statistical significance was maintained when the incidence of hepatocellular carcinomas was combined with that of neoplastic nodules of the liver. It is concluded that under the conditions of this bioassay, toxaphene was carcinogenic in male and female B6C3F1 mice, causing increased incidences of hepatocellular carcinomas. The test results also suggest carcinogenicity of toxaphene for the thyroid of male and female Osborne-Mendel rats.

Journal Article↗

PubMed1978

Bioassay of anilazine for possible carcinogenicity (CAS No. 101-05-3).

A bioassay of anilazine for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were administered anilazine at one of two doses, either 500 or 1,000 ppm, for 103 weeks and then observed for 1-6 additional weeks. Matched controls consisted of 25 untreated rats and 25 untreated mice of each sex. All surviving rats were killed at 103-104 weeks; all surviving mice were killed at 107-109 weeks. Administration of the anilazine had no appreciable effect on body weight in the rats and female mice; however, there was a decreased gain in mean body weight in the dosed male mice. Survival also was essentially unaffected. Survival in all groups of dosed and control rats and mice was at least 80% at the end of 90 weeks on study, except for the male control mice; thus, sufficient numbers of animals were at risk in most groups for development of late-appearing tumors. No tumors occurred in dosed rats or mice of either sex at incidences that were significantly higher than those in corresponding controls. Male and female rats and female mice may have been able to tolerate higher doses. It is concluded that under the conditions of this bioassay, anilazine was not carcinogenic for either Fischer 344 rats or B6C3F1 mice.

Journal Article↗

PubMed1978

Bioassay of triphenyltin hydroxide for possible carcinogenicity.

A bioassay of triphenyltin hydroxide for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. Triphenyltin hydroxide was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. The high and low concentrations of triphenyltin hydroxide were, respectively, 75 and 37.5 ppm for rats and mice. After a 78-week period of compound administration, there was an additional observation period of 26 weeks for both species. Twenty animals of each sex and species were placed on test as controls. For male mice, there was a significant positive association between dosage and mortality. In both species, however, adequate numbers of animals survived sufficiently long to be at risk from late-developing tumors. Except for a slight depression of mean body weight gain in male rats and female mice, compound-related mean body weight depression was not observed in either species. In female rats no significant accelerated mortality, retardation of growth, or other signs of toxicity were associated with the dietary administration of triphenyltin hydroxide. Therefore, it is possible that the compound was not administered at the maximum tolerated concentrations. No tumors occurred at a significantly higher incidence in dosed rats or mice than in controls. Under the conditions of this bioassay, there was no evidence for the carcinogenicity of triphenyltin hydroxide to Fischer 344 rats or B6C3F1 mice.

Journal Article↗

PubMed1978

Bioassays of DDT, TDE, and p,p'-DDE for possible carcinogenicity.

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.

Journal Article↗

PubMed1978

Bioassay of aniline hydrochloride for possible carcinogenicity.

A bioassay of aniline hydrochloride for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. Aniline hydrochloride was administered in the feed, at either of two concentrations, to groups of 50 male and female animals of each species, with the exception of 49 female mice in the high dose group. The high and low dietary concentrations of aniline hydrochloride were, respectively, 0.6 and 0.3 percent for rats and 1.2 and 0.6 percent for mice. After a 103-week period of compound administration, observation of the rats and mice continued for up to an additional 5 weeks. For rats and mice, respectively, 25 and 50 animals of each sex were placed on test as controls and fed only the basal diet. In male rats there were several types of mesenchymal tumors, primarily of the spleen, associated with administration of the compound. Hemangiosarcomas of the spleen and the combined incidence of fibrosarcomas and sarcomas NOS of the spleen were each statistically significant in male rats. The combined incidence of fibrosarcomas and sarcomas NOS of multiple body organs was also significant in male rats. The number of female rats having fibrosarcomas or sarcomas NOS of either the spleen alone or multiple organs of the body cavity was significantly associated with increased dietary concentration of aniline hydrochloride. This result was not supported by the Fischer exact tests, but because of the rarity of these tumors, the observed incidences (0/24 in the control group, 1/50 [2 percent] in the low dose group, 7/50 [14 percent] in the high dose group) were considered indicative of a compound-related carcinogenic effect. In mice of both sexes no tumors occurred in statistically significant increased incidences among dosed groups when compared to controls. Under the conditions of this bioassay, dietary administration of aniline hydrochloride was carcinogenic to male and female Fischer 344 rats, inducing hemangiosarcomas and a combination of fibrosarcomas and sarcomas NOS of the spleen and a combination of fibrosarcomas and sarcomas NOS of multiple body organs. There was no evidence of compound-induced carcinogenicity in B6C3F1 mice of either sex.

Journal Article↗

PubMed1978

Bioassay of 5-nitro-o-anisidine for possible carcinogenicity.

A bioassay of 5-nitro-o-anisidine for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 5-Nitro-o-anisidine was administered in the feed at either of two concentrations, to groups of 50 male and 50 female animals of each species. The dietary concentrations used in the chronic bioassay for low and high dose rats were 0.4 and 0.8 percent, respectively. Dose A and B mice were fed dietary concentrations of 0.8 and 1.6 percent when initially placed on test, but after week 15 the concentration fed to dose B mice was reduced to 0.4 percent. After a 78-week period of chemical administration, observation of rats continued for up to an additional 28 weeks and observation of mice continued for up to an additional 19 weeks. For each species, 50 animals of each sex were placed on test as controls for the group receiving the higher concentration and 49 to 50 animals were of each sex were placed on test as controls for the group receiving the lower concentration. In both species, adequate numbers of animals in all groups survived long enough to be at risk from late-developing tumors. Feeding of 5-nitro-o-anisidine to rats was associated with increased incidences of tumors of the integumentary system. Basal-cell carcinomas, trichoepitheliomas, squamous-cell carcinomas and sebaceous adenocarcinomas each occurred in the skin of high dose male rats at statistically significant incidences. For both male and female rats, carcinomas (the combined incidence of sebaceous adenocarcinomas, ceruminous carcinomas and squamous-cell carcinomas) of the Zymbal's gland or the skin of the ear were significant in the high dose groups. In the clitoral gland of dosed female rats, the incidence of carcinomas and the incidence of adenomas were each significant. Among mice, the incidence of hepatocellular carcinoma was statistically significant for dose B females when compared to their appropriate controls. Under the conditions of this bioassay, dietary administration of 5-nitro-o-anisidine was carcinogenic in Fischer 344 rats, causing tumors of the integumentary system in males and females and of the clitoral gland in females. The compound was also carcinogenic to female B6C3F1 mice, causing hepatocellular carcinomas.

Journal Article↗