National Toxicology Program Technical Report Series

Our medical research library holds 5 studies published in National Toxicology Program Technical Report Series (1983–1990). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 5 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Environmental Health Information Service
• Published: 1982 to the present, United States
• Language: English
• ISSN: 0888-8051 (print)
• Continues: National Cancer Institute Carcinogenesis Technical Report Series
• Its record in the NLM Catalog

1990s

• NTP Lifetime Carcinogenesis Studies of Chrysotile Asbestos (CAS No. 12001-29-5) in Syrian Golden Hamsters (Feed Studies). National Toxicology Program. 1990;246:1-192. PubMed

  Abstract

  NTP Carcinogenesis studies of short range (SR), intermediate range (IR), or intermediate range chrysotile asbestos in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted with male and female Syrian golden hamsters. Both forms of chrysotile asbestos were administered at the concentration of 1% in pelleted diet for the entire lifetime of the hamsters starting with mothers of the test animals. Group sizes varied from 125 to 253. Starting at 6 weeks of age, male and female hamsters in the intermediate range chrysotile/DMH study were given oral doses of DMH (4 mg/kg) every other week for a total of 5 doses. There was no adverse effect on body weight gain or survival by either form of asbestos or by asbestos in combination with DMH. A significant increase (P< 0.05) in adrenal cortical adenomas was observed in male hamsters exposed to SR and IR chrysotile asbestos and in females treated with IR chrysotile asbestos when compared to the pooled control groups (males: pooled controls, 25/466, 5%; SR chrysotile, 26/299, 11%; IR chrysotile, 24/244, 10%; females: pooled controls, 15/468, 3%; IR chrysotile, 18/234, 8%). However, statistical significance was lost when these dosed groups were compared with concurrent control groups (males: SR control, 7/115, 6%; IR control, 7/115, 6%; females: SR control, 4/112, 4%; IR control, 6/118, 5%). The results of the combination study (IR chrysotile plus DMH) did not yield a significant increase in tumors above the background level observed in the DMH group alone or in the untreated control group. The DMH failed to yield a background level of intestinal tumors high enough to provide a valid test of the cocarcinogenic potential of chrysotile asbestos. For this reason, the cocarcinogenic potential of orally administered asbestos should be considered untested. Under the conditions of these studies, neither short range chrysotile nor intermediate range chrysotile asbestos was carcinogenic when ingested at 1% levels in the diet by male and female Syrian golden hamsters. While there were increases in the rates of adrenal cortical adenomas in male and female hamsters exposed to intermediate range chrysotile asbestos compared to the pooled groups, these incidence rates were not different when compared with the concurrent control groups. Additionally, the biologic importance of adrenal tumors in the absence of target organ (gastrointestinal tract) neoplasia is questionable. The coNTP Carcinogenesis studies using IR chrysotile asbestos and 1,2-dimethylhydrazine dihydrochloride were considered inadequate because there was no increase in intestinal neoplasia in the DMH group. Levels of Evidence of Carcinogenicity: Intermediate Range: Male Hamsters: Negative Female Hamsters: Negative Intermediate Range + dimethyl hydrazine: Male Hamsters: Inadequate Female Hamsters: Inadequate Short Range: Male Hamsters: Negative Female Hamsters: Negative.

• NTP Toxicology and Carcinogenesis Studies of Amosite Asbestos (CAS No. 12172-73-5) in F344/N Rats (Feed Studies). National Toxicology Program. 1990;279:1-341. PubMed

  Abstract

  The term "asbestos" has a commercial/industrial derivation limited to naturally occurring fibrous minerals of the serpentine or amphibole series. Chrysotile is the only type of asbestos in the serpentine series, whereas the amphibole series is represented by actinolite, amosite, anthophyllite, crocidolite, and tremolite. The essential characteristic of asbestos minerals is their fibrous nature. Large portions of the population ingest asbestos through consumption of food and water. Asbestos or asbestos-like fibers may gain access to water supplies as a result of mining (Lake Superior), from the presence of natural serpentine or amphibole deposits in watersheds (Seattle, WA, and San Francisco, CA) or, under certain conditions, through the use of asbestos-cement pipes for municipal water supplies. For the latter, erosion of the pipe with release of fibers is associated with the "aggressiveness" of the water, a term representing a mathematical expression of pH, alkalinity, and calcium content. The EPA estimated that 68.5% of water systems in the United States utilize water that is potentially capable of eroding asbestos-cement pipe. Carcinogenesis studies of amosite asbestos alone or in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted in male and female rats. Amosite asbestos was administered at a concentration of 1% in pelleted diet for the entire lifetime of the rats, starting with the dams of the study animals. One group of amosite asbestos-exposed rats (amosite preweaning gavage) also received chrysotile asbestos via gavage during lactation. Group sizes varied from 100 to 250. Litter size was the same, but the offspring from mothers exposed to amosite asbestos were smaller at weaning than those from nonexposed mothers and remained smaller throughout their life. The DMH was administered by gavage at a dose of 7.5 mg/kg for males and 15 mg/kg for females every 14 days, starting at 8 weeks of age, for a total of five doses. The administration of DMH did not affect body weight gain either in amosite-exposed or nonexposed animals. The amosite-exposed rats showed enhanced survival compared with that of the nonexposed rats. DMH exposure reduced survival by approximately 1 year, although the survival of the amosite plus DMH groups was slightly greater than that of the DMH group alone. Significant increases in the incidences of C-cell carcinomas of the thyroid gland (untreated control, 11/117; amosite, 50/246, P<0.05; amosite preweaning gavage, 14/100) and of leukemia (38/117; 106/249, P<0.05; 49/100, P<0.01) in male rats were observed in amosite-exposed groups. However, the biologic significance of the C-cell carcinomas in relation to amosite asbestos exposure is discounted because of a lack of significance when C-cell adenomas and carcinomas were combined and because the positive effect was not observed in the amosite preweaning gavage group. The biologic significance of an increased incidence of leukemia is questionable because of a lack of statistical significance in the amosite group when evaluated by life table analysis and because no toxic lesions were observed in the target organs, i.e., gastrointestinal tract and mesothelium. DMH caused a high incidence (62%-74%) of intestinal neoplasia in amosite-exposed and nonexposed groups. Neither an enhanced carcinogenic nor a protective effect was demonstrated by exposure to amosite asbestos. Conclusions: Under the conditions of these feed studies, amosite asbestos was not overtly toxic, did not affect survival, and was not carcinogenic when ingested at a concentration of 1% in the diet by male or female F344/N rats. The cocarcinogenic studies using DMH were considered inadequate because of the high incidence of DMH-induced intestinal neoplasia in both the amosite asbestos-exposed and nonexposed groups. Levels of Evidence of Carcinogenicity: Amosite Asbestos: Male Rats: Negative. Female Rats: Negative. Amosite Asbestos + DMH: Male Rats: Inadequate. Female Rats: Inadequate. Note: Amosite Asbestos was previously tested in Syrmosite Asbestos was previously tested in Syrian Golden Hamsters administered in feed (See TR-249, reported 1983).

1980s

• NTP Toxicology and Carcinogenesis Studies of Crocidolite Asbestos (CAS No. 12001-28-4) In F344/N Rats (Feed Studies). National Toxicology Program. 1988;280:1-178. PubMed

  Abstract

  Carcinogenesis studies of crocidolite asbestos were conducted with male and female F344/N rats. This form of asbestos was administered at a concentration of 1% in pelleted diet for the lifetime of the rats, starting with the dams of the study animals. The studies were started in January 1978 and ended in December 1980. Group sizes were 118 for male and female controls and 250 for male and female crocidolite asbestos-exposed rats. The offspring from mothers exposed to crocidolite asbestos and the controls were similar in size at birth but were slightly smaller at weaning and remained so throughout their life. Feed consumption and survival were comparable in the exposed and control groups. No overt toxicity was observed in the crocidolite asbestos-exposed animals. There was an elevated (P<0.05) incidence of thyroid gland C-cell adenomas (control, 4/117, 3%, vs. exposed, 23/250, 9%) and of thyroid gland C-cell carcinomas (12/117, 10%, vs. 46/250, 18%) in crocidolite asbestos-exposed female rats relative to concurrent controls. Because these control incidences were low relative to control incidences observed in other contemporary studies at this laboratory (21% for thyroid gland C-cell tumors), this slight increase was not regarded as being biologically important. The data, documents, and pathology materials from the lifetime studies of crocidolite asbestos have been audited. The audit findings show that the conduct of these studies is documented adequately and support the data and results presented in this Technical Report. Conclusions: Under the conditions of these feed studies, crocidolite asbestos was not overtly toxic and did not cause a carcinogenic response when ingested at a concentration of 1% in the diet by male and female F344/N rats for their lifetime. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative

• NTP Toxicology and Carcinogenesis Studies of Chrysotile Asbestos (CAS No. 12001-29-5) in F344/N Rats (Feed Studies). National Toxicology Program. 1985;295:1-390. PubMed

  Abstract

  Lifetime toxicology and carcinogenesis studies of short-range (SR) and intermediate-range (IR) fiber length chrysotile asbestos were conducted in groups of 88-250 male and female F344/N rats. Both forms of asbestos were administered at a concentration of 1% in pelleted diet for the lifetime of the rats, starting with the dams of the test animals. Subgroups of 100 male and female IR chrysotile-exposed rats also received 0.47 mg/g IR chrysotile asbestos in water by gavage during lactation (preweaning [PW]). At 9 weeks of age, additional subgroups (125-175) of control and IR chrysotile-exposed rats received 7.5 mg/kg (male) or 15 mg/kg (female) 1,2-dimethylhydrazine dihydrochloride (DMH) by gavage every other week for a total of five doses. When the survival of either the control or test group reached 10%, both groups were killed. Neither type of fiber affected fertility or litter size. The offspring from mothers exposed to SR chrysotile were similar in body weight to the controls at birth but were slightly smaller (13%) at weaning and remained so throughout their lifetimes. Feed consumption and survival were comparable among the SR and IR chrysotile asbestos groups and controls. The DMH-exposed groups showed decreased survival due primarily to the development of lethal neoplasms. The administration of SR chrysotile for the lifetime of exposed male and female rats did not cause any overt toxicity. In addition, no neoplastic or nonneoplastic disease was associated with SR chrysotile exposure. Male and female rats exposed to IR chrysotile asbestos did not show any adverse clinical signs. Benign epithelial neoplasms (adenomatous polyps) were observed in the large intestine of IR chrysotile asbestos male rats (9/250, 3.6%). Although not statistically significant (P=0.08) compared with concurrent controls (0/85), the incidence of these neoplasms was highly significant (P=0.003) when compared with the incidence of epithelial neoplasms (benign and malignant combined) of the large intestine in the pooled male control groups of all the NTP oral asbestos lifetime studies (3/524, 0.6%). The biologic importance of this finding was supported by the observation of lesions of similar morphology in the small intestine or glandular stomach of four additional IR chrysotile male rats and by a low incidence (2/100, 2.0%) of adenomatous polyps in the large intestine of male rats in the IR/PW group. A significant (P<0.05) increase in keratoacanthomas of the skin was observed in male IR (19/250, 7.6%) and IR/PW (8/100, 8.0%) chrysotile-exposed rats compared with the concurrent controls (1/88, 1.1%). The biologic importance of this observation was discounted because the incidence in these groups did not greatly exceed the rate observed in the combined male control groups from all the other NTP oral asbestos studies (19/441, 4.3%). An apparent increase in the incidence of clitoral gland neoplasms in female IR (18/250, 7.2%) and IR/PW (4/100, 4.0%) chrysotile-exposed rats compared with that in the concurrent controls (1/88, 1.1%) was also discounted because of a lack of statistical significance when compared with the pooled female control groups from the other NTP oral asbestos studies (21/441, 4.8%). Rats exposed to DMH and DMH plus IR chrysotile asbestos exhibited neoplasia in those organs known to be targets for DMH (gastrointestinal tract, Zymbal gland, liver, and kidney). There was a significant difference (P<0.05) in the incidence of DMH-induced mixed-cell tumors of the kidney between the DMH alone (13/125, 10%) and DMH plus IR chrysotile asbestos (34/175, 19%) female groups. An increased incidence of thyroid follicular cell tumors was observed in DMH plus IR chrysotile male rats (28/175, 16.0%) compared with the DMH alone group (9/124, 7.3%). The biologic importance of both observations is questionable, since neither organ represents a primary target organ for asbestos and no difference between DMH and DMH plus IR chrysotile was observed for the primary target organs (intestine and mesothelium). An audit of the experimental data was conducteIR chrysotile was observed for the primary target organs (intestine and mesothelium). An audit of the experimental data was conducted for these lifetime carcinogenesis studies of chrysotile asbestos. No data discrepancies were found that influenced the final interpretations. Under the conditions of these lifetime studies, short-range and intermediate-range chrysotile asbestos did not induce overt toxicity and did not affect survival when ingested at a level of 1% in the diet by male and female F344/N rats. There was no evidence of carcinogenicity in male or female rats exposed to SR chrysotile asbestos or in female rats exposed to IR chrysotile asbestos. There was some evidence of carcinogenicity in male rats exposed to IR chrysotile asbestos as indicated by an increased incidence of adenomatous polyps in the large intestine. The cocarcinogenesis studies of 1,2-dimethylhydrazine dihydrochloride and IR chrysotile asbestos were considered inconclusive for determining whether IR chrysotile asbestos had either a tumor-enhancing or protective effect, although an increased incidence of neoplasms was observed in the kidneys of female rats exposed to DMH plus IR chrysotile as compared with those exposed to DMH alone.

• NTP Lifetime Carcinogenesis Studies of Amosite Asbestos (CAS No. 12172-73-5) in Syrian Golden Hamsters (Feed Studies). National Toxicology Program. 1983;249:1-81. PubMed

  Abstract

  Carcinogenesis studies of amosite asbestos were conducted by administering diets containing 1% of the asbestos in pellets from the conception of the mothers through the lifetime of male and female Syrian golden hamsters. Control groups consisted of 127 male and 126 female hamsters and the amosite asbestos groups consisted of 252 male and 254 female hamsters. No adverse effect on body weight gain or survival was observed from treatment with amosite asbestos. Neither of the amosite asbestos groups showed increased neoplasia in any organ or tissue compared to the control groups. Under the conditions of these studies, the ingestion of amosite asbestos at a level of 1% in the diet for their lifetime was not toxic and did not cause a carcinogenic response in male and female Syrian golden hamsters. Levels of Evidence of Carcinogenicity: Male Hamsters: Negative Female Hamsters: Negative

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