Chronic effects of dietary exposure to amosite asbestos and tremolite in F344 rats

Our plain-English summary of Chronic effects of dietary exposure to amosite asbestos and tremolite in F344 rats, by E.E. McConnell, H.A. Rutter, B.M. Ulland, et al (Environmental Health Perspectives, 1983).

The study

• Authors: E.E. McConnell, H.A. Rutter, B.M. Ulland, J.A. Moore
• Journal: Environmental Health Perspectives
• Published: 1983;53:27-44
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 000624).

Abstract

Carcinogenesis bioassays of blocky (nonfibrous) tremolite and amosite asbestos alone or in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted with male and female Fischer 344 rats. The minerals were administered at a concentration of 1% in pelleted diet for the entire lifetime of the rats starting with the dams of the test animals. One group of amosite rats also received chrysotile asbestos via gavage during lactation. Group sizes varied from 100 to 250 animals. The offspring from mothers exposed to tremolite or amosite asbestos were smaller at weaning than those from untreated mothers and remained smaller throughout their life. The administration of dimethylhydrazine (DMH) did not affect body weight gain, either in amosite-exposed or nonexposed animals. Survival was comparable in the tremolite and control groups. The amosite-exposed rats showed enhanced survival compared to the untreated controls. DMH exposure reduced survival by approximately one year, although the amosite plus DMH groups survived slightly better than the DMH alone groups. No toxicity or increase in neoplasia was observed in the tremolite-exposed rats compared to the controls. Significant increases (p less than 0.05) in the rates of C-cell carcinomas of the thyroid and monocytic (mononuclear cell) leukemia in male rats were observed in amosite-exposed groups. However, the biological 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 the positive effect was not observed in the amosite plus preweaning gavage group. The biological significance of an increased incidence of mononuclear cell leukemia is questionable, because of a lack of statistical significance in the amosite group when evaluated using life table analysis, lack of significance when compared to the tremolite control group, and the fact that no toxic or neoplastic lesions were observed in the target organs, i.e., gastrointestinal tract and mesothelium. DMH caused a high rate of (62-74%) of intestinal neoplasia in amosite and nonamosite-exposed groups. Neither an enhanced carcinogenic nor protective effect was demonstrated by exposure to amosite asbestos.

In plain English

In this lifetime experiment, male and female Fischer 344 rats ate diet containing 1% amosite asbestos or 1% tremolite, starting with their mothers. The tremolite was nonfibrous in its natural form, but a small amount became fibrous during milling. Groups held 100 to 250 rats of each sex. One amosite group was mistakenly given chrysotile by stomach tube before weaning. Some rats also received DMH, a known intestinal carcinogen. Mineral-exposed offspring were smaller at weaning. Survival with tremolite did not differ significantly from controls. Rats fed amosite alone outlived untreated controls, but males also given preweaning chrysotile survived slightly less well. No toxicity or tumor increase was seen with tremolite. Amosite-fed males had more thyroid C-cell carcinomas (50 of 246, versus 11 of 117 controls) and more mononuclear cell leukemia (106 of 249, versus 38 of 117). The authors did not consider the thyroid increase treatment-related and doubted that the leukemia increase was. DMH caused intestinal tumors in 62 to 74% of rats, with or without amosite; the authors considered that part flawed. The authors concluded that 1% tremolite or amosite in the diet was not toxic or carcinogenic.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Lifetime carcinogenesis bioassay in rats (animal experiment). It also tested whether amosite modified the effect of the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH).
• Who was studied: Male and female Fischer 344 rats born to mothers already on the test diets. Group sizes per sex were: control 118, tremolite 250, second control 117, DMH 125, amosite 250, amosite plus DMH 175, and amosite plus preweaning gavage 100. The animal work was done at Hazleton Laboratories America, Vienna, VA. No study dates are given.
• Exposure: Diet containing 1% amosite asbestos (from Penge, Transvaal, South Africa) or 1% tremolite (from the Gouverneur Talc Company, NY) for the entire lifetime, starting with the dams. The tremolite was described as crystalline or nonfibrous in its natural form, with a small amount becoming fibrous during crushing and milling. One amosite group was inadvertently gavaged with medium-range chrysotile, instead of amosite, at 0.47 mg/g body weight from birth to weaning (21 days). From 8 weeks of age, one control group and one amosite group received DMH by gavage every 14 days for five doses (7.5 mg/kg in males, 15.0 mg/kg in females).
• Main results:
  • Offspring of exposed mothers were smaller at weaning: tremolite-exposed 22.8 g versus 26.3 g in controls, and amosite-exposed 23.2 g versus 27.4 g in controls. They remained smaller throughout life.
  • Survival did not differ significantly between the tremolite-exposed and control groups.
  • Rats fed amosite alone survived better than untreated controls. At 106 weeks, 88% of amosite males were alive versus 81% of their untreated control males. The authors suggested this was due to lower body weight.
  • Males fed amosite that had also been given chrysotile by gavage before weaning survived slightly less well than untreated controls.
  • No toxicity or increase in tumors was observed in tremolite-exposed rats compared with controls.
  • In the control and amosite groups without DMH, intestinal tumors were low, with no significant difference between treated and control groups. Non-cancerous gastrointestinal lesions were not increased.
  • Thyroid C-cell carcinoma was significantly increased (p less than 0.05) in amosite-exposed males: 50 of 246 (20%), versus 11 of 117 (9%) in untreated control males. The increase was not seen in amosite plus preweaning gavage males (14 of 100, 14%). Total C-cell tumors (adenomas and carcinomas combined) were comparable between control and treated groups, and the authors did not consider the finding treatment-related.
  • Mononuclear cell leukemia was increased in amosite males, 106 of 249 (42%; p less than 0.05), and in amosite plus preweaning gavage males, 49 of 100 (49%; p less than 0.01), versus 38 of 117 (32%) in untreated control males. Neither increase was significant compared with the tremolite control group (39% in males). The increase was not seen in females. The authors judged a treatment relationship doubtful.
  • DMH caused gastrointestinal tumors in 92 of 125 (74%) males and 77 of 124 (62%) females given DMH alone. The figures were 118 of 173 (68%) males and 114 of 175 (65%) females given amosite plus DMH. The authors described these incidences as essentially comparable.
• The authors' conclusion: The authors concluded that, under the conditions of this lifetime bioassay, tremolite or amosite asbestos at 1% in the diet was not toxic, did not affect survival, and was not carcinogenic in male and female Fischer 344 rats. They considered the biological significance of the increased thyroid C-cell carcinomas and leukemia in amosite-exposed males questionable.
• Limitations the authors state:
  • The authors considered the DMH co-carcinogenesis part of the study flawed because of the high rate of intestinal cancer in both DMH groups. This rate was much higher than the roughly 15% their pilot study predicted.
  • Because of the high background of DMH-induced tumors, the authors could not determine accurately whether amosite had a co-carcinogenic or additive effect.
  • One amosite group was given chrysotile instead of amosite by gavage before weaning. The authors state this group should nonetheless be regarded as exposed to amosite for life.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite, Tremolite.

Medical terms in this study, explained in our Lexicon: Amosite, Tremolite, Carcinogenesis, Chrysotile, Carcinoma, Asbestos Exposure, Statistical Significance, Mesothelium.

Related studies

• Chronic effects of dietary exposure to amosite and chrysotile asbestos in Syrian golden hamsters — E.E. McConnell, A.M. Shefner, et al. (1983)
• Inhalation studies on the effects of tremolite and brucite dust in rats — J.M. Davis, J. Addison, et al. (1985)
• Biological effects of tremolite — J.C. Wagner, M. Chamberlain, et al. (1982)
• Pulmonary changes after exposure to vermiculite contaminated with fibrous tremolite — J.E. Lockey, S.M. Brooks, et al. (1984)
• Cohort study of mortality of vermiculite miners exposed to tremolite — J.C. McDonald, A.D. McDonald, et al. (1986)
• Chrysotile, tremolite, and malignant mesothelioma in man — A. Churg (1988)

Browse more research in Environmental Health Perspectives, or return to medical research.