Mutagenic action of isocyanates used in the production of polyurethanes.

Andersen, Martrethe; Binderup, Mona‐Lise; Kiel, Pauli; Larsen, Henry; Maxild, Jette

doi:10.5271/sjweh.2610

Cited by 71 publications

(19 citation statements)

References 8 publications

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“…Since 4,4'-methylenedianiline has been demonstrated to be mutagenic after metabolic activation (Darby et al, 1978;Anderson et al, 1980), 4,4'-methylenedianiline's thyroid carcinogenic activity may involve a genetic mechanism of action. There is also a potential for nonDownloaded by [Stockholm University Library] at 20:02 12 August 2015 genetic mechanism of carcinogenesis involving thyroid hormone activity or inhibition.…”

Section: Discussionmentioning

confidence: 99%

Carcinogenesis studies of 4,4'‐methylenedianiline dihydrochloride given in drinking water to F344/N rats and B6C3F₁mice

Lamb

Huff

Haseman

et al. 1986

Journal of Toxicology and Environmental Health

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Carcinogenesis studies of 4,4'-methylenedianiline dihydrochloride (98.6% pure) were conducted by administering this chemical in the drinking water of F344/N rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex received drinking water containing 150 or 300 ppm 4,4'-methylenedianiline dihydrochloride (dosage expressed as the free base) for 103 wk. Groups of 50 rats and 50 mice of each sex, given drinking water adjusted with 0.1 N HCl to the pH (3.7) of the 300-ppm formulation, served as controls. Survival was comparable among groups except for male mice receiving the 300-ppm dose of 4,4'-methylenedianiline dihydrochloride; survival in that group was lower than that in controls. Mean body weight was reduced in 300-ppm-dose female rats and 300-ppm-dose male and female mice compared to controls. Water consumption was reduced in a dose-related manner in both sexes of rats. No compound-related clinical effects were observed. Under the conditions of these studies, there was clear evidence of carcinogenicity for F344/N rats and for B6C3F1 mice in that 4,4'-methylenedianiline dihydrochloride caused increased incidences of (1) follicular-cell carcinomas of the thyroid gland (controls, 0/49; low dose, 0/47; high dose, 7/48, 15%; p less than or equal to 0.012) and neoplastic nodules of the liver (controls, 1/50, 2%; low dose, 12/50, 24%; high dose, 25/50, 50%; p less than or equal to 0.001) in male rats, (2) follicular-cell adenomas (controls, 0/47; low dose, 2/47, 4%; high dose, 17/48, 35%; p less than or equal to 0.001) and C-cell adenomas (controls, 0/47; low dose, 3/47, 6%; high dose, 6/48, 13% p less than or equal to 0.029) of the thyroid gland in female rats, (3) follicular-cell adenomas of the thyroid gland (controls, 0/47; low dose, 3/49, 6%; high dose, 16/49, 33%; p less than or equal to 0.001), carcinomas of the liver (controls, 10/49, 20%; low dose, 33/50, 66%; high dose, 29/50, 58%; p less than or equal to 0.001), and pheochromocytomas of the adrenal gland in male mice (controls, 2/48, 4%; low dose, 12/49, 24%; high dose, 14/49, 29%; p less than or equal to 0.001), and (4) follicular-cell adenomas of the thyroid gland (controls, 0/50; low dose, 1/47, 2%; high dose, 13/50, 26%; p less than or equal to 0.001), carcinomas (controls, 1/50, 2%; low dose, 6/50, 12%; high dose, 11/50, 22%; p less than or equal to 0.002) and adenomas (controls, 3/50, 6%; low dose, 9/50, 18%; high dose, 12/50, 24%.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Discussionmentioning

confidence: 99%

Carcinogenesis studies of 4,4'‐methylenedianiline dihydrochloride given in drinking water to F344/N rats and B6C3F₁mice

Lamb

Huff

Haseman

et al. 1986

Journal of Toxicology and Environmental Health

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“…However, the findings [33][34][35][36] , especially using Ames test [33][34]36) , need consideration. While many studies found positive Ames tests with MDI and TDI, these used DMSO (dimethylsulfoxid) or other solvents to disperse the diisocyanates into the medium.…”

Section: Mutagenicitymentioning

confidence: 99%

Review of the occupational exposure to isocyanates: Mechanisms of action

Nakashima

Takeshita

Morimoto

2002

Environ Health Prev Med

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Polyurethanes are useful polymers in a large variety of technical and consumer products that are generally made from diisocyanates and polyols or similar compounds. Toluene diisocyanate (TDI), 4,4'-methylenediphenyl diisocyanate (MDI) and 1,6'-hexamethylene diisocyanate (HDI) are useful for polyurethane products. Isocyanates are reactive chemicals that can be handled without problems in manufacturing or technical environments. In general, consumers may only have contact with these chemicals on rare occasions. The objective of this study was to review the mechanisms of action of inhalation of isocyanates. This paper describes, in summary, the potential occupational exposure to isocyanates, the chemistry and reactivity of isocyanates, the results from genotoxicity studies, investigative toxicity studies, metabolism and results from epidemiology studies on isocyanate-exposed workers. The overall conclusion is that because humans are not exposed to high levels of respiratory isocyanate particles, concerns over the possible development of lung tumors should not be relevant. There are many mechanisms of action induced by isocyanates, but those entities are unclear. This is because these mechanisms act simultaneously and are complex.

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“…We consider it therefore necessary to repeat the basis for our conclusions that "isocyanates must be considered to represent a serious health hazard [p 221]" (2).…”

Section: Authors' Response To Wf Diller's Letter To the Editor -Scandmentioning

confidence: 99%

Authors` response to WF Diller`s Letter to the Editor – Scand J Work Environ Health 1981;7:237–238

Andersen¹,

Binderup²,

Kiel³

et al. 1982

Scand J Work Environ Health

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Mutagenic action of isocyanates used in the production of polyurethanes.

Abstract: The following articles refer to this text: 1982;8(1):0; 1981;7(3):157-240

Cited by 71 publications

References 8 publications

Carcinogenesis studies of 4,4'‐methylenedianiline dihydrochloride given in drinking water to F344/N rats and B6C3F₁mice

Carcinogenesis studies of 4,4'‐methylenedianiline dihydrochloride given in drinking water to F344/N rats and B6C3F₁mice

Review of the occupational exposure to isocyanates: Mechanisms of action

Authors` response to WF Diller`s Letter to the Editor – Scand J Work Environ Health 1981;7:237–238

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Mutagenic action of isocyanates used in the production of polyurethanes.

Abstract: The following articles refer to this text: 1982;8(1):0; 1981;7(3):157-240

Cited by 71 publications

References 8 publications

Carcinogenesis studies of 4,4'‐methylenedianiline dihydrochloride given in drinking water to F344/N rats and B6C3F1mice

Carcinogenesis studies of 4,4'‐methylenedianiline dihydrochloride given in drinking water to F344/N rats and B6C3F1mice

Review of the occupational exposure to isocyanates: Mechanisms of action

Authors` response to WF Diller`s Letter to the Editor – Scand J Work Environ Health 1981;7:237–238

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Product

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Carcinogenesis studies of 4,4'‐methylenedianiline dihydrochloride given in drinking water to F344/N rats and B6C3F₁mice

Carcinogenesis studies of 4,4'‐methylenedianiline dihydrochloride given in drinking water to F344/N rats and B6C3F₁mice