Stimulation of DNA Synthesis in Mouse and Rat Lung Following Administration of Butylated Hydroxytoluene

Larsen, John Christian; Tarding, F.

doi:10.1007/978-3-642-66896-8_18

Cited by 16 publications

(3 citation statements)

References 5 publications

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“…All mouse strains examined so far are susceptible to BHT (64,98,102). Other laboratory rodents, however, particularly rats, hamsters and rabbits, do not develop lung damage after BHT (63,98,104).…”

Section: Interactions Resulting From Exposures Separated In Timementioning

confidence: 99%

“…Lung damage, as measured by increased ventilation rate, was significantly reduced if the priming dose (50 mg/kg) was given either 7 or 14 days before 250 mg/kg of cyclophosphamide. However, if the animals were "primed" on the day prior to the large dose of the drug, lung damage seemed to be enhanced (94 (96) and has since been confirmed in several laboratories (64,(97)(98)(99)(100)(101). Diffuse lung lesions develop after oral or intraperitoneal administration of BHT and are dose-dependent (102,103).…”

Section: Interactions Resulting From Exposures Separated In Timementioning

confidence: 99%

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The role of toxicological interactions in lung injury.

Witschi¹,

Hakkinen²

1984

Environ Health Perspect

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Interactions between two or more toxic agents can produce lung damage by chemical-chemical interactions, chemical-receptor interactions or by modification, by a first agent, of the cell and tissue response to a second agent. Interactions may occur by simultaneous exposure and if exposure to the two agents is separated in time. Chemical-chemical interactions have been mostly studied in the toxicology of air pollutants, where it was shown that the untoward effect of certain oxidants may be enhanced in the presence of other aerosols. Interactions at the receptor site have been found in isolated perfused lung experiments. Oxygen tolerance may be an example, when pre-exposure to one concentration of oxygen mitigates later exposure to 100% oxygen by modifying cellular and enzymatic composition of the lung. Damage of the alveolar zone by the antioxidant butylated hydroxytoluene (BHT) can be greatly enhanced by subsequent exposure to oxygen concentration which, otherwise, would have little if any demonstrable effect. The synergistic interaction between BHT and oxygen results in a resulting interstitial pulmonary fibrosis. Acute or chronic lung disease may then be caused not only by one agent, but very likely in many instances by the interaction of several agents.

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Section: Interactions Resulting From Exposures Separated In Timementioning

confidence: 99%

Section: Interactions Resulting From Exposures Separated In Timementioning

confidence: 99%

The role of toxicological interactions in lung injury.

Witschi¹,

Hakkinen²

1984

Environ Health Perspect

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“…Mitotic gures were rarely observed. Larsen and Tarding (1978) also reported that BHT stimulated DNA synthesis in the lungs of NMRI mice and Wistar rats. A single dose of 500 mg/kg BHT (in soybean oil) was administered IP or by gavage, and [ 14 C]-thymidine was given 4 days later.…”

Section: Effects On Macromoleculesmentioning

confidence: 90%

Final Report on the Safety Assessment of BHT

Lanigan¹,

Yamarik²

2002

Int J Toxicol

147

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BHT is the recognized name in the cosmetics industry for butylated hydroxytoluene. BHT is used in a wide range of cosmetic formulations as an antioxidant at concentrations from 0.0002% to 0.5%. BHT does penetrate the skin, but the relatively low amount absorbed remains primarily in the skin. Oral studies demonstrate that BHT is metabolized. The major metabolites appear as the carboxylic acid of BHT and its glucuronide in urine. At acute doses of 0.5 to 1.0 g/kg, some renal and hepatic damage was seen in male rats. Short-term repeated exposure to comparable doses produced hepatic toxic effects in male and female rats. Subchronic feeding and intraperitoneal studies in rats with BHT at lower doses produced increased liver weight, and decreased activity of several hepatic enzymes. In addition to liver and kidney effects, BHT applied to the skin was associated with toxic effects in lung tissue. BHT was not a reproductive or developmental toxin in animals. BHT has been found to enhance and to inhibit the humoral immune response in animals. BHT itself was not generally considered genotoxic, although it did modify the genotoxicity of other agents. BHT has been associated with hepatocellular and pulmonary adenomas in animals, but was not considered carcinogenic and actually was associated with a decreased incidence of neoplasms. BHT has been shown to have tumor promotion effects, to be anticarcinogenic, and to have no effect on other carcinogenic agents, depending on the target organ, exposure parameters, the carcinogen, and the animal tested. Various mechanism studies suggested that BHT toxicity is related to an electrophillic metabolite. In a predictive clinical test, 100% BHT was a mild irritant and a moderate sensitizer. In provocative skin tests, BHT (in the 1% to 2% concentration range) produced positive reactions in a small number of patients. Clinical testing did not find any depigmentation associated with dermal exposure to BHT, although a few case reports of depigmentation were found. The Cosmetic Ingredient Review Expert Panel recognized that oral exposure to BHT was associated with toxic effects in some studies and was negative in others. BHT applied to the skin, however, appears to remain in the skin or pass through only slowly and does not produce systemic exposures to BHT or its metabolites seen with oral exposures. Although there were only limited studies that evaluated the effect of BHT on the skin, the available studies, along with the case literature, demonstrate no significant irritation, sensitization, or photosensitization. Recognizing the low concentration at which this ingredient is currently used in cosmetic formulations, it was concluded that BHT is safe as used in cosmetic formulations.

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