Dose-response and ultrastructural alterations in dioxane carcinogenesis.

Argus, Mary F.; Sohal, R. S.; Bryant, Georgia M.; Hoch-Ligeti, Cornelia; Arcos, Joseph C.

doi:10.1016/0014-2964(73)90088-1

Cited by 59 publications

(15 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is evidence that long-term oral administration of 1,4-dioxane causes hepatic and nasal cavity tumors in rodents, [8][9][10][11][12] and accordingly the IARC has classified 1,4-dioxane as a group 2B carcino- gen. 6) With regard to a cancer endpoint, a total daily intake (TDI) of 16 µg of 1,4-dioxane/kg body weight/ day has been calculated by applying an uncertainty factor of 1000 that incorporates 100 for inter-and intraspecies variation and 10 for nongenotoxic carcinogenicity to the no observed adverse effect level of 16 µg/kg body weight/day, as found in a longterm study involving drinking water in rats. 14,15) The 0.440 µg intake of 1,4-dioxane we measured in our study corresponds to 0.055% of the calculated TDI (0.440 µg/{16 µg/kg body weight/day × 50 kg}).…”

Section: Risk From 14-dioxane In Foodmentioning

confidence: 99%

“…6) Long-term oral administration of 1,4-dioxane has been shown to cause tumors in the liver and gallbladder in guinea pigs, 7) and in the nasal cavity and liver of rats. [8][9][10][11] 1,4-Dioxane has also demonstrated promoter activity in studies in mice using a two-stage carcinogenic test. 12) Levels of 1,4-dioxane between 0.2 mg/l and 1.5 mg/l were also detected in tap water samples collected during 1995 and 1996 from six cities in Kanagawa prefecture, Japan.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Study of 1,4-Dioxane Intake in the Total Diet Using the Market-Basket Method

Nishimura

Iizuka

Kibune

et al. 2004

JOURNAL OF HEALTH SCIENCE

View full text Add to dashboard Cite

This solution was applied to a pair of active carbon solid-phase cartridges and the analyte was eluted from each cartridge with dichloromethane. The eluted solution was prepared for gas chromatographic/mass spectrometric analysis by reduction to a volume of 1 ml under a gentle stream of nitrogen. The detection limit of the analysis was 2 g/ kg. We found that the 1,4-dioxane content of 12 food groups ranged between 2 g/kg and 15 g/kg. From these results, the total daily intake of 1,4-dioxane was calculated to be 0.440 g. An intake of this magnitude corresponds to 0.055% of the calculated total daily intake (TDI) (16 g/kg body weight/day). This study indicates that the amount of 1,4-dioxane intake contributed by food is very low and that this value does not represent a potential problem as it does not raise the risk of carcinogenesis.

show abstract

Section: Risk From 14-dioxane In Foodmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Study of 1,4-Dioxane Intake in the Total Diet Using the Market-Basket Method

Nishimura

Iizuka

Kibune

et al. 2004

JOURNAL OF HEALTH SCIENCE

View full text Add to dashboard Cite

show abstract

“…6) With regard to a cancer endpoints, a TDI of 16 µg of 1,4-dioxane/kg body weight/day has been calculated by applying an uncertainty factor of 1000 to the level of 16 µg/kg body weight/day at which no adverse effects were observed in a longterm study of drinking water in rats. 15,16) This uncertainty factor incorporates 100 for inter-and intraspecies variation and 10 for nongenotoxic carcinogenicity.…”

Section: Content Of 14-dioxane In the Mixed Meal Samplesmentioning

confidence: 99%

“…[5][6][7][8] Studies in mice using a two-stage carcinogenic test have demonstrated 1,4-dioxane also has promoter activity. 9) In 2003, 1,4-dioxane was added to the revised water quality standards in Japan.…”

Section: Introductionmentioning

confidence: 99%

Study of 1,4-Dioxane Intake in the Total Diet

Nishimura

Iizuka

Kibune

et al. 2005

JOURNAL OF HEALTH SCIENCE

View full text Add to dashboard Cite

1,4-Dioxane is a newly added compound to the water quality standards in Japan that were revised in 2003. In order to estimate the contribution of 1,4-dioxane in drinking water to the total exposure in humans, it is necessary to take into account the quantity of the compound in food. In an earlier study, we measured the intake of 1,4-dioxane in food based on the average consumption of food in the Kanto area.1) The total daily intake of 1,4-dioxane was calculated to be 0.440 g. In the present study, we investigated the intake of 1,4-dioxane from food by sampling meals from 3 days from 3 homes in 9 prefectures, respectively. 1,4-Dioxane was extracted from 20 g of homogenates of mixed meals using the steam distillation, concentrated by a solid phase cartridge and then measured using gas-chromatography/mass spectrometry. The detection limit of the analysis was 2 g/kg. No 1,4-dioxane was detected in 26 samples, while 3 g/kg was detected in one sample. In this sample case, the daily intake of the 1,4-dioxane was calculated as 4.5 g that represented 0.56% of the total daily intake (TDI) (4.5 g/{16 g/ kg body weight/day ؋ 50 kg}).

show abstract

“…Aside from inducing hepatic and renal effects it has also been shown to induce liver tumors in rodents and to induce nasal carcinomas in rats (42)(43)(44). Young et al (45) showed that the metabolism of 1,4-dioxane was saturable at high doses.…”

Section: Ethylene Oxidementioning

confidence: 99%

Applications of physiologic pharmacokinetic modeling in carcinogenic risk assessment.

Krewski

Withey

et al. 1994

Environ Health Perspect

View full text Add to dashboard Cite

The use of physiologically based pharmacokinetic (PBPK) models has been proposed as a means of estimating the dose of the reactive metabolites of carcinogenic xenobiotics reaching target tissues, thereby affording an opportunity to base estimates of potential cancer risk on tissue dose rather than external levels of exposure. In this article, we demonstrate how a PBPK model can be constructed by specifying mass-balance equations for each physiological compartment included in the model. In general, this leads to a system of nonlinear partial differential equations with which to characterize the compartmental system. These equations then can be solved numerically to determine the concentration of metabolites in each compartment as functions of time. In the special case of a linear pharmacokinetic system, we present simple closed-form expressions for the area under the concentration-time curves (AUC) in individual tissue compartments. A general relationship between the AUC in blood and other tissue compartments is also established. These results are of use in identifying those parameters in the models that characterize the integrated tissue dose, and which should therefore be the primary focus of sensitivity analyses. Applications of PBPK modeling for purposes of tissue dosimetry are reviewed, including models developed for methylene chloride, ethylene oxide, 1,4-dioxane, 1-nitropyrene, as well as polychlorinated biphenyls, dioxins, and furans. Special considerations in PBPK modeling related to aging, topical absorption, pregnancy, and mixed exposures are discussed. The linkage between pharmacokinetic models used for tissue dosimetry and pharmacodynamic models for neoplastic transformation of stem cells in the target tissue is explored. Environ Health Perspect 1 02(Suppl 1 1): 37-50 (1994)

show abstract

Dose-response and ultrastructural alterations in dioxane carcinogenesis.

Cited by 59 publications

References 16 publications

Study of 1,4-Dioxane Intake in the Total Diet Using the Market-Basket Method

Study of 1,4-Dioxane Intake in the Total Diet Using the Market-Basket Method

Study of 1,4-Dioxane Intake in the Total Diet

Applications of physiologic pharmacokinetic modeling in carcinogenic risk assessment.

Contact Info

Product

Resources

About