The fate of N-nitrosodiethanolamine after oral and topical administration to rats

Lethco, E. J.; Wallace, Wendell C.; Brouwer, Emilio A.

doi:10.1016/s0278-6915(82)80104-x

Cited by 22 publications

(8 citation statements)

References 9 publications

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“…Since NDELA has been described to be excreted mainly in its unchanged form in the urine of rats after oral, intravenous, epicutaneous or intratracheal administration [1,11,13,20,21,23], but also after endogenous formation from its potential precursors [20], its excretion in the urine of workers can be considered as an indicator of overall exposure and could be used to justify banning highly nitrosamine-contaminated¯uids.…”

Section: Introductionmentioning

confidence: 99%

Determination of N -nitrosodiethanolamine in urine by gas chromatography thermal energy analysis: application in workers exposed to aqueous metalworking fluids

Ducos¹,

Gaudin²,

Francin³

1999

International Archives of Occupational and Environmental Health

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Section: Introductionmentioning

confidence: 99%

Determination of N -nitrosodiethanolamine in urine by gas chromatography thermal energy analysis: application in workers exposed to aqueous metalworking fluids

Ducos¹,

Gaudin²,

Francin³

1999

International Archives of Occupational and Environmental Health

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“…Careful dose−response studies have shown that NDELA is a potent carcinogen in several species of animals ( , ). NDELA has the unusual property, for a nitrosamine, of being excreted unchanged to the extent of 90−60%, even at the lowest doses ( − ). Oral administration of [ 14 C]NDELA to rats showed that only a small fraction of it is converted to CO 2 ().…”

Section: Introductionmentioning

confidence: 99%

Probing the Mechanism of the Carcinogenic Activation of N-Nitrosodiethanolamine with Deuterium Isotope Effects: In Vivo Induction of DNA Single-Strand Breaks and Related in Vitro Assays

Loeppky

Fuchs

Janzowski

et al. 1998

Chem. Res. Toxicol.

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A series of bioassays, including in vivo induction of DNA single-strand breaks (SSB) and cytotoxicity in cytochrome P450 2E1-transfected cells, were utilized with N-nitrosodiethanolamine (NDELA), its deuterated isotopomers (alpha-D4NDELA and beta-D4NDELA), N-nitroso-2-hydroxymorpholine (NHMOR), and two of its deuterated isotopomers (2-D-NHMOR and 5,5-D2-NHMOR) to probe the mechanism of carcinogenic activation of NDELA and the role of its metabolite NHMOR. DNA samples, taken from the livers of male Wistar rats 4 h after the administration of NDELA, exhibited dose-dependent DNA SSB levels over the range of 0.08-0.75 mmol/kg (body weight), with the greatest SSB level at the highest dose. Deuterium isotope effects on DNA SSB levels were inversely dependent on dose: alpha-D4NDELA, 3. 22-1.37; and beta-D4NDELA, 1.38-0.79. At the lowest dose of 0.15 mmol/kg (body weight), 5,5-D2-NHMOR gave an isotope effect for DNA SSB of 2.8 while that for 2-D-NHMOR was 0.7. NDELA and beta-D4NDELA were equally cytotoxic to human P450 2E1-transfected V79 Chinese hamster cells, while alpha-D4NDELA was not. Significant DNA SSB levels were observed in these cells for NDELA and beta-D4NDELA but not for alpha-D4NDELA. A kinetic deuterium isotope effect of 2.6 for Vmax/Km was observed for the horse liver alcohol dehydrogenase-mediated oxidation of beta-D4NDELA to NHMOR, while kH/kD for alpha-D4NDELA was 1.05. These data provide the first definitive evidence for the activation of NDELA by a pathway involving the scission of the alpha-CH bond and are consistent with P450 2E1-mediated alpha-hydroxylation of NDELA producing the corresponding reactive alpha-hydroxynitrosamine.

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“…NDELA is a water-soluble contaminant and previous percutaneous studies have demonstrated that dermal absorption can vary considerably depending on dosing vehicle and topically applied dose (Airoldi et al, 1983;Bronaugh et al, 1981;Franz et al, 1993;Lethco et al, 1982). There are no previous studies to demonstrate whether this or other nitrososamines are penetration enhancers, yet dihydroxy groups are part of its molecular structure and this suggests that it is a potential dermal enhancer.…”

Section: Discussionmentioning

confidence: 99%

NDELA and nickel modulation of triazine disposition in skin

et al. 2005

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Cutting fluids can become contaminated with metals (e.g., nickel, Ni) and nitrosamines (e.g., N-nitrosodiethanolamine, NDELA) and there is concern that these classes of contaminants can modulate dermal disposition and ultimately the toxicity of cutting fluid additives, such as irritant biocides (e.g., triazine). Biocides are added to these formulations to prevent bacterial degradation of commercial cutting fluids. The purpose of this study was to assess the dermal absorption and skin deposition of 14C-triazine when topically applied to porcine skin in an in vitro flow-through diffusion cell system as aqueous soluble oil (mineral oil, MO) or aqueous synthetic (polyethylene glycol, PEG) mixtures. 14C-Triazine mixtures were formulated with NDELA and/or Ni, or with a combination of three additional cutting fluid additives; namely, 5% linear alkylbenzene sulfonate (LAS), 5% triethanolamine (TEA) and 5% sulfurized ricinoleic acid. Neither Ni nor NDELA was absorbed during these 8-h studies. However, 14C-triazine absorption ranged from 2.72 to 3.29% dose in MO and 2.29-2.88% dose in PEG with significantly greater triazine absorption in MO than PEG when all additives and contaminates were present. The difference between these two diluents was most pronounced when NDELA and/or Ni were present in cutting fluids. These contaminants also enhanced triazine deposition on the skin surface and skin tissues especially with PEG-based mixtures. In essence, the dermal disposition of irritant biocides could be dependent on whether the worker is exposed to a soluble oil or synthetic fluid when these contaminants are present. Workers should therefore not only be concerned about dermatotoxicity of these contaminants, but also the modulated dermal disposition of cutting fluid additives when these contaminants are present in cutting fluid formulations.

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The fate of N-nitrosodiethanolamine after oral and topical administration to rats

Cited by 22 publications

References 9 publications

Determination of N -nitrosodiethanolamine in urine by gas chromatography thermal energy analysis: application in workers exposed to aqueous metalworking fluids

Determination of N -nitrosodiethanolamine in urine by gas chromatography thermal energy analysis: application in workers exposed to aqueous metalworking fluids

Probing the Mechanism of the Carcinogenic Activation of N-Nitrosodiethanolamine with Deuterium Isotope Effects: In Vivo Induction of DNA Single-Strand Breaks and Related in Vitro Assays

NDELA and nickel modulation of triazine disposition in skin

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