Percutaneous absorption of co-administered N-methyl-2-[14C]pyrrolidinone and 2-[14C]pyrrolidinone in the rat

Midgley, I.; Hood, Ashley J.; Chasseaud, L. F.; Brindley, Charlie; Baughman, Sharon A.; Allan, Gill

doi:10.1016/0278-6915(92)90137-a

Cited by 26 publications

(10 citation statements)

References 5 publications

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“…However, in previous studies only 1-2% of the administered dose was recovered in faeces after both oral and dermal administration and only small amount were found in expired air and tissues (Wells and Digenis, 1988;Midgley et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

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Concentrations of N-methyl-2-pyrrolidone (NMP) and its metabolites in plasma and urine following oral administration of NMP to rats

Carnerup

Saillenfait

Jönsson

2005

Food and Chemical Toxicology

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The primary aims were to study the metabolism in rats and to determine the biological levels after one oral developmentally toxic dose of N-methyl-2-pyrrolidone (NMP), a widely used industrial chemical. Non-pregnant female Sprague-Dawley rats were given an oral single dose of either a non-toxic dose of 125 mg NMP/kg (group 1) by gavage or a developmentally toxic dose of 500 mg/kg (group 2). Blood plasma (7 rats per time point) and urine (10 rats per time point) were sampled up to 72h after administration and analyzed using mass spectrometry. In both plasma and urine NMP, 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP), N-methylsuccinimide and 2-hydroxy-N-methylsuccinimide (2-HMSI) and 2-pyrrolidone (2-P) were identified. In urine 48% of the administered dose was recovered as 5-HNMP and 2-5% as 2-HMSI. The total recovery in urine was 53-59%. The peak concentrations for NMP in plasma were 1.2 and 6.9 mmol/l, 0.42 and 0.76 mmol/l for 5-HNMP, 0.07 and 0.31 mmol/l for MSI and for 2-HMSI the concentrations were 0.02 and 0.05 mmol/l for group 1 and 2, respectively. In summary, the same metabolites were found in rats as in humans and the biological levels were reported for NMP and its metabolites after oral exposure to a developmentally toxic dose and one non-toxic dose of NMP.

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Section: Discussionmentioning

confidence: 99%

“…In the rat, an extensive oral (Midgley et al, 1992) and percutaneous (Midgley et al, 1992;Payan et al, 2003) uptake has been shown. The metabolism is unclear but Wells et al (1992) showed that the major urinary metabolite was 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP).…”

Section: Introductionmentioning

confidence: 99%

Concentrations of N-methyl-2-pyrrolidone (NMP) and its metabolites in plasma and urine following oral administration of NMP to rats

Carnerup

Saillenfait

Jönsson

2005

Food and Chemical Toxicology

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show abstract

“…A metabolic pathway in humans, where NMP is first hydroxylized to 5-HNMP and then further oxidized to N-methylsuccinimide (MSI), which in turn is hydrolyzed to 2-hydroxy-N-methylsuccinimide (2-HMSI), has been suggested (4). It has been shown that NMP possesses a high permeability through both human (5) and rat (6,7) skin. In rat, about 70% of the radioactivity of skin-administered radiolabeled NMP is excreted in urine (7).…”

mentioning

confidence: 99%

“…It has been shown that NMP possesses a high permeability through both human (5) and rat (6,7) skin. In rat, about 70% of the radioactivity of skin-administered radiolabeled NMP is excreted in urine (7).…”

mentioning

confidence: 99%

Biological monitoring of N-methyl-2-pyrrolidone using 5-hydroxy-N-methyl-2-pyrrolidone in plasma and urine as the biomarker

Åkesson¹,

Jönsson²

2000

Scand J Work Environ Health

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“…The present permeability test of the protective glove used in this study revealed that liquid NMP easily penetrates the protective gloves made of polyethylene. A sizable amount of NMP might be absorbed into the body through the skin of NMP-handling workers wearing such ineffective gloves in comparison with the amount of NMP absorbed through inhalation, since NMP is reported to be a substance with high percutaneous uptake 35) . Therefore, it can be inferred that a larger amount of NMP absorption through the skin in the real occupational setting than in the volunteer study hinders the positive correlation between the NMP exposure and the urinary NMP levels that would have otherwise been expected to occur in both the experimental and occupational settings.…”

Section: Discussionmentioning

confidence: 99%

A Cross-sectional Observation of Effect of Exposure to N-Methyl-2-Pyrrolidone (NMP) on Workers' Health

et al. 2009

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Percutaneous absorption of co-administered N-methyl-2-[14C]pyrrolidinone and 2-[14C]pyrrolidinone in the rat

Cited by 26 publications

References 5 publications

Concentrations of N-methyl-2-pyrrolidone (NMP) and its metabolites in plasma and urine following oral administration of NMP to rats

Concentrations of N-methyl-2-pyrrolidone (NMP) and its metabolites in plasma and urine following oral administration of NMP to rats

Biological monitoring of N-methyl-2-pyrrolidone using 5-hydroxy-N-methyl-2-pyrrolidone in plasma and urine as the biomarker

A Cross-sectional Observation of Effect of Exposure to N-Methyl-2-Pyrrolidone (NMP) on Workers' Health

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