Developmental toxicity of N -methyl-2-pyrrolidone in rats following inhalation exposure

Saillenfait, Anne-Marie; Gallissot, F.; Morel, G.

doi:10.1016/s0278-6915(02)00300-9

Cited by 51 publications

(38 citation statements)

References 14 publications

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“…In contrast to the severe prenatal effects found in oral and dermal studies, exposure of pregnant rats to vapours of NMP on GD 6-20 resulted in developmental toxic effects limited to fetal growth retardation (Becci et al, 1982;Hass et al, 1995;Saillenfait et al, 2003). These occurred in the presence of maternal toxicity.…”

Section: Discussionmentioning

confidence: 84%

Developmental toxic effects of N‐ethyl‐2‐pyrrolidone administered orally to rats

Saillenfait

Gallissot

Sabaté

2007

J of Applied Toxicology

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The developmental toxicity of N-ethyl-2-pyrrolidone (NEP) was studied in Sprague-Dawley rats after oral administration. Pregnant rats were given NEP at doses of 0 (distilled water), 50, 250, 500 and 750 mg kg(-1) day(-1), by gavage (5 ml kg(-1)), on gestational days (GD) 6-20. Maternal toxicity, as evidenced by reduction in body weight gain and food consumption, was observed in all NEP groups at the beginning of treatment (GD 6-9). The incidence of resorptions was significantly increased at 500 mg kg(-1) day(-1), and reached 83% at 750 mg kg(-1) day(-1). There was a dose-related decrease in fetal weight, which was significantly lower than control at 250 mg kg(-1) day(-1) and higher doses. The incidence of malformed fetuses per litter and the number of litters with malformed fetuses were significantly increased at 500 and 750 mg kg(-1) day(-1). Malformations mainly consisted of edema, anal atresia with absent tail, cardiovascular defects and fused cervical arches. Ossification of skull bones and sternebrae was significantly reduced at 500 and 750 mg kg(-1) day(-1). The incidence of supernumerary ribs was significantly elevated at 250 mg kg(-1) day(-1) and higher doses. In conclusion, NEP administered by gavage is embryotoxic and teratogenic at maternal toxic doses.

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Section: Discussionmentioning

confidence: 84%

Developmental toxic effects of N‐ethyl‐2‐pyrrolidone administered orally to rats

Saillenfait

Gallissot

Sabaté

2007

J of Applied Toxicology

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“…Furthermore, in rats, NMP have been reported to be a developmentally toxic compound after dermal and oral administration (Becci et al, 1982;Hass et al, 1995;Saillenfait et al, 2002). Retarded growth has been reported after inhalation exposure (Saillenfait et al, 2003). It is unclear whether it is NMP itself or some of its metabolites that cause this effect.…”

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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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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“…However, recent findings indicate that NMP has aquatic toxicity for Daphnia magna, with a 50% lethal concentration at 24 h of 1.23 mg ⅐ liter Ϫ1 , and only certain pesticides have greater toxicity than this compound (23). NMP has been reported to be teratogenic in rats when administered orally (38) but not by inhalation (16,25,37), although a reduction in fetal weight has been observed to occur in the absence of obvious maternal effects at certain doses (37,43). It has also been correlated with stillbirth in a woman working in a laboratory where NMP was used routinely (42) and with the poisoning of an agricultural worker by an insecticide in which it was a major component (44).…”

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confidence: 99%

Characterization of the Polyurethanolytic Activity of Two Alicycliphilus sp. Strains Able To Degrade Polyurethane and N -Methylpyrrolidone

Oceguera-Cervantes

Carrillo-García

López

et al. 2007

Appl Environ Microbiol

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Two bacterial strains (BQ1 and BQ8) were isolated from decomposed soft foam. These were selected for their capacity to grow in a minimal medium (MM) supplemented with a commercial surface-coating polyurethane (PU) (Hydroform) as the carbon source (MM-PUh). Both bacterial strains were identified as Alicycliphilus sp. by comparative 16S rRNA gene sequence analysis. Growth in MM-PUh showed hyperbolic behavior, with BQ1 producing higher maximum growth (17.8 ؎ 0.6 mg ⅐ ml ؊1 ) than BQ8 (14.0 ؎ 0.6 mg ⅐ ml ؊1 ) after 100 h of culture. Nuclear magnetic resonance, Fourier transform infrared (IR) spectroscopy, and gas chromatographymass spectrometry analyses of Hydroform showed that it was a polyester PU type which also contained N-methylpyrrolidone (NMP) as an additive. Alicycliphilus sp. utilizes NMP during the first stage of growth and was able to use it as the sole carbon and nitrogen source, with calculated K s values of about 8 mg ⅐ ml ؊1 . Enzymatic activities related to PU degradation (esterase, protease, and urease activities) were tested by using differential media and activity assays in cell-free supernatants of bacterial cultures in MM-PUh. Induction of esterase activity in inoculated MM-PUh, but not that of protease or urease activities, was observed at 12 h of culture. Esterase activity reached its maximum at 18 h and was maintained at 50% of its maximal activity until the end of the analysis (120 h). The capacity of Alicycliphilus sp. to degrade PU was demonstrated by changes in the PU IR spectrum and by the numerous holes produced in solid PU observed by scanning electron microscopy after bacterial culture. Changes in the PU IR spectra indicate that an esterase activity is involved in PU degradation.Polyurethane (PU) was developed by Otto Bayer as a substitute for rubber at the beginning of World War II (1938). Due to its range of properties, the polymer is widely used, for example, in liquid coatings and paints, adhesives, sealants, flexible and rigid foams, and elastomers (7). Since PU is such a versatile polymer, PU production has increased, but this has brought with it the problem of safe disposal. Each year, more than 5 million tons of shredder residue containing different plastics and PU foams is generated in the United States and Canada (6). Several mechanical processes, such as regrinding, flexible foam bonding, adhesive pressing, and compression molding, as well as chemical techniques, such as glycolysis, hydrolysis, pyrolysis, and hydrogenation, are used for the recovery of the starting materials or in the production of other PU types (8). Recently, the development of new strategies based on the utilization of biopolymers such as poly[(R)-hydroxyalkanoic acids] (21), the enzymatic polymerization of polyesters and degradation of PU (28), and the discovery of microorganisms (fungi and bacteria) able to utilize PU as a source of carbon and nitrogen (12,31,32) is leading the move to a greener chemical industry.A number of bacterial strains, such as Corynebacterium sp., Pseudomonas fluorescens, P. ch...

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Developmental toxicity of N -methyl-2-pyrrolidone in rats following inhalation exposure

Cited by 51 publications

References 14 publications

Developmental toxic effects of N‐ethyl‐2‐pyrrolidone administered orally to rats

Developmental toxic effects of N‐ethyl‐2‐pyrrolidone administered orally to rats

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

Characterization of the Polyurethanolytic Activity of Two Alicycliphilus sp. Strains Able To Degrade Polyurethane and N -Methylpyrrolidone

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