Evaluation of Reproductive Disorders in Female Rats Exposed to N‐Methyl‐2‐Pyrrolidone

Abstract

Fertility index did not significantly differ in the control and the group exposed at 150 mg/kg/day but it was significantly lower in the groups exposed at 450 or 1000 mg/kg/day. The number of live pups in the group exposed to the highest dose was significantly lower and the number of stillbirths in litters was significantly greater. Survival of the pups from all exposed groups during the 3 weeks after birth was significantly lower than the control animals. The results of our study indicate that intragastric exposure of female rats to NMP before pregnancy during gestation causes significant impairment in female fertility and intrauterine mortality rates. At lower doses, toxic or slightly toxic to the mothers, this substance causes decrease in viability and physical development of progeny.

The European Human Biomonitoring Initiative (HBM4EU): Human biomonitoring guidance values (HBM-GVs) for the aprotic solvents N-methyl-2-pyrrolidone (NMP) and N-ethyl-2-pyrrolidone (NEP)

“…Furthermore, even in the available studies with whole-body inhalation exposure, uncertainties exist regarding the amount of additional dermal and oral intake, so that results from studies with oral exposure were considered more appropriate to derive HBM-GVs. For NMP the oral developmental toxicity study from Saillenfait et al (2002) on rats was chosen as key study and in addition the study from Sitarek et al (2012) as supporting study. The oral rat study of Sitarek et al (2012) refers to reproductive toxicity and shows effects on dams (reduced body weight) and offspring (reduced survival rate) at all doses tested.…”

“…For NMP the oral developmental toxicity study from Saillenfait et al (2002) on rats was chosen as key study and in addition the study from Sitarek et al (2012) as supporting study. The oral rat study of Sitarek et al (2012) refers to reproductive toxicity and shows effects on dams (reduced body weight) and offspring (reduced survival rate) at all doses tested. The study of Saillenfait et al (2002) resulted in a NOAEL of 125 mg/kg bw/d for maternal and developmental effects, that was only slightly below the 150 mg/kg bw/d that showed already maternal and developmental effects in the study of Sitarek et al (2012) (see Table 1 ).…”

“…The oral rat study of Sitarek et al (2012) refers to reproductive toxicity and shows effects on dams (reduced body weight) and offspring (reduced survival rate) at all doses tested. The study of Saillenfait et al (2002) resulted in a NOAEL of 125 mg/kg bw/d for maternal and developmental effects, that was only slightly below the 150 mg/kg bw/d that showed already maternal and developmental effects in the study of Sitarek et al (2012) (see Table 1 ). Because no NOAEL was identified from the study by Sitarek et al (2012) and the LOAEL is of the same order of magnitude as the identified NOAEL from the study by Saillenfait et al (2002) , an assessment factor (AF) of 3 was considered appropriate for application to the NOAEL of 125 mg/kg bw/d from the study by Saillenfait et al (2002) to account for uncertainties in the underlying database, thus leading to a value of 42 mg/kg bw/d.…”

Stoffmonographie für N-Methyl-2-pyrrolidon (NMP) und „Human-Biomonitoring“-Werte für die Metaboliten 5-Hydroxy-NMP und 2-Hydroxy-N-methylsuccinimid im Urin von Erwachsenen und Kindern

“…Das wissenschaftliche Komitee für Verbrauchersicherheit der EU (SCCS) hat in seiner Bewertung von NMP [3] keine tolerable Dosis abgeleitet, zieht aber den NO-AEL von 125 mg/(kg KG × d) aus der Studie zur Entwicklungstoxizität von Saillenfait et al [53] sowie Exxon [55] zur Abschätzung der "Margin of Safety" (MOS) heran. In der Bewertung des SCCS [3] konnte allerdings die erst später veröffent-lichte Studie von Sitarek et al [50] …”

Magnetic Hyperthermia Ablation of Tumors Using Injectable Fe3O4/Calcium Phosphate Cement

“…NMP is on the list of chemicals known to the state to cause cancer or preproductive toxicity cited in California proposition 65 (1986) . [14][15] Moreover, S-Fe/PLGA at low PLGA/NMP ratio will leak into the blood resulting in thrombus in vasculature, which cause potential safety concerns.…”