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Administrative data

Link to relevant study record(s)

Description of key information

Since it is likely that N-(2-Hydroxyethyl)-2-pyrrolidon will be absorbed, and in the absence of substance-specific absorption data, the default absorption values from the REACH guidance (Chapter 8, R.8.4.2) are used for DNEL derivation, namely: 100% for inhalation and 50% for oral absorption. As both oral and dermal absorption are expected to be low a default factor of 1 for oral-to-dermal extrapolation was used for DNEL derivation.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

Since no toxicokinetic studies are available for N-(2-Hydroxyethyl)-2-pyrrolidon, therefore relevant substance properties and data from toxicity studies indicating systemic bioavailability were taken together to assess the general toxicokinetics of the substance.

Physical-chemical properties.

N-(2-Hydroxyethyl)-2-pyrrolidon is a colorless to yellow liquid at room temperature, a boiling point of 309°C, and a molecular weight of 129.157 g/mol. The log Pow value is is - 1.03 at 25°C, the vapour pressure is 0.0002 hPa, and the substance is very soluble in water (miscible with water at 20°C at any ratio).

Data from acute and repeated dose toxicity studies

Oral toxicity

In an acute oral toxicity study in rats, exposure to 200, 1600, 3200 or 6400 mg/kg bw N-(2-Hydroxyethyl)-2-pyrrolidon resulted inno mortalityand necropsy of the sacrificed animals was without findings. The clinical findings reported included restlessness and dyspnea at the two highest dose levels tested. The LD50 was determined to be >6400 mm3/kg bw (>7300 mg/kg bw) for both sexes. (BASF AG, 1970). In a GLP compliant combined 28-days repeated dose toxicity study with reproduction/developmental toxicity screening test, N-(2-Hydroxyethyl)-2-pyrrolidon was given to rats by oral gavage at dose levels of 100, 300 and 1000 mg/kg bw/day (BASF SE, 2013). No adverse clinical findings were noted. In several male and female high-dose parental animals, salivation was observed after treatment throughout major parts of the treatment period, including the gestation and lactation periods. Since this salivation was transient and occurred directly after dosing, it is probably due to the irritation and/or taste of substance administration, and therefore was not assessed as adverse. No changes in either food consumption or body weight parameters were noted at any dose. Regarding clinical pathology, no treatment-related, adverse effects were observed up to the 1000 mg/kg bw/d dose of the compound. Regarding pathology, no treatment-related organ weight changes, gross lesions or histopathological findings were observed in the parental animals. All organs of the reproduction tract were not affected by treatment. No alterations to parental reproductive performance or fertility were observed at any dose. 

Inhalation toxicity

In an acute inhalation toxicity study in which rats were exposed for saturated vapour of the N-(2-Hydroxyethyl)-2-pyrrolidon at 20 ºC for 8 hours, no mortality was observed (BASF AG, 1970). 

Dermal toxicity

In an acute dermal toxicity study in rabbits, exposure to 2000 mg/kg bw N-(2-Hydroxyethyl)-2-pyrrolidon for 24 hours under semi-occlusive conditions did not result in mortality (Bioassay, 2012). The LD50 was determined to be greater than 2000 mg/kg bw.

Absorption figures used for the DNEL derivation

The results of the acute oral and the repeated dose oral toxicity study with reproduction/developmental toxicity screening test indicate absorption of the test substance by the oral route. Secondly, N-(2-Hydroxyethyl)-2-pyrrolidon’s high water solubility, low Log Pow and low molecular weight suggests that N-(2-Hydroxyethyl)-2-pyrrolidon may be readily absorbed by the gastrointestinal and respiratory tract. The log Pow of -1.03 and the high water solubility suggest that the substance may not be easily taken up by the stratum corneum. This is further substantiated by the lack of systemic effects observed in the acute dermal toxicity study performed with the test substance (Bioassay, 2012). In addition, as the substance is not a skin irritant (BASF AG, 1970) and has no sensitising properties (Harlan CCR, 2012). Further strengthening the suggestion that dermal uptake of the test substance will be low.

Since it is likely that N-(2-Hydroxyethyl)-2-pyrrolidon will be absorbed, and in the absence of substance-specific absorption data, the default absorption values from the REACH guidance (Chapter 8, R.8.4.2) are used for DNEL derivation, namely: 100% for inhalation and 50% for oral absorption. As both oral and dermal absorption are expected to be low a default factor of 1 for oral-to-dermal extrapolation was used for DNEL derivation.