CAS NO. 2687-91-4
TOXICITY:Oral Rat LD50:
SYNONYMS:1-Ethyl-2-pyrrolidinone; NEP; 1-éthylpyrrolidine-2-one;
Solvent, Pyrrolidine, Intermediate
PHYSICAL AND CHEMICAL
PHYSICAL STATE Clear, colorless liquid
MELTING POINT:< -75 C
BOILING POINT:97 at 20 mm Hg
WATER:Miscible (and soluble in other organic solvents.)
NFPA RATINGS:Health: 2 Flammability: 2 Instability: 0;
VAPOR PRESSURE:0.103 (mmHg)
(atm-m3/mole at 25 C)
OH RATE:2.54E-11 (cm3/molecule-sec at 25 C
REFRACTIVE INDEX :1.465 - 1.467
STABILITY:Stable under ordinary conditions.
GENERAL DESCRIPTION &
Pyrrolidone is a keto-pyrrole, that is a 5-membered lactam
structure compound (gamma-butyrolactam). Lactam structure compound including
pyrrolidone has good solvency property, therefore useful in industrial
application. It is an important part of antibiotics, such as penicillin. These
structures, cyclic esters and analogues, are active nucleuses in pharmacological
activity and flavorings. Lactams have big demand in artificial fibre industry.
They are polymerizable and used as nylon precursors. 2-Pyrrolidone is used as a
solvent for surface treatment for textiles, metal coated plastics, polymers, and
paint removing. Pyrrolidone and its derivatives are used as Intermediates for
the synthesis of agrochemicals, pharmaceuticals, textile auxiliaries,
plasticizers, polymer solvent, stabilizers, specialty inks and as a nylon
precursor. NMP is used as a solvent for paint stripping and resins; cleaner for
polymeric residues; metal finishing; printed circuit board manufacturing; SBR
latex production; pigment dispersant; extraction of acetylene and butadiene;
dehydration of natural gas; lube oil processing;
APPEARANCE clear to slightly yellow liquid
COLOR (APHA):50 max
HAZARD OVERVIEW:GHS (Globally
Harmonised System) Classification: Flammable liquids. Acute toxicity (Oral). Eye
irritation. Hazard statements: Combustible liquid. Harmful if swallowed. Causes
serious eye irritation.
P STATEMENTS:P305 +
P351 + P338
In accordance with Article 37 (4) of the Regulation (EC) No
1272/2008 (CLP Regulation),the Committee for Risk Assessment (RAC) has adopted
an opinion on the proposal for
harmonised classification and labelling of
Substance Name: N-ethyl-2-pyrrolidone (NEP)
SCIENTIFIC GROUNDS FOR THE
The opinion relates only to those hazard classes that have been
reviewed in the proposal for harmonised classification and labelling, as
submitted by France.
N-ethyl-2-pyrrolidone is an industrial solvent, catalyst
and surfactant. A classification proposal relating to the reproductive toxicity
has been submitted by France as follows.
No other endpoint will be
addressed.Proposal of the dossier submitter Reproductive Toxicity
significant data base of experimental animal studies were submitted by the
notifier and evaluated by the dossier submitter (DS). These include both dermal
(BASF 2010) and oral
gavage ( BASF 2007a/BASF 2007b) studies in the rabbit
and oral gavage (Saillenfait 2007) and dermal (BASF 2005) studies carried out in
the rat. All data were either compliant or
consistent with current OECD
guidelines. In addition, the developmental profile of a closely related
substance N-methyl-2-pyrrolidone (NMP) currently classified as Cat 1B H360 (1st
ATP CLP) and Repr. Cat.2; R61 (31st ATP Directive 67/548/EEC and) was included
for comparative purposes. Based on the animal studies carried out, it was
that N-ethyl-2-pyrrolidone(NEP) induces:
effects on foetal body weights in rabbits by oral route, in rats by dermal route
and in rats by oral route
- effects on post-implantation loss and in
particular late resorptions in rats by oral route.
- malformations in rabbits
by dermal and oral route and in rats by oral route.There was a significant
increase in skeletal malformations by oral route in both rats and rabbits.
Besides, rare cardiovascular malformations were observed above historical
controls in rabbit by dermal and oral routes and in rats by oral route. On this
basis, it is concluded that there is clear evidence of teratogenic and
foeto-toxic effects of N-ethyl-2-pyrrolidone(NEP).
Developmental effects of
N-ethyl-2-pyrrolidone(NEP) and in particular the profile of malformations
observed in the rat by oral route, are similar to the developmental effects
observed with NMP, which
strengthen the weight of evidence that the effects
observed in the N-ethyl-2-pyrrolidone(NEP) studies are related to administration
of the test substance.
It is noted that the decrease in foetal weight in the
rat and in the rabbit by oral route, the induction of late resorptions in the
rat by oral route and of malformations in rabbit by dermal and oral route and in
rat by oral route cannot be correlated to a limited maternal toxicity.
maternal toxicity was clearly demonstrated, the possibility that the serious
specific malformations and developmental toxicity may be treatment-related
cannot the discounted.
Such an effect must be critically assessed
irrespective of maternal toxicity. Such malformations and other adverse
developmental effects observed cannot be considered as consequential on maternal
toxicity. The similarity of effects between N-ethyl-2-pyrrolidone(NEP) and NMP
also support that these effects are an intrinsic property of these
A classification Repr. 1B –H360D is warranted (Repr. Cat. 2; R61
according to Directive 67/548/EEC). As no developmental study is available by
inhalation, it is proposed not to
specify route of exposure in the hazard
Guidelines to set specific concentration limits (SCL) for
reproductive toxicity are currently under discussion. In absence of adopted
guidelines at this point in time, no SCL are proposed.
during the public consultation
The comments received from a number of Member
States were in support of the dossier submitter’s classification proposal. A
number of Member State Competent Authorities
(MSCAs) pointed out that the
designation of H360D instead of the general statement H360 was incorrect.
According to the CLP Guidance Document (Section 126.96.36.199) only the
statement can be applied in the absence of specific reliable and
adequate data on fertility which excludes this effect. This point was agreed by
the DS and the draft of CLH report was amended accordingly.
comment was in general support of the classification proposal. A reference was
made by the industry federation CEFIC to new data (28 day inhalation study OECD
which they considered relevant to fertility (CEFIC 6/5/2011 Annex 2
Reference was also made to a 2 generation study protocol.
Industry suggested that the current consultation should await the results of
these studies when completed. In addition, it was proposed that due to
similarity (structural and toxicity profile) to NMP which is classified as GHS
Repro. Cat 1B H360D with a specific concentration limit of >5%, the same
concentration limit should be applied to N-ethyl-2-pyrrolidone(NEP).
of RAC consultation
RAC supports the classification proposal of the dossier
submitter.The original labelling proposal of the dossier submitter was
allocation of H360D, which was amended to H360 in the revised CLH Report
following comments made during the public consultation. There were different
opinions on this issue raised at RAC 17 and during the written follow up
(ORCOM). RAC agreed upon the allocation of ‘D’ to specify the development
endpoint, i.e., H360D. This is in line with a number of previous RAC
recommendations where only one of the two reproductive endpoints has been
addressed. The rationale is that the relevant positive adverse effect should be
identified in the labelling phrase to offer greater protection to the user, even
though it is acknowledged that this procedure is not strictly in line with the
The Background Document, attached as Annex 1, gives the detailed
scientific grounds for the Opinion.