Registration Dossier

Administrative data

Description of key information

Acute toxicity data indicate a low toxicity: in rats the oral LD50 was >7300 mg/kg bw and the dermal LD50 was >2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401. A test group consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Gassner
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test substance was administered as 2, 20 or 30% (v/v) aqueous solution.
Doses:
200, 1600, 3200, 6400 mm3/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 6 400 other: mm3/kg bw
Based on:
test mat.
Remarks on result:
other: original value
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 300 mg/kg bw
Based on:
test mat.
Remarks on result:
other: calculated from original value
Mortality:
No mortality was observed.
Clinical signs:
At the two higest dose levels: restlessness and dyspnea.
Body weight:
No details given in the study report.
Gross pathology:
No abnormalities were detected.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, available as unpublished report, fully adequate for assessment.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: males, 8 weeks; females, 12 weeks
- Weight at study initiation: males, 233 g; females, 211 g
- Fasting period before study: no
- Housing: single housing in Makrolon cage, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 – 70
- Air changes (per hr): fully air-conditioned room
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 40 cm2
- % coverage: 10
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze and stretch bandage)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.75 mL/kg bw
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights were determined before administration (day 0), weekly thereafter and on the last day of observation; clinical signs were recorded several times on the day of administration and at least once daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: skin irritation
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
No systemic clinical signs observed.
Local effects were not observed in males. In females, slight erythema (grade 1) was observed in all animals starting on study day 1 until day 2, 5 or 6 (1 animal each) or until day 14 (2 animals). In 4 out of 5 females a significant scratching behaviour was observed on study day 5. The 2 animals, which showed erythema until day 14 also exhibited incrustations from day 6 to day 14. No edema was noted.
Body weight:
The mean body weight increased within the normal range.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Oral toxicity In an acute oral toxicity study comparable to OECD guideline 401 (BASF AG, 1970), Gassner rats (5/sex/dose) were exposed to dose levels of 200, 1600, 3200 or 6400 mm3/kg bw 1-(2-hydroxyethyl)-2-pyrrolidone by gavage and observed for 14 days. The only clinical findings reported included restlessness and dyspnea at the two highest dose levels tested. No mortality was observed at any dose level and necropsy of the sacrificed animals was without findings. The LD50 was determined to be >6400 mm3/kg bw (>7300 mg/kg bw) for both sexes. Inhalation toxicity In an acute inhalation toxicity study, according to the BASF-internal standard (a protocol comparable to OECD guideline 403) in which rats (n=12/sex) were exposed to a saturated vapour of the substance at 20 ºC for 8 hours, no deaths were observed during a 7 days observation period (BASF AG, 1970). Due to the low vapour pressure, the technically highest attainable concentration is approximately 0.008 mg/L when the test substance is evaporated at 20°C (concentration not determined), which is below cut off values for classification / any limit concentration.   Dermal toxicity In an acute dermal toxicity study (Limit Test) in accordance with OECD Guideline 402 and under GLP, young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item N-(2-Hydroxyethyl)-2-pyrrolidon on the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours (Bioassay, 2012). The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred at the tested concentrations therefore the LD50 was determined to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

Based on the result of the available acute oral and dermal toxicity studies, 1-(2-hydroxyethyl)-2-pyrrolidone does not need to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.