Registration Dossier

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral
Remarks:
other: Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: The data from the migrated NONS file is deficient, and the study has not been seen to confirm reliability. No guideline or GLP data has been provided, so the study could be highly unreliable.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA
Principles of method if other than guideline:
Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA
GLP compliance:
not specified
Remarks:
Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
corn oil
Details on oral exposure:
Method of administration: oral gavage (intragastric intubation)
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA
Duration of treatment / exposure:
28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 5 mg/kg bw/day
Male: 5 animals at 55 mg/kg bw/day
Male: 5 animals at 320 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 5 mg/kg bw/day
Female: 5 animals at 55 mg/kg bw/day
Female: 5 animals at 320 mg/kg bw/day
Details on study design:
Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA
Positive control:
Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA

Examinations

Observations and examinations performed and frequency:
Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA
Sacrifice and pathology:
Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA
Other examinations:
Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA
Statistics:
Not given in information from migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
No mortalities. 5 mg/kg bw/day: females showed increased salivation. 55 mg/kg bw/day: increased salivation and a hunched posture was observed. 320 mg/kg bw/day: increased salivation, hunched posture, abnormal gait (waddling), lethargy were observed.
Mortality:
mortality observed, treatment-related
Description (incidence):
No mortalities. 5 mg/kg bw/day: females showed increased salivation. 55 mg/kg bw/day: increased salivation and a hunched posture was observed. 320 mg/kg bw/day: increased salivation, hunched posture, abnormal gait (waddling), lethargy were observed.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Lower for females in the high dosage group.
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Lower PCV and RBC counts, higher MCHC for males at 320 mg/kg bw/day. Higher neutrophil counts for females at 55 mg/kg bw/day, males and females at 320 mg/kg bw/day.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
GPT higher in females at 320 mg/kg bw/day. Lower albumin levels (and A/G ratios) for males at 55 and 320 mg/kg bw/day. Lower Ca levels for males at 320 mg/kg bw/day. Lower Cl levels for males at all levels.
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Similar to those of the controls.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
No macroscopic changes related to treatment.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
No histopathological changes related to treatment.
Histopathological findings: neoplastic:
not specified
Details on results:
No further details provided in the migrated NONS file as per inquiry # [06-0000024772-67-0000], permission to refer granted by ECHA

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
ca. 55 mg/kg bw/day (nominal)
Based on:
other: Original NCD unit is mg/kg/day
Sex:
not specified
Dose descriptor:
NOEL
Effect level:
ca. 55 mg/kg bw/day (nominal)
Based on:
other: original NCD unit is mg/kg/day
Sex:
not specified

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
N-(n-octyl)-2-pyrrolidinone is not classified.
Executive summary:

The migrated NONS file does not provide details on the guideline followed, or whether the study is GLP. The NOEL and NOAEL are both found to be 55 mg/kg bw/day. This is not at a level which provides a classification.