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Toxicological information

Acute Toxicity: dermal

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Administrative data

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 Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
N-(n-octyl)-2-pyrrolidinone
EC Number:
403-700-8
EC Name:
N-(n-octyl)-2-pyrrolidinone
Cas Number:
2687-94-7
Molecular formula:
C12 H23 N O
IUPAC Name:
N-(n-octyl)-2-pyrrolidinone
Details on test material:
- Name of test material (as cited in study report): N-(N-Octyl)Pyrrolidone; Substance No. 91/453
- Physical state: colorless liquid
- Analytical purity: 99.3 %
- Lot/batch No.: 103/90
- Storage condition of test material: refrigerator

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: DR. K. Thomae GmbH, D-W7950 Biberach
- Age at study initiation: young adults
- Weight at study initiation: 150-300 g
- Fasting period before study: 16 hrs
- Housing: individual
- Diet: Kliba laboratory diet, Klingenthalermühle, Kaiseraugst, Switzerland ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk; about 50 cm²
- % coverage: 25-17 (calculated with a body surface area of 300-400 cm² depending on a body weight of 200-300 g as specified above)
- Type of wrap if used: semiocclusive dressing


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


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.43, 2.17, 4.34 ml/kg bw, respectively
- Concentration (if solution):
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
400, 2000, 4000 mg/kg
No. of animals per sex per dose:
5 males and females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least once daily on working days, recordings of signs and symptoms several times/day; once on weekends
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 000 mg/kg bw
Mortality:
In the highest dosing group 2 female animals died after one day and another female on day 2 after substance application.
Clinical signs:
Signs of toxicity noted in the 4000 mg/kg group comprised poor general state, dyspnoea, apathy, abdominal or lateral position, atonia, paresis, narcotic-like state, absent corneal and pain reflex, red-coloured urine and red-smeared fur in the anogenital area. The animals of the 2000 and 400 mg/kg dose group did not show any systemic signs of toxicity. After removal of the patches very slight to well-defined erythema, slight to moderate edema and hemorrhage could be observed in the high dose group. 7 days after application almost all animals showed scaling and one hemorrhage. Only scaling could be observed in almost all animals 14 days after application. In the mid dose group very slight to well-defined erythema and very slight edema were noticed after removal of the patches. 7 days after application a few animals exhibited very slight to well-defined erythema, very slight edema, scaling and severe scaling. 14 days after application only scaling was observed in 3 animals. In the low dose group no local effects could be seen.
Body weight:
all animals showed normal body weight gain
Gross pathology:
Animals that died (females)
4000 mg/kg (3 females)
general congestion
Liver intensified grayish-brown lobule liver pattern, partly confluent
Kidneys: black-brown tinge urine, bloody coloured

Histopathology:
4000 mg/kg (1 female):
Liver: increased lipid storage in the lobular periphery
Kidneys: acute necrosis of tubular cells in the cortex, focal fatty degeneration of tubular cells, diffuse
Urinary bladder: blood filled

Sacrificed animals: no pathologic findings noted

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU