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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:
1-octylpyrrolidin-2-one
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:
other: 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 anogenita
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