N-(n-octyl)-2-pyrrolidinone

Endpoint summary

Description of key information

The acute oral toxicity and the acute dermal toxicity of the test substance were investigated in Wistar rats, both studies were performed according to the respective OECD guidelines. 
- oral: LD50 (rat) > 2200 mg/kg bw
- dermal: LD50 (rat) > 4000 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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

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

Route of administration:

oral: gavage

Vehicle:

other: solution in olive oil DAB 9

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 and 44 g/100 ml
- Amount of vehicle (if gavage): 5 ml/kg
- Justification for choice of vehicle: test substance is insoluble in water


MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg

Doses:

1000, 2200 mg/kg

No. of animals per sex per dose:

5 males and females per dose level

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
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 200 mg/kg bw

Mortality:

no death occurred in any of the dosing groups

Clinical signs:

other: In male animals no clinical signs were noted in the 1000 mg/kg dosing group, female animals showed dyspnoea, apathy, abdominal position, staggering, piloerection exsiccosis and exophthalmos and poor general state in the first 4 hours after dosing. In the

Gross pathology:

no pathologic findings noted

Interpretation of results:

not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 200 mg/kg bw

Quality of whole database:

GLP, OECD guideline study

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 Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Limit test:

no

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

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

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

Interpretation of results:

not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

4 000 mg/kg bw

Quality of whole database:

GLP, OECD guideline study

Additional information

Acute oral toxicity:

The acute oral toxicity of the test substance was investigated in two groups of 5 male and 5 female rats, given a dose of 2200 and 10 female rats given a dose 1000 mg/kg bw as gavage (GLP OECD401 study, 1992_RL1). Signs of toxicity noted in the higher dosing group included poor and impaired general state, dyspnoea, apathy, lateral position staggering, paresis narcotic-like state, absent pain and corneal reflex cyanosis exsiccosis, chromodacryorrhea and red adhesive snout. Signs of toxicity of the lower dose included poor general state, dyspnoea, apathy, abdominal position staggering and exophthalmos. No death occurred and all animals appeared to be normal within 3 days after application. No abnormalities were noted at necropsy. under the conditions of the study the acute oral median lethal dose was found to be greater than 2200 mg/kg bw for male and female animals.

In a supporting study (GLP, similar to OECD guideline, 1986_RL1) the oral LD50 in rats was 2050 mg/kg bw.

Acute inhalation toxicity

Appropriate data to assess the acute inhalation toxicity of the test article are not available.

Acute dermal toxicity

The acute dermal toxicity of the test substance was investigated in three groups of 5 male and 5 female rats (OECD guideline 402, 1992_RL1). The test material was applied unchanged to the clipped epidermis of each animal at dose levels of up to 4000 mg/kg bw under semiocclusive conditions for 24 hours. Signs of toxicity were only noted for the highest dosing group including poor general state, dyspnoea, apathy, abdominal or lateral position, atonia, paresis, narcotic like state, absent corneal and pain reflex and red coloured excrements. After removal of the patch signs of skin irritation were visible. Signs of general toxicity was not observed for the lower dosing groups. In the highest dosing group 3 females died 1 or 2 days after application of the test substance wile no deaths were recorded for the lower dosing groups. Necropsy findings included general congestion, intensified grayish-brown partly confluent lobule marking of the liver black-brown colouring of the kidneys and bloody coloured urine. Histopathological examination identified the kidney and the urinary tract as the main targets of toxicity in one female animal. Under the conditions of the study conducted, the median LD50 of the test material was found to be greater than 4000 mg/kg bw for male animals, while the LD50 for female animals was found to be about 4000 mg/kg bw.

In a supporting study (similar to OECD guideline, 1986_RL1) the dermal LD50 in rabbits was > 2000 mg/kg bw.

Justification for classification or non-classification

According to EC/1272/2008, the test substance needs not to be labelled for acute toxicity.