Pyrrolidine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1978

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study was performed before test guidelines and GLP principles were in place. Missing information and shortcomings in the methods: no details on tet substance (Lot/ batch nr., Cas no.) provided; Only 4 animals per concentration tested instead of 5 as described in the guideline (half of the animals tested had abraded skin, results from these animals can be considered as worst case). Two exposed and one control rabbit suffered from diarrhoea and died, it cannot be excluded that the health status of all animals was comprised.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Principles of method if other than guideline:

Male and female used in parallel; skin of half of the animals used was abraded; total number of animals per concentration = 4 instead of recommended 5; coverage occlusive instead of semi-occlusive; clinical observations not recorded.

GLP compliance:

no

Remarks:

Test was conducted before GLP guidelines were described.

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Pyrrolidine

EC Number:

204-648-7

EC Name:

Pyrrolidine

Cas Number:

123-75-1

Molecular formula:

C4H9N

IUPAC Name:

pyrrolidine

Details on test material:

- Name: Pyrrolidine
- Storage conditions: in the dark at room temperature.
- Analytical purity: not described
- Lot/batch no.: not described

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not described
- Age at study initiation: not described
- Weight at study initiation: 2.23-3.10 kg
- Fasting period before study: no
- Housing: individually
- Diet: ad libitum, standard laboratory diet
- Water: ad libitum, tap water
- Acclimation period: not described

ENVIRONMENTAL CONDITIONS
- Temperature (°C): appr. 18

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: trunk (abraded or intact)
- % coverage: 10% of total body surface
- Type of wrap if used: thin layer of cellulose sheet, wrapped in polyethylene foil

REMOVAL OF TEST SUBSTANCE
- Washing: water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 9ml/kg bw
- Constant volume used: yes

Duration of exposure:

24 hours

Doses:

0; 0.17; 0.35; 0.7 ml/kg

No. of animals per sex per dose:

2 (one with abraded and one with intact skin)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: at day 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, food and water consumption, haematology (haemoglobin, packed cell volume, red blood cells, white blood cells), histopathology (heart, liver, kidneys, spleen and treated and untreated skin)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 0.35 - < 0.7 mL/kg bw

Based on:

test mat.

Remarks on result:

other: Based on exposure via abraded or intact skin.

Mortality:

In the course of the observation period one control rabbit and two rabbits of the 0.17 ml/kg dose group suffered from diarrhoea and died.The rabbits of the high-dose group died or were killed during the exposure period or on the first day of the subsequent observation period. No further mortality occurred.

Clinical signs:

No abnormalities were observed in the control group. At 0.17 ml/kg, slight to moderate erythema, focal haemorrhages were seen. At 0.35 ml/kg, animals had slight to moderate erythema and ederna, extensive haernorrhages, tremors and sialorrhoea. At 0.7 ml/kg, slight to moderate erythema and edema, extensive haemorrhages, tremors, sialorrhoea, apathy, paresis and/or paralysis were recorded.
In the period following exposure, scaliness and necrotic skin was seen in all exposed animals. There were no distinct differences in reactions either between rabbits treated on the intact or abraded skin, or between male and female rabbits.

Body weight:

No significant differences in growth were found between treated and untreated animals.

Gross pathology:

At autopsy the treated skin of the test animals was found to be distinctly affected by the compound under study. The skin lesions, which were mainly characterized by necrosis, acanthosis, hyperkeratosis, fibroblastic activity and focal infiltrates of mainly mononuclear inflawnatory celIs, were most pronounced in the two higher dose groups. Microscopy of liver, kidneys, heart and spleen did not disclose any abnormalities that could be related to treatment.

Other findings:

No significant differences in water or food intake were found between treated and untreated animals. Haematological data of the surviving rabbits of the test groups were comparable with those of controls.

Any other information on results incl. tables

Signs of diarrhea were found in one additional control animal that survived and in two animals of the highest dose group that did not survive.