1-ethyl-1-methylpyrrolidinium bromide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November-December 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study done under GLP using OECD guideline

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 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-ethyl-1-methylpyrrolidinium bromide

EC Number:

418-200-5

EC Name:

1-ethyl-1-methylpyrrolidinium bromide

Cas Number:

69227-51-6

Molecular formula:

C7H16NBr

IUPAC Name:

1-ethyl-1-methylpyrrolidin-1-ium bromide

Specific details on test material used for the study:

Cas # 69227-51-6
Batch # 0691
pH: 6-9
Storage: 5°C in the dark
Supplier: Chemson, Polymer-Additive Gesellschaft m.b.H. A-9601 Arnoldstein.
Characterization:
Appearance: Colorless liquid.
pH 6.84
Content 52.2% (estimation of bromide)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

OFA

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Forschungsinstitute fur Versuchstierzucht, A-2325 Himberg
- Age at study initiation: 8 weeks
- Weight at study initiation: 159-229 gr
- Housing: Single caging in Makrolon cages type III (39 cn x 23 cm x 15 cm). Wire mesh lids.
- Beeding material: Aspen wood chips, autoclaved.
- Diet (e.g. ad libitum): Altroxim 1314ff, gamma irradiated with 10 kGy 60 Co, ad libitum.
Exception: Feed was withdrawn the evening before application and was offered again about three hours after application.
- Water (e.g. ad libitum): tap water, offered in Markolon bottles with stainless steel canules, ad libitum.
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): average of 55%
- Air changes (per hr): 12 / hr
- Photoperiod (hrs dark / hrs light): artificial light from 6 am to 6 pm

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

- MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg
- Rationale for the selection of the starting dose: In a preliminary test (200 mg resp. 2000 mg test substance per kg body weight, 2 females each) animals survived at a dose of 200 mg for one week without any signs of malaise, but 1/2 animals died at a dose of 2000 mg within 2 hr p.a.
Based on this information and according to OECD guideline, 2000 mg/kg were chosen as high dose and 200 mg/kg as low dose for main study. The third dose was intrapolated geometrically.

Doses:

200, 632, 2000 (mg/kg b.w)

No. of animals per sex per dose:

5 males (one group) and 15 females (three groups of 5 each)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:10 min, 30 min, 1, 2, 4 and 6 hr after administration (p.a) and then at least once a day for a total of 2 weeks.
Body weight was determind before administration, 7 days p.a. and 14 days p.a. Body weights of early deaths were measured too, except for death on the of application.
Spontaneously died animals were dissected and examined macroscopically in an attempt to identify the target organs. All surviving animals were sacrificed by CO2 14 days p.a. and examined macroscopically in an attempt to detect possible residual lesions.

Statistics:

Analysis of variance followed by the Scheffe test: to compare body weight and body weight gain within the dosed group.
Calculation of LD50 was done according tho Thompson (Bac. Rev. 11 (1947))

Results and discussion

Preliminary study:

In a preliminary test (200 mg resp. 2000 mg test substance per kg body weight, 2 females each) animals survived at a dose of 200 mg for one week without any signs of malaise, but 1/2 animals died at a dose of 2000 mg within 2 hr p.a.
Based on this information and according to OECD guideline, 2000 mg/kg were chosen as high dose and 200 mg/kg as low dose for main study. The third dose was intrapolated geometrically.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: a calculation revealed a LD50 of about 2700 mg/kg b.w

Mortality:

1/5 males and 2/5 females of the high dosed groups died spontaneously within maximum 3 hr p.a. All other animals survived until the end of the study (14 day p.a)

Clinical signs:

Low dosed group: 3/5 animals were normal during the whole observation period. In the affected animals piloerection, an unspecific sign of malaise, and sedation were found.
Mid dosed group: all animals were affected. Piloerectionand incomplete eyelid closure, both unspecific signs of general malaise, as well as specific signs, i.e. sunken flanks, sadation and tremor were observed.
High dose grops: all animals were affected, pilorection, incomlete eye closure and chromodacryorrhoea, alltogether unspecific signs of general malaise, as well as specific signs, i.e. sunken flanks, salivation, cyanosis, tremor and clonic convulsions, sedation, dyspnoea and abnormal posture were observed. In the animals, which survuved until the end of the study, signs returned to normal within maximum 1 day p.a.

Body weight:

There were no significant differences between groups of females at schedualed examination terms.

Other findings:

Necropsy findings: At post mortem examination of early deaths alternations of glandular stomachs mucosa were found.
At terminal necropsy 4/5 low dosed, 3/5 mid dosed and 4/7 high dosed animals were normal.
In females a large spleen was found in one low dosed animal. A small spleen, alternations of glandular stomachs mucosa and large mesenteric lymph nodes were observed in mid dosed animals.
In the males, an alternation of glandular stomachs mucosa, a large spleen and large thyroids were noted in one animal each.
gastric irritation and spleen alternations were the findings related to the action of the test substance.
No sex differences in the response to the test material were elucidated.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (oral) of the test substance is higher than 2000 mg/kg b.w in both sexes of rats.
A claculation revealed a LD50 of about 2700 mg/kg b.w.
Specific toxic effects of the test substance are gastric irritation, circulatory problems and convulsions.

Executive summary:

A 50% aqueous solution of the test substance was administered once perorally to 5 males and 15 Him:OFA rats.

The test substance, diluted with distilled water, was applied by gavage to:

group 1 (low dose) 200 mg/kg b.w females

group 2 (mid dose) 632 mg/kg b.w females

group 3 (high dose) 2000 mg/kg b.w females

group 5 (high dose) 2000 mg/kg b.w males

The study was done according to OECD 401.

The study terminated after 14 days.

LD50 (oral) of the test substance is higher than 2000 mg/kg b.w in both sexes of rats.

A claculation revealed a LD50 of about 2700 mg/kg b.w.

Specific toxic effects of the test substance are gastric irritation, circulatory problems and convulsions.