1-ethyl-1-methylpyrrolidinium bromide

Endpoint summary

Description of key information

Oral: 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.

Dermal: All animles survived until termination.

No toxicological signs were observed during the test and  obervations which were  noted were not of toxicological importance.

Therefore LD50 of the test substance was > 2000 mg/kg b.w

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

Study period:

November-December 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study done under GLP using OECD guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

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)

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Exception: Feed was withdrawn the evening before application and was offered again about three hours after application.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

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))

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 700 mg/kg bw

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

Study period:

July-December 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study done under GLP and OECD guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

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)

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Him: OFA

Sex:

male/female

Details on test animals or test system and environmental conditions:

Supplier: Forscungsinstitute fur Versuchstierzucht, A-2325 Himbera.
Number in the study: 5 males and 5 females
Age: approx. 8 weeks (males) and 12 weeks (females) at time of administration.
Body weight: 245 gr (mean, males), 230 (mean, females)
Hygiene: imporoved conventional conditions
room temperature: average of 12 °C.
Relative humidity: average of 55%
Air exchange 12 / h
Light: artificial light from 6 am to 6 pm
Cages: single caging in Makrolon cages type III . Wire mesh lids.
Bedding material: Aspen wood chips, autoclaved
Feed: Altromin No. 1314 ff, gamma irradiated with 10 kGy 60Co, ad libitum.
Water: tap water, offered in Makrolon bottles with stainless steel canules, ad libitum.
Acclimatization: 7 days

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Dermal administration was performed once in the morning by spreading the test substance over an area of approx. 5 cm x 6 cm which is at least 10% of the body surface.
Hair was clipped one day before the application with an electric hair clipper. The test site was median on the dorsal thoracal region.
The administrated test substance was covered by cellulose patch and held in place by non irritating tape. Patch and tape were covered by a dressing.

Duration of exposure:

The duration of the exposure was 24 hr
At the end of the exposure period the dressing the tape and the patch were removed. residual test substance was wiped off using wet cellulose tissue.

Doses:

2000 mg/kg b.w

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

Behaviour, reactions and physical signs of the animals were observed 10, 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 determined before administration, 7 days p.a. and 14 days p.a.
All animles were sacrificed by CO23 14 days p.a. and examined macroscopically in an attempt to detect possible residual lesions.

Statistics:

n/a

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality

Body weight:

Body weight and body weight gain were inconspicuous in all males and in 2/5 females. In the other females a body weight loss respectively a lower body weight gain as compared to untreated animals of the same strain were noted.

Other findings:

3/10 animls were normal during the whole observation time. All males and 2/5 females chromodacryorrhoea, a sign of general malase, was observed within maximium 4 hr p.a. and is attributed to a reduced wellbeing caused by the dressing. Salivation, noted in one male, is not regarded as important due to single and short occurrence.
8/10 animles were normal at terminal necropsy.
A large spleen, noted in two females, is regarded as incidental finding without toxicological importance.
No sex diffences were noted except for body weight gain which was lowered in some females.

Interpretation of results:

GHS criteria not met

Conclusions:

All animles survived until termination.
No toxicological signs were observed during the test and obervations which were noted were not of toxicological importance.
Therefore LD50 of the test substance was > 2000 mg/kg b.w

Executive summary:

A 50% solution of the test substance was administered once dermally to 5 males and 5 females (Him:OFA rats) (OECD 402).

The test substance was applied at a dose of 2000 mg/kg. the duration of the exposure was 24 hr and the study terminated after 14 days.

All animals survuved until the end of the study.

No toxicological signs were observed during the test and  obervations which were  noted were not of toxicological importance.

Therefore LD50 of the test substance was > 2000 mg/kg b.w

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw