Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Feb-May 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study has been performed according to OECD guideline and is well documented.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Adopted 12 May 1981
GLP compliance:
no
Remarks:
Study undertaken before GLP guidelines were in place
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material: TPAB
- Chemical name: Tetra-n-propylammonium bromide
- CAS no.: 1941-30-6
- Substance type: hygroscopic crystalline powder
- Solubility: water, ethanol
- Melting point: 260-270°C
- Storage condition of test material: at ambient temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa-Credo, Brussels, Belgium
- Age at study initiation: appr. 8 weeks
- Weight at study initiation: males: 356-412 g; females: 214-292 g
- Fasting period before study: yes, overnight before dosing till 5.25 to 6 hours after administration of the test substance
- Housing: individually housed
- Diet: standard laboratory animal diet (Hope Farms, RMH-B, pellet diameter 10 mm), ad libitum
- Water: ad libitum, tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 30-75
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
Dose range finding from: 12-02-1986 to: 20-02-1986
Main test from: 25-03-1986 to: 08-04-1986

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Milli-RO water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg bw
Doses:
1800, 2400 and 3200 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: once every two hours on the day of application, and once every day thereafter
- Frequency of observations and weighing: on the day of dosing, weekly thereafter and at death
- Necropsy of survivors performed: yes
Statistics:
The LD50 value is calculated from the observed mortality data, using the method of Finney (1971).

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
3 900 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Insufficient data to calculate 95% confidence interval.
Sex:
male
Dose descriptor:
LD50
Effect level:
3 300 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Insufficient data to calculate 95% confidence interval.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Insufficient data to calculate 95% confidence interval.
Mortality:
At 1800 mg/kg bw, one male and one female died on day 0, one female died on day 3. No rats exposed to 2400 mg/kg died. At 3200 mg/kg bw, 3 males and 3 females died on day 0. Mortalities on day 0 occurred a few hours after dosing.
Clinical signs:
The female that died 3 days after exposure to 1800 mg/kg bw was found to be lethargic, have breathing problems (gasping), tremors, increased salivation, inflamed eyes, piloerection, bloody nose encrustation and diarrhea.
For the other animals exposed to 1800 mg/kg, only lethargy was reported on the day of exposure (2/4 males; 4/4 females) and day after exposure (2/4 females).
At 2400 mg/kg bw, also lethargy was reported on the day of exposure for 3 males and 2 females, on the following day for 1 female. One male had diarrhea on day 1, bloody nose encrustation was noted for one female on day 1 and 1 male on day 11. On the day of exposure, one female had tremors.
At 3200 mg/kg bw, lethargic behavior was noted for one of the two surviving females on day of exposure, and on day 1 and 3 (one female each). Diarrhea was noted for one male on the day of exposure and one male on day 2 and one female on day 1. Tremors were noted in one female on day 3.
Body weight:
Body weight loss of 10% was recorded for the female that died at 1800 mg/ kg bwon day 3. The weekly group mean body weight gain was normal for the other rats.
Gross pathology:
Macroscopic examination of surviving animals at the end of the study showed no test substance related gross abnormalities.
Macroscopic examination of animals found dead revealed test substance related petechia (1 rat in 1800 mg/kg group) or erosion of the gastro intetsinal tract (2 rats in 1800 mg/kg group and 1 rat in 3200 mg/kg group), followed by bloody content (2 rats in 3200 mg/kg group). Other gross internal findings were aqueous gastrointestinal content (possibly test substance; in 4 animals dosed with 3200 mg/kg), enlarged submaxillary lymphnode (2 rats in 1800 mg/kg group), yellowish discoloured stomach content (1 rat in 1800 mg/kg group), enlarged adrenals and renal hyperemia (1 rat in 1800 mg/kg group and 1 rat in 3200 mg/kg group resp.).

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an oral toxicity test according to OECD 401 with rats, the LD50 was found to be > 2000 mg/kg bw. According to these data, the substance is not classified according to Regulation (EC) No. 1272/2008.
Executive summary:

In an oral toxicity test according to OECD 401, 5 male and 5 female rats were exposed to a single dose of TPAB at 1800, 2400 or 3200 mg/kg. No animals died in the group exposed to 2400 mg/kg bw, in the 1800 mg/kg bw group 3 animals (1male/ 2 females) died and at 3200 mg/kg bw 6 rats died (3 males/ 3 females). Lethargic behaviour was noted for most of the exposed animals, also cases of diarrhea, bloody nose encrustation and occasional tremors were noted. No body weight effect was reported in the surviving animals. Macroscopic examination of surviving animals at the end of the study showed no test substance related gross abnormalities. Macroscopic examination of animals found dead revealed test substance related petechia or erosion of the gastro intestinal tract, followed by bloody content. Other gross internal findings were aqueous gastrointestinal content (possibly test substance; in the majority of animals), enlarged submaxillary lymphnode, yellowish discoloured stomach content, enlarged adrenals and renal hyperemia.

The LD50 for both males and females was found to be 3500 mg/kg bw. Therefore this substance is not classified according to Regulation (EC) No. 1272/2008.