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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
April 13, 2015 - May 26, 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
This endpoint study record is part of a Weight of Evidence approach comprising two acute oral toxicity studies. Both data sources are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tributylmethylammonium chloride
EC Number:
260-135-8
EC Name:
Tributylmethylammonium chloride
Cas Number:
56375-79-2
Molecular formula:
C13H30N.Cl
IUPAC Name:
tributylmethylammonium chloride
Details on test material:
- Name of test material (as cited in study report): Aliquat 175 (Tributylmethylammonium chloride)
- Physical state: solid
- Stability under test conditions: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
- Storage condition of test material: Room temperature
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: AMTBC14001
- Expiration date of the lot/batch: August 22, 2016

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: ca. 10 weeks
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +- 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 3 and 20 g/100 mL
- Amount of vehicle: 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
6 (300 mg/kg) or 3 (2000 mg/kg) female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A check for any dead or moribund animals was made at least once each workday; these records are archived by Bioassay. Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter. Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight, Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations. Necropsy of all animals that died as early as possible after death.
Statistics:
N/A

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
In the single 2000 mg/kg test group two animals died within 1 or 2 hours after administration, respectively.
No mortality occurred in in both 300 mg/kg test groups.
Clinical signs:
In the single 2000 mg/kg bw test group one animal showed impaired general state and piloerection at hour 1 after administration and was found dead at hour 2. A second animal showed poor general state, piloerection, dyspnea, abdominal position and clonic convulsions at hour 0 and was found dead at hour 1 after administration. The surviving single animal in this test group revealed impaired general state and piloerection from hour 0 until day 2, ataxia at hour 0 and 5, cowering position from hour 2 until hour 5 and dyspnea at hour 5.
Clinical signs in the first 300 mg/kg bw test group revealed in all animals impaired general state and piloerection from hour 2 until hour 5 after administration.
The second 300 mg/kg bw test group also showed in all animals impaired general state and piloerection from hour 2 until hour 5 after administration and additionally reduced defecation on study day 1.
Body weight:
The mean body weight of the surviving animals increased within the normal range throughout the study period with two exceptions in the second 300 mg/kg test group. The mean body weights of these animals increased in a normal range during the first observation week, but did not adequately increase during the second week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth.
Gross pathology:
The following macroscopic pathologic findings were observed in the two animals that died in the 2000 mg/kg bw test group:
- Dark red discoloration of the liver
- Bleedings into the glandular stomach
- Red discoloration of the small intestine
There were no macroscopic pathological findings in all animals sacrificed at the end of the observation period (one animal of the 2000 mg/kg bw test group; six animals of both 300 mg/kg bw test groups).

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In an acute oral toxicity study with female rats, performed according to OECD test guidelines and GLP principles, an LD50 >300 <2000 mg/kg bw was determined for MTBAC.
Executive summary:

In an acute oral toxicity study performed with the substance according to OECD TG 423, doses of 2000 and 300 mg/kg bw were administered by gavage to three test groups of three fasted Wistar rats each (2000 mg/kg bw in 3 females and 300 mg/kg bw in 6 females). Mortality was observed in two animals of the 2000 mg/kg bw test group. As substance-related clinical signs poor general state, dyspnea, piloerection, ataxia, cowering position, abdominal position and clonic convulsions were observed at this dose level. Macroscopic pathological findings in the two animals that died were dark red discoloration of the liver, bleedings into the glandular stomach and red discoloration of the small intestine. No mortality occurred at the 300 mg/kg bw dose level. As test-item related clinical signs impaired general state, piloerection and reduced defecation were reported. There were no macroscopic pathological findings in the surviving animals sacrificed at the end of the observation period. The mean body weight of the surviving animals increased within the normal range throughout the study period with two exceptions in the second 300 mg/kg test group. The mean body weights of these animals increased in a normal range during the first week but did not adequately increase during the second week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth. Based on these results the acute oral LD50was calculated to be LD50, oral, rat > 300 < 2000 mg/kg bw.