Dodecyltrimethylammonium bromide

Endpoint summary

Description of key information

Under the conditions of the present study, the LD50 value for dodecyltrimethylammonium bromide is expected to be between 50 - 300 mg/kg bw after single oral administration in rats (reference 7.2.1-1).

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:

2018-07-31 to 2018-09-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: The mean initial body weight at the start of study was 162 g (range from 152 to 172 g).
- Fasting period before study: Diet was withheld from about 17 to 20 hours before start of treatment until 4 hours after administration.
- Housing: During the acclimation phase, the three rats per treatment group were group-housed in type IV Makrolon® cages with a shelter on softwood bedding material (ABEDD LTE E-001, ABEDD LAB&VET Service GmbH, Austria). Play tunnels (Ref. 14153, Plexx BV, Netherlands) were placed in the cages as additional enrichment. One day before treatment, the rats were single-housed in type III Makrolon"1 cages with a shelter and a play tunnel on softwood bedding material. Wire grids were placed above the softwood granules. They remained in place until all signs of intoxication had subsided. If no signs of intoxication were seen, the wire grids were removed 4 hours after administration. The rats were kept individually until the end of the observation period. The bedding was changed once a week.
- Diet: The rats received a maintenance diet (VI534, ssniff Spezialdiäten GmbH, Germany) ad libitum.
- Water: Drinking water from the community water supply was offered ad libitum in Makrolon® bottles (BIOSCAPE GmbH, Castrop-Rauxel, Germany). Drinking water was changed at least three times per week.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.1 - 23.8 °C
- Humidity (%): 46.8 - 64.0%

Route of administration:

oral: gavage

Vehicle:

other: 0.25% aqueous hydroxypropylcellulose (Methocel® K4M Premium solution, 2.5 g/L distilled water)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5 g/L (50 mg/kg bw test group); 30 g/L (300 mg/kg bw test group)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: Due to the fact, that information concerning the toxic potential of the test item after intravenous administration is available (TSCA Chemical Substance Inventory), the study was started in 3 females with 50 mg/kg body weight.

Doses:

50 and 300 mg/kg bw

No. of animals per sex per dose:

50 mg/kg bw: 6 female rats per dose
300 mg/kg bw: 3 female rats per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
Body weight: All animals were weighed before treatment (day 1) and on day 2, 4, 6, 8, 11, 13 and 15.
Mortality and Clinical Signs: On the day of treatment, each animal was observed for mortality and for symptoms of intoxication at scheduled intervals according to the record sheets. On the following days, the rats were examined once daily. Symptoms were recorded individually for each animal.
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was seen after treatment with 50 mg/kg bw during the course of this study. Two out of three rats treated with 300 mg/kg bw died on day 1 (animal no. 9) and day 2 (animal no. 8), respectively. The third rat (animal no. 7) treated with 300 mg/kg bw was killed in moribund condition on day 4.

Clinical signs:

other: No clinical signs of toxicity were observed after treatment with 50 mg/kg bw. All rats treated with 300 mg/kg bw showed salivation 15 minutes after treatment. Animal no. 8 treated with 300 mg/kg bw showed locomotor disturbance on day 2 and animal no. 7 tr

Gross pathology:

At gross pathology, no abnormalities were detected in those animals that died. Animal no. 7 exhibited a red nodule within the forestomach, caseous content in the intestine and an enlarged mesenteric lymph node.
At histopathology, a severe purulent inflammation with multiple pustules, hemorrhages and ulceration was observed in the forestomach. The intestinal tract showed marked villous atrophy with granulocytic infiltrates, increased single cell necrosis and apical epithelial hypertrophy. In the mesenteric lymph node, a mild sinusoidal edema was seen. Taken together, the test item induced a purulent gastroenteritis, most likely due to local irritative properties.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of the present study, the LD50 value for dodecyltrimethylammonium bromide is expected to be between 50 - 300 mg/kg bw after single oral administration in rats.

Executive summary:

An acute oral toxicity study with the test item, dodecyltrimethylammonium bromide, was performed according to the Acute-Toxic-Class Method and OECD Guideline 423. The study was started with 50 mg/kg in 3 female rats, continued with further 3 females treated with 50 mg/kg bw. Due to the fact, that no mortality was seen after treatment with 50 mg/kg bw, 3 further females were treated with 300 mg/kg bw. Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy.
No mortality was seen after treatment with 50 mg/kg bw during the course of this study. Two out of three rats treated with 300 mg/kg bw died on day 1 (animal no. 9) and day 2 (animal no. 8), respectively. The third rat (animal no. 7) treated with 300 mg/kg bw was killed in moribund condition on day 4. No clinical signs of toxicity were observed after treatment with 50 mg/kg bw. All rats treated with 300 mg/kg bw showed salivation 15 minutes after treatment. Animal no. 8 treated with 300 mg/kg bw showed locomotor disturbance on day 2 and animal no. 7 treated with 300 mg/kg bw showed locomotor disturbance on day 4. The body weight development of all rats treated with 50 mg/kg bw was inconspicuous throughout the study. Animal no. 8 treated with 300 mg/kg bw showed a decrease of body weight on day 2 and animal no. 7 treated with 300 mg/kg bw showed a decrease of body weight on day 4. At gross pathology, no abnormalities were detected in those animals that died. Animal no. 7 exhibited a red nodule within the forestomach, caseous content in the intestine and an enlarged mesenteric lymph node. At histopathology, a severe purulent inflammation with multiple pustules, hemorrhages and ulceration was observed in the forestomach. The intestinal tract showed marked villous atrophy with granulocytic infiltrates, increased single cell necrosis and apical epithelial hypertrophy. In the mesenteric lymph node, a mild sinusoidal edema was seen. Taken together, the test item induced a purulent gastroenteritis, most likely due to local irritative properties.
Under the conditions of the present study, the LD50 value for dodecyltrimethylammonium bromide is expected to be between 50 - 300 mg/kg bw after single oral administration in rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

300 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

An acute oral toxicity study with the test item, dodecyltrimethylammonium bromide, was performed according to the Acute-Toxic-Class Method and OECD Guideline 423 (reference 7.2.1-1). The study was started with 50 mg/kg bw in 3 female rats, continued with further 3 females treated with 50 mg/kg bw. Due to the fact, that no mortality was seen after treatment with 50 mg/kg bw, 3 further females were treated with 300 mg/kg bw. Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy.
No mortality was seen after treatment with 50 mg/kg bw during the course of this study. Two out of three rats treated with 300 mg/kg bw died on day 1 (animal no. 9) and day 2 (animal no. 8), respectively. The third rat (animal no. 7) treated with 300 mg/kg bw was killed in moribund condition on day 4. No clinical signs of toxicity were observed after treatment with 50 mg/kg bw. All rats treated with 300 mg/kg bw showed salivation 15 minutes after treatment. Animal no. 8 treated with 300 mg/kg bw showed locomotor disturbance on day 2 and animal no. 7 treated with 300 mg/kg bw showed locomotor disturbance on day 4. The body weight development of all rats treated with 50 mg/kg bw was inconspicuous throughout the study. Animal no. 8 treated with 300 mg/kg bw showed a decrease of body weight on day 2 and animal no. 7 treated with 300 mg/kg bw showed a decrease of body weight on day 4. At gross pathology, no abnormalities were detected in those animals that died. Animal no. 7 exhibited a red nodule within the forestomach, caseous content in the intestine and an enlarged mesenteric lymph node. At histopathology, a severe purulent inflammation with multiple pustules, hemorrhages and ulceration was observed in the forestomach. The intestinal tract showed marked villous atrophy with granulocytic infiltrates, increased single cell necrosis and apical epithelial hypertrophy. In the mesenteric lymph node, a mild sinusoidal edema was seen. Taken together, the test item induced a purulent gastroenteritis, most likely due to local irritative properties.
Under the conditions of the present study, the LD50 value for dodecyltrimethylammonium bromide is expected to be between 50 - 300 mg/kg bw after single oral administration in rats.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available data are reliable and suitable for classification purposes under Regulation 1272/2008. Based on these data, the substance is considered to be classified for acute oral toxicity (Cat. 3, H301) under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.