Tricyclo[3.3.1.13,7]decan-1-aminium, N,N,N-trimethyl-, hydroxide (1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

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 (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tricyclo[3.3.1.13,7]decan-1-aminium, N,N,N-trimethyl-, hydroxide (1:1)

EC Number:

610-954-5

Cas Number:

53075-09-5

Molecular formula:

C13 H25 N O

IUPAC Name:

Tricyclo[3.3.1.13,7]decan-1-aminium, N,N,N-trimethyl-, hydroxide (1:1)

Details on test material:

- Name of test substance: Adamantyltrimethylammoniumhydroxid 20%
- Batch identification: ADTAOH 20%
- CAS No.: 53075-09-5
- Purity: 20.1 g/100g
- Homogeneity: The test substance was homogeneous by visual inspection.
- Storage conditions: Room temperature/ under N2
- Physical state/ color: Liquid/ colorless, clear
- Density [g/mL]: 1.040 (determined by Bioassay)

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
- Age at study initiation: Young adult animals (female animals approx. 10 – 11 weeks)
- Sex: As suggested by the OECD guideline nulliparous and non-pregnant female animals were used for the test, because there is no indication that male animals are likely to be more sensitive to the acute effects of the test substance.
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study:
- Housing: Single housing in Makrolon cages, type III
- Diet: VRF1(P); SDS Special Diets Services, Altrip, Germany
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 20-80
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

FORM OF ADMINISTRATION:
2000 mg/kg bw group: Undiluted (no vehicle)
300 mg/kg bw: Solution in doubly distilled water

VEHICLE
- Concentration in vehicle: 300 mg/kg bw group: 15 g/100 ml
- Justification for choice of vehicle: Aqueous formulation corresponds to the physiological medium.

MAXIMUM DOSE VOLUME APPLIED:
2 ml/kg bw

DOSAGE PREPARATION:
The test-substance preparations of the 300 mg/kg bw test groups were produced shortly before the administrations by stirring with a magnetic stirrer.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

2000 mg/kg bw group: 3 females
300 mg/kg bw group: 2 x 3 females

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 animal was made twice each workday and once on weekends and on public holidays. Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals. Recording of individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Additionally, at day of death in animal which was sacrificed moribund on study day 8.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal of the 2000 mg/kg test group was found dead at hour 1 and one animal was sacrificed in a moribund state on study day 8.
No mortality occurred in the 300 mg/kg administration groups.

Clinical signs:

other: Clinical observation in the 2000 mg/kg body weight test group revealed impaired general state, dyspnea, salivation, piloerection, exsiccosis, gasping, twitching, clonic convulsions, reduced and non feces. Findings were observed from hour 0 through to stud

Gross pathology:

At necropsy the animals of the 2000 mg/kg test group which died or were sacrificed in a moribund state showed red discoloration of the lung, red to brown discolored content of the stomach, rigidity of the stomach wall covered with mucus, areal bleeding of the glandular stomach. Furthermore light red spotted discoloration of the liver and red discoloration of the small intestine was recorded. No macroscopic pathologic abnormalities were noted in the surviving animals examined on the last day of observation (2000 mg/kg bw: 1 female; 300 mg/kg bw: 6 females).

Any other information on results incl. tables

Mortality data:

Dose (mg/kg bw)	2000	300	300
Sex	female	female	female
Administration	1	1	2
No. of animals	3	3	3
Mortality (animals)	2	No mortality	No mortality

 

Individual body weight changes:

Dose (mg/kg bw)	2000				300				300
Administration	1				1				2
Animal No.	1	2	3	mean	1	2	3	mean	1	2	3	mean
Body weight at study day (g)
0	173	188	173	178	196	201	186	194	190	180	163	178
7	180	148	+	164	214	218	201	211	199	186	168	184
8	+	147*	+	+	+	+	+	+	+	+	+	+
14	185	+	+	185	221	218	202	214	205	186	174	188

+: no further data; *: weight at death

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study the median lethal dose of Adamantyltrimethylammoniumhydroxid 20% after oral administration was found to be greater than 300 mg/kg and less than 2000 mg/kg body weight in rats.

Executive summary:

The study was performed according to OECD guideline 423 in compliance with GLP to assess the acute toxicity following oral administration of Adamantyltrimethylammoniumhydroxid 20% in Wistar rats.

Single doses of 2000 and 300 mg/kg body weight of the test material or test material preparations in doubly distilled water were given to three test groups of three fasted female animals each, (2000 mg/kg bw in 3 females, 300 mg/kg bw in 6 females) by gavage in a sequential manner.

One animal of the 2000 mg/kg test group was found dead at hour 1 and one animal was sacrificed in a moribund state on study day 8. No mortality occurred in the 300 mg/kg administration groups. Clinical observation in the 2000 mg/kg body weight test group revealed impaired general state, dyspnea, gasping, salivation, piloerection, exsiccosis, twitching, clonic convulsions, reduced and non feces. Findings were observed from hour 0 through to study day 8 after administration. No clinical signs and findings were observed in the 300 mg/kg test groups. The mean body weight of the 2000 mg/kg body weight administration group decreased in the first exposure week, but increased during the second exposure week. This effect was observed because the moribund sacrificed animal showed a marked loss of body weight. The mean body weights of the test 300 mg/kg groups increased normally throughout the study period. At necropsy the animals of the 2000 mg/kg test group which died or were sacrificed in a moribund state showed red discoloration of the lung, red to brown discolored content of the stomach, rigidity of the stomach wall covered with mucus, areal bleeding of the glandular stomach. Light red spotted discoloration of the liver, red discoloration of the small intestine. No macroscopic pathologic abnormalities were noted in the surviving animals examined on the last day of observation (2000 mg/kg bw: 1 female; 300 mg/kg bw: 6 females).

Under the conditions of this study the LD50 of Adamantyltrimethylammoniumhydroxid 20% after oral administration was found to be greater than 300 mg/kg and less than 2000 mg/kg body weight in rats.