Cyclohexanaminium, N,N,N-trimethyl-, sulfate (2:1)

Endpoint summary

Description of key information

LD50(rat): 600 - 2000 mg/kg bw for trimethylcyclohexyl ammonium sulfate, aqueous solution 50 wt.%

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

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: Young adult animals (female animals approx. 10 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Housing: Single housing, Makrolon cage, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase

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

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
For the high dose, the liquid test item was administered undiluted. For the lower dose, an administration volume of 2 mL/kg bw of suitable test item preparations was used to facilitate application. 600 and 300 mg/kg bw: The test item was prepared in deionized water and homogenized for each dose group shortly before and during administration by stirring with a magnetic stirrer.

Doses:

300, 600 and 2000 mg/kg bw (150, 300 and 1000 mg/kg bw acutal dose; to ensure the actual dose, the content of active ingredient (approx. 50%) was taken into account.)

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

> 600 - < 2 000 mg/kg bw

Remarks on result:

other: acutal dose of greater than 300 mg/kg bw and less than 1000 mg/kg bw.

Mortality:

All animals of the 2000 mg/kg bw test group were found dead within 2 or 3 hours after administration. No mortality occurred in both 600 and 300 mg/kg bw test groups.

Clinical signs:

other: In all animals of the 2000 mg/kg bw test group impaired general state was observed at hour 0 and persisted in two of these animals until hour 1 after administration. Thereafter, poor general state was noted in two out of three animals at hour 1 or 2. In t

Gross pathology:

The following macroscopic pathologic findings were observed in the three animals that were found dead in the 2000 mg/kg bw test group: Red discoloration of the glandular stomach and small intestine, swollen glandular stomach and swollen small intestine
There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period (600 mg/kg bw: 6 females, 300 mg/kg bw: 6 females).

Under the conditions of this study the median lethal dose of Trimethylcyclohexylammonium sulfate , aqueous solution 50 wt.% after oral administration was found to be greater than 600 mg/kg bw and less than 2000 mg/kg bw in rats (actual dose of greater than 300 mg/kg bw and less than 1000 mg/kg bw).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Quality of whole database:

GLP guideline study

Additional information

In an acute oral toxicity study performed according to the Acute Toxic Class method, doses of 2000, 600 and 300 mg/kg bw of the test item Trimethylcyclohexylammonium sulfate , aqueous solution 50 wt.% (undiluted or preparations in deionized water) were administered by gavage to five test groups of three fasted Wistar rats each (2000 mg/kg bw in 3 females, 600 mg/kg bw in 6 females, 300 mg/kg bw in 6 females). These doses correspond to actual doses of 1000, 300 and 150 mg/kg bw, taking the content of active ingredient (approx. 50%) into account).

The following test substance-related clinical observations were recorded, clinical signs occurred within 1 day after administration: 2000 mg/kg bw (acutal dose 1000 mg/kg, single group): Mortality in all animals, impaired general state in all animals, poor general state in two animals, dyspnoea in all animals, piloerection in two animals, salivation in all animals, lacrimation in one animal, tremor in two animals, clonic convulsions in two animals, staggering in one animal and abdominal position in all animals. Macroscopic pathologicals findings in the animals that died: Mortality in all animals, impaired general state in all animals, poor general state in two animals, dyspnoea in all animals, piloerection in two animals, salivation in all animals, lacrimation in one animal, tremor in two animals, clonic convulsions in two animals, staggering in one animal and abdominal position in all animals. 600 mg/kg (first and second test group): No mortality occurred, impaired general state in five animals and piloerection in five animals. At the 300 mg/kg (first and second test group) no mortality occurred and no clinical signs were observed. There were no macroscopic pathological findings in the surviving animals sacrificed at the end of the observation period (600 mg/kg bw: 6 females, 300 mg/kg bw: 6 females). The acute oral LD50 was calculated to be LD50, oral, rat > 600 < 2000 mg/kg bw or LD50 oral rat (acutal dose) > 300 < 1000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
only available study

Justification for classification or non-classification

Based on the available studies data on acute toxicity properties the test item is classified and labelled as Xn, R22 according to Directive 67/548/EEC (DSD) and as acute oral harmful cat 4 (H302) according to Regulation (EC) No 1272/2008 (CLP).