N-(1,3-dimethylbutylidene)-5-[(1,3-dimethylbutylidene)amino]-1,3,3-trimethylcyclohexanemethylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 August 2014 - 07 October 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Identificatin: CAS# 71077-09-3
- Batch No.of test material: 76200
- Purity: 98,7%
- Physical state: pale yellow liquid
- Expiration date of the lot/batch: 04 March 2015
- Storage condition of test material: room temperature, in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (approximately 8-12 weeks old)
- Weight at study initiation: 161 to 177 g
- Fasting period before study: overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.
- Housing: Individually housed in polypropylene cages containing woodflakes equipped with water bottles. The room(s) in which the animals were kept were documented in the study records. Each cage was clearly labeled.
- Diet (e.g. ad libitum): Pelleted rodent diet (2014C Teklad Global Rodent diet; Harlan Laboratories) was provided ad libitum throughout the study, except during designated procedures.
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles. Periodic analysis of the water was performed, and results of these analyses are on file at the Test Facility. It is considered that there were no known contaminants in the water that would interfere with the objectives of the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): Fifteen or greater air changes per hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Dose 175mg/kg; concentration 17.5mg/mL; Dose 550mg/kg; concentration 55mg/mL; Dose 2000mg/kg; concentration 200mg/mL
- Justification for choice of vehicle: Arachis oil was used because the test item did not dissolve in distilled water

Doses:

175, 550, 2000 mg/kg body weight

No. of animals per sex per dose:

175 mg/kg body weight; 1 females
550 mg/kg body weight; 2 females
2000 mg/kg body weight; 4 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Postdose observations were performed at periodic intervals on the day of dosing (0.5, 1, 2, 4 hours) and once daily thereafter. Animals were weighed individually on Day 1 (predose), 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross lesions, body weight changes, mortality and other toxicological effects

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

175 mg/kg : 0/1
550 mg/kg: 0/2
2000 mg/kg: 1/4

Clinical signs:

There were no signs of systemic toxicity at 175 mg/kg
Pilo-erection and hunched posture were noted in two animals at a dose level of 550mg/kg
Ataxia and hunched posture were noted in two animals treated at a dose level of 2000mg/kg. Additional signs of systemic toxicity noted in one of these animals were lehargy, ptosis and pilo-erection. No signs of systemic in one animal treated at this does level

Body weight:

The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

Gross pathology:

Hemorrhage and epithelial sloughing of the gastric mucosa was noted at necropsy of the animal treated at a dose level of 2000 mg/kg that died during the study. No abnormatilites were noted at necropsy of animals that were kiled at the end of the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of the test item in rats was established to be 2000 mg/kg body weight.

Executive summary:

The objective of this study was to determine the potential toxicity of the test substance, when given by oral gavage to rats of a single sex at 175, 550 and 2000 mg/kg bw

A toal of seven female animals were dosed individually in sequence with sufficient time (at leas 48h) between each animal, at dose levels ranging from 175 mg/kgbw to 2000 mg/kg bw. The test substance was administered by orally as a solution in arachis oil BP. Animals were subjected to daily observations and weekly determination of body weight.  Macroscopic examination was performed after terminal sacrifice (Day 14). Onme animal treated at a dose level of 2000 mg/kg bw was found dead 4 hours after dosing. The body weight gain shown by the surviving animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value in Wistar rats was estimated to be 2000 mg/kg body weight.

Based on these results, the test substance does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).