Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
This study was conducted between 26 October 2016 and 05 December 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Reliability 1 is assigned because the study was conducted according to OECD TG 423 in compliance with GLP, without deviations that influence the quality of the results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(2,4-dimethylcyclohex-3-en-1-yl)propan-1-ol
EC Number:
944-553-4
Cas Number:
1632042-40-0
Molecular formula:
C11H20O
IUPAC Name:
1-(2,4-dimethylcyclohex-3-en-1-yl)propan-1-ol
Test material form:
solid
Details on test material:
- Substance name as cited in test report: FRET 11-0571
- Phystical state: white solid
- Storage conditions: ambient temperature (15-25 °C)
Specific details on test material used for the study:
Identification: FRET 11-0571
Physical state/Appearance: white solid
Storage Conditions: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK.
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: The body weight variation did not exceed ±20% of the mean body weight at the start of treatment.
- Fasting period before study: overnight fast immediately before dosing
- Housing: The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet and water: With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Remarks:
Dimethyl sulphoxide was used because the test item did not dissolve/suspend in distilled water or arachis oil BP.
Details on oral exposure:
In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.

Groups of fasted animals were treated as follows:

Dose level: 300 mg/kg
Concentration: 30 mg/ml
Dose volume: 10 ml/kg
Number of rats: 1 (female)

In the absence of toxicity at a dose level of 300 mg/kg, an additional animal, followed by an additional group of 4 animals were treated as follows:

Dose level: 2000 mg/kg
Concentration: 200 mg/ml
Dose volume: 10 ml/kg
Number of rats: 5 (female)

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
1 females at 300 mg/kg
5 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days.
Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes. At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Dose Level - 300 mg/kg: No signs of systemic toxicity were noted during the observation period.
Dose Level - 2000 mg/kg: No signs of systemic toxicity were noted in the initial treated animal during the observation period.
Signs of systemic toxicity noted in the four additional treated animals were hunched posture, ataxia, tiptoe gait, labored respiration and/or decreased respiratory rate, pilo erection, dehydration, loss of righting reflex and lethargy. These four animals appeared normal 3 days after dosing.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified according to CLP based on OECD TG No.423 study
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.
Executive summary:

Acute oral toxicity: In this study (conducted to OECD TG No.423), 1 rat (female) was administered the substance at dose level of 300 mg/kg bw and 5 rats (female: one individual initially, followed by a group of 4) were administered the substance at dose level of 2000 mg/kg bw.

The rat at 300 mg/kg bw showed no mortality, no clinical signs, expected gains in body weight, no abnormalities at necropsy.

The rats at 2000 mg/kg bw showed no mortality, expected gains in body weight, no abnormalities at necropsy. The initial treated animal showed no clinical signs. The four additional treated animals showed signs of systemic toxicity: hunched posture, ataxia, tiptoe gait, labored respiration and/or decreased respiratory rate, pilo erection, dehydration, loss of righting reflex and lethargy.  These four animals appeared normal 3 days after dosing.  

The calculated acute oral LD50 for females was estimated to be greater than 2000 mg/kg bw.