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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 November 2015 -- 13 January 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (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

Constituent 1
Chemical structure
Reference substance name:
3,3,5-trimethylcyclohexyl acrylate
EC Number:
289-200-9
EC Name:
3,3,5-trimethylcyclohexyl acrylate
Cas Number:
86178-38-3
Molecular formula:
C12H20O2
IUPAC Name:
3,3,5-trimethylcyclohexyl prop-2-enoate
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France.
- Age/Weight: on the day of treatment, the females were 8 weeks old and had a mean body weight of 216 g (range: 198 g to 235 g).
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 14 December 2015 to 13 January 2016

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: in the absence of recommendation from the Sponsor, the solubility assay first started at the concentration of 200 mg/mL, and the first choice vehicle was drinking water treated by reverse osmosis.
As unsatisfactory solubility of the test item was obtained in this vehicle (i.e. heterogeneous emulsion at the concentration of 200 mg/mL), another vehicle was chosen from the following organic solvents (in order of preference): 0.5% methylcellulose aqueous solution and corn oil.

- Maximum dose-volume applied: 10 mL/kg

DOSAGE PREPARATION (if unusual): fresh dose formulations were prepared by the CiToxLAB France Pharmacy on the day of each administration and kept at room temperature prior to administration.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: 300 mg/kg
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
Three nulliparous and non-pregnant female per treatment step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).
Statistics:
no

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No unscheduled deaths occurred during the study.

Clinical signs:
At 300 mg/kg, no clinical signs were observed in any animals.
At 2000 mg/kg, hypoactivity, staggering gait and half-closed eyes were observed on Day 1 approximately 6 hours after treatment in 3/6 females, while another 1/6 females showed ptyalism on Day 1, 30 minutes after treatment and a slight alopecia on both forelimbs from Day 14. No clinical signs were noted in the remaining 2/6 females treated at the same dose-level.
Body weight:
At 300 mg/kg, lower mean body weight gain was noted between Day 1 and Day 8, when compared to CiToxLAB France historical control data (+38 g vs. +46 g in control data base). This was followed by higher mean body weight gain between Day 8 and Day 15 (+16 vs. +10 g in control data base). Therefore no relevant differences from CiToxLAB France historical control data were noted in the mean body weight change of test item-treated animals over the study period.

Compared to CiToxLAB France historical control data, the mean body weight of the animals was considered to be unaffected by the test item treatment.
Gross pathology:
There were no macroscopic findings at necropsy.
Other findings:
no

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the oral LD0 of the test item was higher than 2000 mg/kg in rats.
Executive summary:

The objective of this study was to evaluate the potential acute toxicity of the test item following a single oral administration (gavage) to rats.

This study was conducted in compliance with the OECD Guideline No. 423 and the principles of Good Laboratory Practice.

 

Methods

 

The test item was administered once by the oral route (gavage) to three groups of three fasted female Sprague-Dawley rats with a dosage-volume of 10 mL/kg. The test item was prepared in corn oil.

No relevant toxicity data were available for estimation of a lethal selected dose-level. The starting dose-level selected was 300 mg/kg for ethical reasons. After the first assay, the next higher dose-level of 2000 mg/kg was tested. Then, as no toxicity was observed at this dose-level, the results were confirmed in three additional females.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on Day 1 and then on Days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No tissues were preserved.

 

Results

 

No unscheduled deaths occurred during the study.

At 300 mg/kg, no clinical signs were observed in any animals.

At 2000 mg/kg, hypoactivity, staggering gait and half-closed eyes were observed on Day 1 approximately 6 hours after treatment in 3/6 females, while another 1/6 females had ptyalism on Day 1, 30 minutes after treatment and slight alopecia on both forelimbs from Day 14. No clinical signs were noted in the remaining 2/6 females treated at the same dose-level.

No relevant differences from historical control data were noted in the body weight change and body weight of test item-treated animals over the study period.

There were no macroscopic findings at necropsy.

Conclusion

Under the experimental conditions of this study, the oral LD0 of the test item was higher than 2000 mg/kg in rats.

Therefore, the test item should not be classified regarding its toxic potential by oral route according to the criteria of CLP Regulation.

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