Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 January 2014 -- 26 March 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guidelines; adequate consistence between data, comments and conclusions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: colorless liquid
Details on test material:
- Name of test material: Tricyclodecane dimethanol diacrylate
- Physical state: colorless liquid
- Storage conditions: at room temperature and protected from light

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: 209 g (range: 194 g to 234 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: 24 February 2014 to 26 March 2014

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: following recommendation from the Sponsor, the solubility assay first started at the concentration of 200 mg/mL, and following indication on the test article description, the choice vehicle was 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 and protected from light prior to administration.



CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: ----
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
Three nulliparous and non-pregnant female rats
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
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 other: mg/kg
Based on:
test mat.
Remarks on result:
other: no mortality
Mortality:
No unscheduled deaths occurred during the study.
Clinical signs:
No clinical signs were observed in any animals.
Body weight:
When compared to CiToxLAB France historical control data, a lower body weight gain was noted in 2/6 females (groups 2 and group 3) given 2000 mg/kg (+7 g vs. +20 g ± 6.7 g in control data base) between Day 8 and Day 15. A higher body weight gain was observed in one female (group 3) (+30 g vs. +20 g ± 6.7 g in control data base) given 2000 mg/kg over the same period.
Nevertheless, compared to CiToxLAB France historical control data, the body weight of the animals was considered to be unaffected by the test item treatment. (see Table 1)
Gross pathology:
There were no test item-related macroscopic post-mortem findings.
The few gross abnormalities were considered to be part of the normal background in untreated rats of these strain and age.
Other findings:
no

Any other information on results incl. tables

 Table 1

Sex

Female

Group

CiToxLAB France historical control data

1

2

3

Dose-level (mg/kg)

0

300

2000

2000

Body weight (mean (± SD))

 

 

 

 

. Day 1

198 (± 6.6)

201 (± 6.2)

224 (± 13.2)

201 (± 5.3)

. Day 8

239 (± 8.6)

246 (± 10.0)

273 (± 13.7)

242 (± 9.5)

. Day 15

258 (± 8.6)

262 (± 8.7)

285 (± 14.0)

261 (± 20.0)

Body weight change (mean (± SD))

 

 

 

 

. Days 1-8

+41 (± 7.2)

+45 (± 6.1)

+48 (± 0.6)

+41 (± 4.7)

. Days 8-15

+20 (± 6.7)

+16 (± 2.5)

+12 (± 4.7)

+19 (± 11.5)

. Days 1-15

+60 (± 6.0)

+61 (± 4.4)

+61 (± 4.0)

+60 (± 14.7)

SD: standard deviations.

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP Regulation
Conclusions:
Under the experimental conditions of this study, the oral LD50 of the test item, was higher than 2000 mg/kg in rats.
Therefore, the test item should not be classified as harmful or toxic by oral route according to the criteria of the CLP Regulation.
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 OECD Guideline No. 423 and the principles of Good Laboratory Practices.

Methods

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

Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data have been taken into account by the Sponsor, the starting dose-level 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 higher dose-level, the results were confirmed in other three 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. Macroscopic lesions were preserved in buffered formalin then destroyed at the finalization of the study report as no microscopic examination was performed.

Results

No unscheduled deaths occurred during the study and no clinical signs were observed in any animals.

When compared to the historical control data, a lower body weight gain was noted in 2/6 females given 2000 mg/kg (+7 gvs.+20 g ± 6.7 g in control data base) between Day 8 and Day 15. A higher body weight gain was observed in 1/6 females (+30 g vs.+20 g ± 6.7 g in control data base) given 2000 mg/kg over the same period.

Nevertheless, compared to the historical control data, the body weight of the animals was considered to be unaffected by the test item treatment.

No test item-related macroscopic post-mortem findings were noted.

Conclusion

Under the experimental conditions of this study, the oral LD50 of the test item, was higher than 2000 mg/kg in rats.

Therefore, the test item should not be classified as harmful or toxic by oral route according to the criteria of the CLP Regulation.