Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 April 2013 - 17 June 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

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:
liquid

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: 211 g (range: 192 g to 223 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 May 2013 to 11 June 2013

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 or 200 mg/mL
- Justification for choice of vehicle: as unsatisfactory solubility of the test item was obtained in drinking water treated by reverse osmosis, under similar experimental conditions (i.e. heterogeneous emulsion at the concentration of 200 mg/mL was obtained), another vehicle was chosen from the following organic solvents (in order of preference): 0.5% methylcellulose aqueous solution and corn oil. A solution was obtained at the concentration of 200 mg/mL in corn oil.
- Maximum dose-volume applied: 10 mL/kg

DOSAGE PREPARATION : 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 :
- Rationale for the selection of the starting dose: since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data were taken into account by the Sponsor, the starting dose-level was 300 mg/kg for ethical reasons.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
nulliparous and non-pregnant females.
300 mg/kg : 3 females
2000 mg/kg: 3 + 3 females
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: the day of group allocation, 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:
No clinical signs were observed in any animals.
Body weight:
The mean body weights and mean body weight changes (g) recorded in test item-treated animals during the observation period and in CiToxLAB France historical control data are summarized in the Table 1.
Body weight was unaffected by the test item treatment, when compared to historical control data.
Gross pathology:
There were no findings considered to be related to the test item administration.
The few macroscopic findings noted at the end of the observation period (dilatation of the uterus, brown discoloration of the lungs) were of those commonly recorded in the rat and none were considered to be related to the test item administration.
Other findings:
no

Any other information on results incl. tables

Table 1

 

Sex

Female

Group

Historical control data

1

2

3

Dose-level (mg/kg)

0

300

2000

2000

Body weight (mean (± SD))

 

 

 

 

. Day 1

208 (± 11.7)

219 (± 4.5)

214 (± 1.5)

199 (± 7.0)

. Day 8

246 (± 12.7)

257 (± 4.7)

256 (± 8.5)

243 (± 8.7)

. Day 15

266 (± 14.0)

281 (± 5.8)

280 (± 3.8)

256 (± 9.6)

Body weight change (mean (± SD))

 

 

 

 

. Days 1-8

+39 (± 5.1)

+39 (± 6.0)

+41 (± 9.6)

+44 (± 4.0)

. Days 8-15

+20 (± 6.3)

+24 (± 8.0)

+24 (± 8.7)

+13(± 2.1)

. Days 1-15

+58 (± 5.8)

+62 (± 2.6)

+65 (± 5.1)

+57 (± 5.8)

SD: standard deviations.

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the oral LD50 of 1,10-decanediol diacrylate was higher than 2000 mg/kg in rats.

Executive summary:

The objective of this study was to evaluate the potential acute toxicity of 1,10-decanediol diacrylate 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 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.

Body weight gain was unaffected by the test item treatment, when compared to historical control data.

The test item administration did not induce any macroscopic findings at necropsy.

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 CLP Regulation.