Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 April 2013 - 13 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 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/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: the males had a mean body weight of 352 g (range: 340 g to 361 g) and the females had a mean body weight of 233 g (range: 223 g to 243 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: 21 May 2013 to 07 June 2013

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% of body surface, dorsal site
- Type of wrap if used: hydrophilic gauze pad + adhesive hypoallergenic aerated semi-occlusive dressing + restraining bandage

REMOVAL OF TEST SUBSTANCE
- Removal of dressing: 24h post-exposure
- Washing: none

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume: no
Duration of exposure:
24h
Doses:
2000 mg/kg
No. of animals per sex per dose:
ten rats (five males and five nulliparous and non pregnant 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 on 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:
male/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:
Chromodacryorrhea was observed in 1/5 males on days 7 and 8. As this clinical sign was of isolated occurrence, this was considered as incidental.
Erythema (very slight to severe) and edema (very slight or slight) were noted on application site of all male and female animals from day 2 up to day 7 at the latest.
These findings were associated with dryness of the skin (very slight or slight) at application site of all males and at application site of 4/5 females from day 4 up to day 15 at the latest.
In addition, desquamation was noted in 2/5 females from day 4 to day 13 or 14.
Scabs on application site were also observed in 1/5 males and 1/5 females between day 5 and day 7.
Body weight:
The mean body weights and the mean body weight changes (g) recorded in test item-treated animals during the observation period and in historical control data are summarized in the Table 1.
Body weight of animals 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 treatment period (deformation and strangling of the spleen in a single male at 2000 mg/kg) were considered to be fortuitous.
Other findings:
no

Any other information on results incl. tables

Table 1. 

Sex

Female

Male

Group

historical control data

1

historical control data

2

Dose-level (mg/kg)

0

2000

0

2000

Body weight (mean (± SD))

 

 

 

 

. Day 1

236 (± 8.9)

233 (± 8.1)

362 (± 12.0)

352 (± 7.9)

. Day 8

253 (± 12.0)

250 (± 8.2)

394 (± 15.3)

383 (± 9.6)

. Day 15

273 (± 16.3)

275 (± 8.4)

441 (± 21.5)

430 (± 14.9)

Body weight change (mean (± SD))

 

 

 

 

. Days 1-8

+17 (± 11.0)

+18 (± 8.6)

+32 (± 9.1)

+31 (± 3.6)

. Days 8-15

+20 (± 7.1)

+25 (± 2.8)

+47 (± 7.5)

+47 (± 7.2)

. Days 1-15

+37 (± 16.3)

+42 (± 6.5)

+79 (± 15.6)

+78 (± 9.5)

SD: standard deviations.

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the dermal LD50 of 1,10-decanediol diacrylate was higher than 2000 mg/kg in rats.
Therefore, the test item should not be classified as harmful or toxic by dermal route according to the criteria of CLP Regulation.
Executive summary:

The objective of this study was to evaluate the potential toxicity of 1,10-decanediol diacrylate following a single dermal application to rats.

This study was conducted in compliance with OECD Guideline No. 402 and the principles of Good Laboratory Practices.

Methods

The test item was applied in its original form to the skin of five female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi-occlusive dressing for 24 hours.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. From day 2, any local reactions at the treatment site were also noted. 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.

No clinical signs indicative of systemic toxicity were observed in any animals.

 

Erythema and edema were noted on application site of all male and female animals from day 2 up to day 7 at the latest. These findings were associated with dryness of the skin at application site of all males and at application site of 4/5 females from day 4 up to day 15 at the latest.

In addition, desquamation was noted in 2/5 females from day 4 to day 13 or 14.

Scabs on application site were also observed in 1/5 males and 1/5 females between day 5 and day 7.

Body weight of animals 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 dermal LD50 of 1,10-decanediol diacrylate was higher than 2000 mg/kg in rats.

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