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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 June 2013 - 06 August 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
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
see below
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Principles of method if other than guideline:
The study was performed in accordance with study plan No. 40081 TAR and subsequent amendment, with the following deviations from the agreed study plan:
. on day 1, females were observed during the first 5 hours after treatment for the recording of the clinical signs, instead of during the first 4 hours after treatment
These deviations were considered not to have compromised the validity or integrity of the study.
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3-methyl-1,5-pentanediyl diacrylate
EC Number:
264-727-7
EC Name:
3-methyl-1,5-pentanediyl diacrylate
Cas Number:
64194-22-5
Molecular formula:
C12H18O4
IUPAC Name:
3-methyl-5-(prop-2-enoyloxy)pentyl prop-2-enoate

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system 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 314 g (range: 304 g to 325 g) and the females 201 g (range: 197 g to 208 g).
- Housing: the animals were housed by five from the same sex and group in 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: a period of 5 days before treatment.

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: 09 July 2013 to 26 July 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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.905 mL/kg
- Constant volume: no
- For solids, paste formed: no
Duration of exposure:
one single exposure
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 animals per sex per dose
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

Preliminary study:
no
Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No unscheduled deaths occurred during the study.

Clinical signs:
other: No clinical signs indicative of systemic toxicity were observed in any animals. Very slight to severe erythema was noted on the application sites of males and females, from day 2 up to day 11 at the latest. Very slight to moderate dryness was observed on
Gross pathology:
There were no test item-related changes at necropsy.
Diffuse red discoloration of the left thymic lobe was observed in one female given 2000 mg/kg. As this observation is commonly seen in the rat, any relationship with the test item was excluded.
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)

201 (± 4.8)

362 (± 12.0)

314 (± 8.5)

. Day 8

253 (± 12.0)

215 (± 3.9)

394 (± 15.3)

343 (± 17.2)

. Day 15

273 (± 16.3)

232 (± 4.1)

441 (± 21.5)

389 (± 19.8)

Body weight change (mean (± SD))

 

 

 

 

. Days 1-8

+17 (± 11.0)

+13 (± 5.5)

+32 (± 9.1)

+28 (± 11.1)

. Days 8-15

+20 (± 7.1)

+17 (± 6.2)

+47 (± 7.5)

+46 (± 4.5)

. Days 1-15

+37 (± 16.3)

+31 (± 6.0)

+79 (± 15.6)

+75 (± 12.2)

SD: standard deviations.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 of the test item was higher than 2000 mg/kg in rats.
Executive summary:

The objective of this study was to evaluate the potential toxicity of the test item following a single dermal application to rats.

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

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 reportas no microscopic examination was performed.

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

Very slight to severe erythema was noted on the application sitesof males and females, from day 2 up to day 11 at the latest. Very slight to moderate dryness was observed on the application sites from day 5 to days 15 at the latest for females and 13 at the latest for males. Scabs on the application site were noted in 3/5 males and 3/5 females starting on day 5, 6 or 8, and up to day 11 at the latest.

These erythema, scabs and dryness were considered test item-related.

Body weight of animals was unaffected by the test item treatment when compared to CiToxLAB France historical control data.

There were no test item-related changes at necropsy.

Fourteen days following a single dermal application of test item at the dose-level of 2000 mg/kg to rats, no test item-related changes were seen at necropsy. The dermal LD50 of the test item was higher than 2000 mg/kg in rats.