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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 June 2012 - 08 August 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Esterification products of acrylic acid with reaction products of 2,2-dimethylpropane-1,3-diol and methyloxirane
EC Number:
701-440-2
Molecular formula:
(C3H6O)x (C3H6O)y C11H16O4
IUPAC Name:
Esterification products of acrylic acid with reaction products of 2,2-dimethylpropane-1,3-diol and methyloxirane
Constituent 2
Reference substance name:
Poly [oxy(methyl-1,2 ethanediyl)], a,a'-(2,2-dimethyl-1,3-propanediyl) bis [¿-[(1-oxo-2-propen-1-yl) oxy]-
IUPAC Name:
Poly [oxy(methyl-1,2 ethanediyl)], a,a'-(2,2-dimethyl-1,3-propanediyl) bis [¿-[(1-oxo-2-propen-1-yl) oxy]-
Test material form:
liquid

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 349 g (range: 346 g to 352 g) and the females had a mean body weight of 245 g (range: 237 g to 257 g)
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: the animals were acclimated to the study conditions for a period of 5 (females) or 8 (males) 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: 26 June 2012 to 13 July 2012.

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: at 24h post-exposure, with a moistened cotton pad

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 20 mL/kg
- Constant volume: no.
Duration of exposure:
24 hours
Doses:
2000 mg/kg.
No. of animals per sex per dose:
5 animals per group.
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:
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 or well-defined erythema was noted at application sites of all females and 4/5 males between days 2 and 8, except in one female for which moderate to severe erythe
Gross pathology:
No macroscopic test item-related findings were observed.
The macroscopic findings correlated with common histological findings in control rats, and thus were considered to be incidental.
Other findings:
no

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 as no mortality occured as this dose level.
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 performed according to the international guidelines (OECD No. 402 and Council Regulation No. 440/2008 of 30 May 2008, Part B.3) and in compliance with the principles of Good Laboratory Practice.

 

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

Very slight or well-defined erythema was noted at application sites of females and males between days 2 andsingle female had a more severe erythema on days 2 and 3 a  long with moderate edema and, until day 7, scabs. Various minor degrees of edema (days 2 to 5), dryness (days 3 to 9), and scabs (days 4 to 11) were also observed in a few other females and males.

When compared to CiToxLAB France historical control data, a lower body weight gain was noted in all males and females between day 1 and day 8. Their body weight gain returned to normal thereafter. The body weight of males was not affected by the test item treatment.

No macroscopic test item-related findings were observed.

 

Conclusion

The dermal LD50 of the test item was higher than 2000 mg/kg in rats.

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