Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 to 30 March 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary GLP guideline-compliant study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

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
Remarks:
OECD; self-certified
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Succinic anhydride (trade name Bernsteinsäureanhydrid) was supplied by the Sponsor on 29 October 2009. Batch no: LEBA5A3070. Described as a white powder/ colourless solid. The material was stored at room temperature, with an expiry date of 30 March 2010.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
The animals were male and female Crl:CD(SD) rats, obtained from Charles River Deutschland GmbH. Females were nulliparous and non-pregnant. The males were approximately 8 weeks old and the females were approximately 12 weeks old at the time of administration. The rats were acclimatised for at least 7 days.A health inspection was performed prior to commencement of the study to ensure that the animals were in good health. Special attention was paid to the skin, which was confirmed to be intact and free from any abnormality. Room temperature ranged from 19.96 to 20.99°C. Relative humidity ranged from 45.08 to 58.78%. There were 12 air changes per hour, and artificial light was provided on a 12 hour light/dark cycle. The rats were housed singly in Makrolon type III cages with wire mesh lids. Autoclaved Aspen wood chips were provided as bedding. Nibbling wood bricks and nesting material from the same material and source as the bedding material were also provided. Ssniff R/M-H maintenance diet for rats and mice was provided ad libitum (Ssniff Spezialdiäten GmbH, Germany). Tap water was provided ad libitum. Individuals were identified with felt-tipped pen on the tails.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
A single dermal administration was performed by applying the test substance to an area of least 10% of the estimated body surface. The test site was located on the dorsal thoracic region. An area of 6.5 cm x 8 cm (52 cm²) was marked.The hair of the dorsal trunk was clipped with an electric hair clipper one day before test substance application. Test substance amounts were calculated and weighed for each rat using individual body weights determined on the day of administration.A cellulose patch (Pehazell, Hartmann AG) with the correct amount of test substance on the surface and soaked in corn oil (to get optimal contact with the skin) was applied to the test site and held in place with non-irritating tape (Blenderm 3M). The test site was covered by a semi-occlusive dressing (Fixomull Stretch).At the end of the exposure period the dressing, the tape and the patch were removed. Residual test substance was wiped off using wet cellulose tissue, if necessary.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 rats/sex
Control animals:
not required
Details on study design:
Observations were performed 0-0.5, >0.5-1, >1-2, >2-4 and >4-6 hours after administration, then at least once daily for a total of 2 weeks. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions. Body weights were determined immediately prior to administration, then 7 and 14 days after administration. All animals were sacrificed at the end of the observation period by CO2 inhalation and subjected to a necropsy including a gross pathological examination.
Statistics:
Formal statistical analysis was not required.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs were observed in any animal during the observation period.
Body weight:
All rats gained weight in the first and second week of the observation period.
Gross pathology:
No abnormalities were detected at necropsy.
Other findings:
3/5 males and all females exhibited erythema and eschar formation at the application site. These local effects were observed 1 day after administration lasting until a maximum of 7 days post administration.

Any other information on results incl. tables

The acute dermal LD50 of succinic anhydride is greater than 2000 mg/kg bw in rats. Comparison of the dermal toxicity results for succinic and maleic anhydrides, suggest that succinic anhydrides is less toxic than other anhydrides.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 of succinic anhydride is greater than 2000 mg/kg bw in rats.
Executive summary:

The acute dermal toxicity of succinic anhydride was determined in rats, according to OECD test method 402. The test substance was administered once to the shaved dorsal skin of 5 male and 5 female Sprague-Dawley rats at a dose of 2000 mg/kg bw. The test site was covered by a semi-occlusive dressing, held in place for 24 hours. The rats were observed for 14 days.

There were no effects on body weight; all animals gained weight during the observation period. No systemic signs of toxicity were noted, however local irritation at the test site (erythema and eschar formation) were observed 1 to 7 days after administration. No abnormalities were detected at necropsy.

It was therefore concluded that the acute dermal LD50 of succinic anhydride is greater than 2000 mg/kg bw in rats.