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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 January 2020 - 09 June 2020
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
2017
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Dilithium sebacate
EC Number:
242-999-8
EC Name:
Dilithium sebacate
Cas Number:
19370-86-6
Molecular formula:
C10H16O4.2Li
IUPAC Name:
dilithium sebacate
Test material form:
solid
Details on test material:
- Source and batch number of test material: A050-99-2
- Expiration date of the lot/batch: 11 October 2022
- Purity test date: 11 October 2019
- Storage condition of test material: Room temperature, protected from light
- Treatment of test material prior to testing: Moistened with aqua ad injectionem (1 mL)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 12 - 15 weeks
- Weight at study initiation: 215 - 231 grams
- Fasting period before study: None
- Housing: Individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): Ad libitum to Altromin 1324 maintanence diet
- Water (e.g. ad libitum): Ad libitum to tap water, sulphur acidified to a pH value of 2.8
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
Aqua ad injectionem
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal area of the trunk
- % coverage: 10
- Type of wrap if used: Semi-occlusive dressing made of a porous gauze and non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period the residual test item was removed using aqua ad injectionem (sterile water)
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (corrected for purity of 96%): 389.8 - 465.8 grams
- Constant volume or concentration used: no
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit): 1 mL
- Lot no.: 906243
- Expiry date: 05/2022
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw used in dose range finding test and main test
No. of animals per sex per dose:
1 female (dose range finding test)
2 females (main test)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical examinations were made several times on the day of dosing. Thereafter, the animals were observed for clinical signs of toxicity once daily. The animals were weighed on day 1, 8 and 15.
- Necropsy of survivors performed: yes including macroscopic examinations. In absence of gross pathological changes, no tissues were preserved for a possible histopathological evaluation.
Statistics:
The Fixed Dose Procedure does not require any statistical analysis of the data.

Results and discussion

Preliminary study:
One female was treated with 2000 mg/kg bw in the dose range finding study. No mortality, signs of toxicity or signs of irritation were observed in the female.
Effect levels
Key result
Sex:
female
Dose descriptor:
other: Acute Toxicity Estimate
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs of systemic toxicity were observed. No signs of skin irritation were observed.
Body weight:
No effects on body weight were observed in any animal.
Gross pathology:
No specific gross pathological changes were recorded for any animal.
Other findings:
No other findings were observed.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, single dermal application of the test item Dilithium sebacate to rats at a dose of 2000 mg/kg body weight was associated with no mortality and neither signs of toxicity nor signs of irritation. According to OECD guideline 402, the test item Dilithium sebacate has no obligatory labelling requirement for percutaneous toxicity and is not classified. The Acute Toxicity Estimate was determined to be ATE > 2000 mg Dilithium sebacate / kg body weight, as there was no mortality and neither signs of toxicity nor signs of irritation.
Executive summary:

The acute oral toxicity of Dilithium sebacate to female Wistar rats was determined in a GLP-compliant, fixed-dose method study following OECD guideline 402. A preliminary study indicated no mortality of a single rat at 2000 mg/kg bw Dilithium sebacate, therefore 2000 mg/kg bw was selected for the main study which was conducted on two further animals. Dilithium sebacate was dosed by a single dermal application and the rats were observed for skin irritation, mortality, systemic toxicity and bodyweight gain. No mortality, signs of toxicity or signs of irritation were observed in either of the rats tested. According to OECD guideline 402, the test item Dilithium sebacate has no obligatory labelling requirement for percutaneous toxicity and is not classified. The Acute Toxicity Estimate was determined to be ATE > 2000 mg Dilithium sebacate / kg body weight, as there was no mortality and neither signs of toxicity nor signs of irritation.

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