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Toxicological information

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:
9 January 1997 to 23 January 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study, to GLP, on closely-related surrogate

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: solid
Details on test material:
- Name of test material (as cited in study report): Tetrammine palladium hydrogen carbonate
- Substance type: No data
- Physical state: pale yellow solid
- Analytical purity: No data
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: No data
- Lot/batch No.: DF0445
- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: ambient temperature, shielded from light

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: 8-12 weeks
- Weight at study initiation: Males-219-244 g; Females-206-236 g
- Fasting period before study: No data
- Housing: Individually during exposure period; groups of five (by sex) for the remainder of the test
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21 deg C
- Humidity (%): 41-55%
- Air changes (per hr): 15/hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light followed by 12 hours continuous dark

IN-LIFE DATES: From: 9 January 1997 To: 23 January 1997

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Shorn skin
- % coverage: 10% of total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage which was further secured with a piece of Blenderm wrapped around each end

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Treated skin and surrounding hair were wiped with cotton wool moistened with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): Not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: Test material was moistened with distilled water prior to use

VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable
Duration of exposure:
24-hour
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Toxicity-0.5, 1, 2 and 4 hours after dosing and subsequently once daily; Weighing-Day 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: erythema and eschar formation, oedema formation
Statistics:
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made

Results and discussion

Preliminary study:
Not applicable
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: CL not applicable
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: CL not applicable
Mortality:
There were no deaths in any of the 10 animals throughout the course of the study
Clinical signs:
No signs of systemic toxicity were noted during the study
Body weight:
All animals showed an expected gain in bodyweight during the study, except for 2 females which showed body weight loss or no gain in bodyweight during the first week and subsequently showed expected gain in bodyweight during the second week
Gross pathology:
No abnormalities were noted at necropsy
Other findings:
- Organ weights: No data
- Histopathology: No data
- Potential target organs: No data
- Other observations: No signs of skin irritation were noted during the study

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In a OECD guideline study, to GLP, the acute dermal LD50 of tetrammine palladium hydrogen carbonate was found to be greater than 2000 mg/kg bw.
Executive summary:

The acute dermal toxicity of tetrammine palladium hydrogen carbonate was evaluated in an OECD Test Guideline 402 study, conducted according to GLP. The test material was applied to the shorn skin of Sprague-Dawley CD rats (5/sex), under a semi-occlusive covering, and removed (by gentle washing) after 24 hr.

There were no signs of systemic toxicity, mortality or pathological findings during the 14-day observation period. Therefore, the acute dermal median lethal dose (LD50) of the test material was found to be greater than 2000 mg/kg bw.