Reaction mass of copper oxide and manganese dioxide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From Jun. 28, 2006 to Dec. 06, 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 FEB 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

31 JUL 1992

Deviations:

no

GLP compliance:

yes

Remarks:

according to Principles on Good Laboratory Practice (OECD 1997) and TCCA-Good laboratory Practice Standards and Testing Guidelines (Notification No. 2006-04 issued by the National Institute of Environmental Research on Feb. 24, 2006)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Manganese dioxide

EC Number:

215-202-6

EC Name:

Manganese dioxide

Cas Number:

1313-13-9

Molecular formula:

MnO2

IUPAC Name:

Manganese dioxide

Test material form:

solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Supplier: Sigma-Aldrich Co.
- CAS No.: 1313-13-9
- lot/batch No.of test material: 03531AE
- Purity test date: Feb. 2006
- Purity: 99.99%
- Titration: 62% Mn (with KMnO4)
- Trace Analysis (in ppm): Na 45.1, Fe 31.9, Mg 12.3, Ca 5.0, Ag 4.1, Zn 3.8, Cr 1.6
- Apperance: Dark grey powder

VEHICLE
- Mixture of dimethylsulfoxide (DMSO) and sterilized distilled water (35:65, v/v)
- Lot No.: DMSO: DB18472DB/ sterilized distilled water: AAW5AI

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: not specified


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: pulverized test item was suspended and solubilized in vehicle solution
- concentration and homogeneous measurements: not conducted

FORM AS APPLIED IN THE TEST (if different from that of starting material): mixture with vehicle

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Remarks:

Specific Pathogen Free (SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Orient Bio, Ltd.
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at delivery: 7-week old male and 9-week old female rats
- Weight at study initiation: males: 230.7-266.3 g and females: 201.4-229.6 g
- Quarantine and acclimation period: 6 days
- Housing: stainless wire-mesh cage (280W x 500L x 200H mm), 3 and 1 animal during acclimation and test period
- Diet (e.g. ad libitum): pelleted chow ad libitum (supplier: PMI Nutrition International Lot. no: APR 04 063)
- Water (e.g. ad libitum): tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 50±10%
- Air changes (per hr): 10~20 times
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2006-07-07 To: 2006-07-27

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: Mixture of dimethylsulfoxide (DMSO) and sterilized distilled water (35:65, v/v)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal, shaved 24 hours before application
- skin surface: 6 x 8 cm2
- Type of wrap if used: gauze (5 x 7 cm2)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Saline
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3 ml/kg BW according to body weight of animal on treatment day 8callculated with Path/Tox System)
- Constant volume or concentration used: yes

VEHICLE
- Lot/batch no. (if required): DMSO: DB18472DB / sterilized distilled water: AAW5AI

Duration of exposure:

24 hours

Doses:

The dose levels for the study were determined referring to the results of a preliminary study. No toxic signs on mortality, clinical signs, body weight changes and gross findings were at the 500, 1000, and 2000 mg/kg levels of the preliminary study. Therefore a limit dose level of 2000 mg/kg body weight was administered.

No. of animals per sex per dose:

5 animals per sex and dose

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations (clinical signs and mortality): 1, 2, 3, 4, 5, and 6 hours after dosing and once a day from day 2 to day 15
- Frequency of weighing: before test item administration (Day 1) and on Day 2, 5, 8, and 15 after treatment
- Necropsy of survivors performed: yes, with special attention to all vital organs

Statistics:

the study results were analyzed using Path/Tox System (Version 4.2.2, Xybion Medical System Corporation, USA) according to the standard operation procedure of Korea Institute of Toxicology. The value of body weigt was presented by mean ± SD.

Results and discussion

Preliminary study:

No toxic signs on mortality, clinical signs, body weight changes and gross findings were observed in a preliminary study at 500, 1000, and 2000 mg/kg levels of test item.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No unscheduled deaths in any groups during the study period.

Clinical signs:

No abnormal clinical signs were observed in any groups during the study period.

Body weight:

Decreased body weights or suppressed body weight gains were observed on Day 2 in vehicle control group and 2000 mg/kg bw group of both sexes. Observed effects appeared to be caused by the stress given by taping for treatment, since it happened in both control and treatment group.

Gross pathology:

No treatment-related gross findings were observed in all animals.

Any other information on results incl. tables

Tabelle 1: Body weights of rats at day 15.

mg/kg bw	male (n=5)	female (n=5)
0	339.8 ± 23.9	240.5 ± 7.4
2000	340.1 ± 10.8	254.5 ± 20.8

Data are presented as mean ± SD.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Single dermal application of the limit dose of 2000 mg test item per kg bw did not cause lethality in 5 male and 5 female SD rats during the 15 day observation period, resulting in a LD50 > 2000 mg/kg bw.

Executive summary:

To evaluate the acute toxicity after a single dermal administration according to OECD Guideline 402 (limit test) and under GLP, the test item was administered semiocclusively to 2 groups of SD male and female rats (5 animals/group) at doses of 0 and 2000 mg/kg bw. Mortality, clinical signs, body weight changes and gross findings were continually screened for 15 days following the single dose. No treatment-related effects on mortality, clinical signs, body weight changes, and gross findings in SD rats treated with a single dermal dose of test item were observed. Therefore, the LD50 value of the test item was considered to be over 2000 mg/kg bw for both sexes of rats.