Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-01-24 to 2011-02-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant

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:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
Regulation (EC) 440/2008 of 30 May 2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
other: Crl(WI)Br
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90.
- Age at study initiation: Young adult rats, femles were nulliparous and non-pregnant
- Weight at study initiation: Preliminary study: 202-222 g, Male 274-300 g, Female 220-244 g
- Fasting period before study: food but not water was withheld overnight
- Housing: during acclimatisation: 3 animals/sex/cage, during the study: individually
- Diet: ad libitum (ssniff® SM R/M-Z+H complete diet )
- Water: ad libitum
- Acclimation period: 5 days for the pre-study, 20 days for the main study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 8-12 air exchanges/hour by central air-condition system.
- Photoperiod: Artificial light, from 6 a.m. to 6 p.m.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: at least 10 % of the total body surface
- Type of wrap if used: sterile gauze pad below a semi-occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: water pre-warmed to body temperature
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: Main-tests: 2000 mg/kg bw; pre-test: Pre-test: 5 mg/kg bw, 50 mg/kg bw, 300 mg/kg bw, 2000 mg/kg bw
- Constant volume or concentration used: yes
Duration of exposure:
single administration for 24 hours
Doses:
Main-test
2000 mg/kg bw
No. of animals per sex per dose:
Main-test: 5 males and 5 females
Pre-tests: 2 females per dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: For the main study, the body weight of all animals were recorded on day 0 (shortly before the treatment), on day 7 and on day 15 (with a precision of 1 g)
- Necropsy of survivors performed: yes
- Other examinations performed: Animals were observed individually 1 h and 5 h after dosing, and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
All animals were subjected to gross pathology. All animals were exsanguinated under isoflurane anaesthesia. After examination of the external appearance the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross pathological changes were recorded for each animal on the post mortem record sheets. The animals of preliminary study were humanely sacrificed on day 7.
Statistics:
not applicable

Results and discussion

Preliminary study:
No mortalities occured during the preliminary study
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities occured
Clinical signs:
In one male treated with 2000 mg/kg bw dose porphyrin excretion (1 cases of 80 observations) was observed. This symptom (score +1) was found on right eye on Day 1. Four animals were free of symptoms during the study. All male animals were free of symptoms on Day 0 and between Day 2 and Day 14.
In one female treated with 2000 mg/kg bw dose blood around the nose (2 cases of 80 observations; score +2) was observed. It was detected on Day 0 between 1 and 5 hours after the treatment. Four animals were free of symptoms during the study. All female animals were free of symptoms between Day 1 and Day 14.

No systemic toxic clinical signs were observed. The general symptoms observed could not be connected to a toxic effect of the test item but may be related to the induced stress during the treatment procedure (for example due to the presence of the bandage etc.).

No local symptoms (dermal irritation in form of redness and oedema) were observed on the treated skin of animals.
Body weight:
The mean body weight of the male animals corresponded to their species and age throughout the study.
A body weight loss was observed in two females treated with 2000 mg/kg bw Cesiumiodid 99.999 between Day 0 and Day 7. This body weight loss was very low (approx. 1.3 and 2.0 %, respectively) and the animal´s body weight exceeded the original body weight by the end of study. Thus, this effect can be interpreted as an individual variation without toxicological meaning.
Gross pathology:
All animals survived until the scheduled necropsy on Day 15.
No macroscopic alterations due to the systemic toxic effects of the test item were found.
Other findings:
none

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 value of the test item was greater than 2000 mg/kg bw in male and female Crl(WI)Br rats.
Executive summary:

An acute dermal toxicity study was performed with the test item cesium iodide in Crl(WI)Br rats, in compliance with OECD Guideline No. 402 and EU Method B.3. A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to the test item at 2000 mg/kg bw by dermal route. The test item was applied in its original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

No mortality occurred after the single dermal administration of cesium iodide at a dose of level 2000 mg/kg bw with an exposure period of 24 h. No test item related systemic toxic clinical signs were observed and no test item related effects on the animal’s body weights were established throughout the study. The general symptoms observed could not be connected to a toxic effect of the test item but may be related to the induced stress during the treatment procedure (for example due to the presence of the bandage etc.). Autopsy revealed no treatment related pathological changes.

In this acute dermal toxicity study with the test item cesium iodide, the obtained acute dermal LD50 valuewas greater than 2000 mg/kg bw in male and female Crl(WI)Br rats.