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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:
16 February to 04 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 guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solution
Details on test material:
The test material was dichromium tris(chromate) 25% solution, batch no. RCAJ29F1TOX, described as a dark brown liquid. The batch had an expiry date of November 2010, and was stored at room temperature.
All concentrations were expressed as active ingredient.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
The animals were young adult male/female CRL:(WI) BR SPF rats, obtained from TOXI-COOP Ltd (Budapest). At the start of the study the females were 7-8 weeks old and the males were 6-7 weeks, the weight range at dosing was 200-251 g. Females were nulliparous and non-pregnant. The rats were acclimatised for 6-8 days. Only healthy animals (veterinary surgeon certified) were used for the study.
Rats were individually housed in Type II polypropylene/polycarbonate cages with Lignocel Bedding (a copy of the certificate of analysis was retained by the test facility). The temperature in the animal room was 22±3°C, relative humidty was 30-70%, there were 15-20 air changes per hour and light was provided for 12 hours daily.
Animals were fed ssniff SM R/M-Z+H "Autoclavable complete feed for rats and mice - breeding and maintenance" (ssniff Spezialdiaten GmbH, Germany) ad libitum. Tap water from the municipal supply was provided ad libitum.
Individuals were identified by indelible ink markings on the tail.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Doses of 175, 350 and 850 mg active ingredient/kg bw (equivalent to 741, 1483 and 3602 mg/kg of 25% solution) were tested initially. Two days later additional doses of 1400 and 2000 mg active ingredient/kg bw (equivalent to 5932 and 8475 mg/kg of 25% solution) were chosen after discussion with the sponsor. A preliminary study was performed to identify appropriate dose ranges.
The test material was applied as supplied.

An area of approximately 10% of the total body surface on the back of each animal was shaved approximately 24 hours prior to treatment. The test item was applied as a single dose, and was held in contact with the skin for 24 hours using sterile gauze pads covered with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with a semi-occlusive plastic wrap. After 24 hours the wrappings were removed and the test site was washed with water at body temperature.
Duration of exposure:
24 hours
Doses:
175, 350, 850, 1400 and 2000 mg active ingredient/kg bw.
No. of animals per sex per dose:
1 rat/sex/dose
Control animals:
not required
Details on study design:
Clinical observations were made at 1 and 5 hours after application of the test material, and once daily thereafter for 14 days. Observations were made of the skin, fur, eyes, mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was given to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Body weights were recorded immediately before test item administration (day 0), and on days 7 and 14.
Gross necropsy was performed on all animals. Animals were euthanised by exsanguination under pentobarbital anaesthesia. The rats were examined externally, then the cranial, thoracic and abdominal cavities were opened and the tissues and organs examined macroscopically.
Statistics:
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:
act. ingr.
Mortality:
No mortalities occurred.
Clinical signs:
No clinical signs were observed.
Body weight:
There were no effects of treatment on body weight or body weight gain.
Gross pathology:
The only macroscopic findings were dark/brown discolouration of the fur at the dosing site in 1/2, 2/2 and 2/2 animals at dose levels of 850, 1400 and 2000 mg/kg, respectively.
Other findings:
Brownish staining of the hair and skin was observed from Day 1 up to Day 8 in 6 animals. Brownish staining of the hair was observed from Day 9 to 14 in five animals. No local signs of skin aleration were observed during the observation period.

Any other information on results incl. tables

No further information.

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 of Dichromium tris(chromate), tested as a water solution (23.6% active ingredient) was found to be >2000 mg active ingredient/kg bw in male and female rats.
Executive summary:

The acute dermal toxicity of Dichromium tris(chromate) water solution (23.6% active ingredient) was evaluated in male and female CRL:(WI) BR rats, according to OECD 402. The test material was applied to the shaved dorsal skin of 1 male and 1 female rat per dose, and held in place using a semi-occlusive dressing for 24 hours. Dose levels applied, expressed in terms of active ingredient, were; 175, 350, 850, 1400 and 2000 mg/kg bw. The rats were observed for 14 days following removal of the dressings, and were necropsied at the end of the observation period.

There were no mortalities, no clinical signs were observed, no abnormalities were detected at necropsy, and no local effects on skin reported. Brownish staining of the hair and skin was observed from Day 1 up to Day 8 in 6 animals, and brownish staining of the hair was observed from Day 9 to 14 in 5 animals. Discolouration of the hair at the test site was also noted at necropsy in rats at dose levels 850, 1400 and 2000 mg active ingredient/kg.

It was concluded that the acute dermal LD50 of Dichromium tris(chromate) is greater than 2000 mg/kg bw in male and female CRL:(WI) rats.