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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
3 September 2009 to 17 September 2009
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A GLP study performed to standardised guidelines with a sufficient level of detail to assess the quality of the submitted data.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

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

Constituent 1
Reference substance name:
Ammonium Zirconium Carbonate
IUPAC Name:
Ammonium Zirconium Carbonate
Test material form:
not specified

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Five male and five female Wistar (HsdRccHan®TM:WIST®TM) strain rats were supplied by Harlan Laboratories UK Limited, Bicester, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals weighed at least 200g, and were eight to twelve weeks of age. The weight variation did not exceed ± 20% of the mean weight for each sex.

The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The calculated volume of test material, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The animals were caged individually for the 24-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Duration of exposure:
24 hours
Doses:
Animals received a single dose of 2000 mg/kg bw of the test material (892 mg/kg of AZC and 390 mg/kg of ZrO2)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not required
Details on study design:
On the day before treatment the back and flanks of each animal were clipped free of hair.

Using available information on the toxicity of the test material, a single group of animals (5 males and 5 females) was treated with a dose level of 2000 mg/kg of the test substance.

The calculated volume of test material, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The animals were caged individually for the 24-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.

After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31:
Statistics:
Not applicable

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All male animals and one female animal showed expected gains in bodyweight over the study period. Bodyweight loss or no gain in bodyweight was noted in four females during the first week with expected gain in bodyweight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Very slight erythema was noted at the test sites of two males and three females two days after dosing. This was observed on a single day in one male and two females, and persisted in one male and one female three and four days after dosing. No other signs of dermal irritation were noted.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of Ammonium Zirconium Carbonate (44.6% aqueous solution of AZC equivalent) in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight, with no deaths and no signs of systemic toxicity at this dose level.
Executive summary:

In order to assess the acute dermal toxicity of the test substance registered a study with the analogue substanceammonium zirconium carbonate (44.6% aqueous solution of AZC equivalent) wasevaluated.Please refer to point 5.2.1 above and to the document "KZC consolidated read-across report", as attached to Section 13 of the IUCLID, for a detailed justification for this proposed read-across.Theacute dermal median lethal dose (LD₅₀) of ammonium zirconiumcarbonate in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight in an OECD 402 study, with no deaths and no signs of systemic toxicity at this dose level.