Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6 November 1992 to 7 January 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Diammonium bis[carbonato-O]dihydroxyzirconate
EC Number:
269-682-7
EC Name:
Diammonium bis[carbonato-O]dihydroxyzirconate
Cas Number:
68309-95-5
Molecular formula:
C2H2O8Zr.2H4N
IUPAC Name:
diammonium bis[carbonato-O]dihydroxyzirconate
Details on test material:
Batch number 92/170 BT. Purity not specified but assumed to be consistent with that specified in section 1.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
Fifty two young adult (less than one year old), nulliparous and non-pregnant, female albino guinea pigs of the Dunkin-Hartley strain, within the weight range 349-455 g at main test commencement, were used. They were supplied by David Hall Limited, Darley Oaks, Newchurch, Burton-on-Trent, Staffordshire, and arrived at Elphinstone Research Centre on 1 December 1992. The sensitivity of this strain of guinea pig to a known sensitiser, 2,4-dinitro-chlorobenzene (DNCB), is checked at 6 monthly intervals. The most recent positive control test with DNCB was completed on 14 September 1992 when 60% of the test group animals reacted positively.

Twenty test group and 20 control group guinea pigs were housed 5 to a cage. Twelve dose ranging guinea pigs were housed 4 to a cage in 3 further cages. Each aluminium cage had a grid floor beneath which was an absorbent paper lined tray.

The animals were fed FD1 Guinea Pig Diet, supplied by Special Diets Services Limited, 1 Stepfield, Witham, Essex, CM8 3AD, supplemented with hay and allowed food and tap water ad libitum. The diet and water are analysed on a regular basis and meet the criteria laid down by IRI.

Mean environmental maximum and minimum temperatures were 20°C and 19°C and mean relative humidity was 50%. A 12 h light/dark cycle was in operation (light hours 0700-1900 h).

The dose ranging guinea pigs were allowed an acclimatisation period of 7 days prior to test commencement and the main study animals were allowed an acclimatisation period of 13 days.

The guinea pigs were identified by means of indelible ear marks and colour code using a system routinely used at IRI. Main study animals were weighed at test commencement and completion.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
RF study
Injections: 100%, 75%, 50%, 25%, 10%, 5% 2% and 1% v/v in distilled water
Topical application: 100%, 75%, 50%, 25%, 10%, 5% 2% and 1% v/v in distilled water

MAIN study
Induction phase: Injection: 10% in distilled water; Topical: 100% (pre-treated with 10% aqueous SLS)
Challenge: 100%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
RF study
Injections: 100%, 75%, 50%, 25%, 10%, 5% 2% and 1% v/v in distilled water
Topical application: 100%, 75%, 50%, 25%, 10%, 5% 2% and 1% v/v in distilled water

MAIN study
Induction phase: Injection: 10% in distilled water; Topical: 100% (pre-treated with 10% aqueous SLS)
Challenge: 100%
No. of animals per dose:
In the dose ranging test for induction four guinea pigs were exposed to intradermal injections and four to topical applications at the concentrations
given above.
Challenge controls:
20 control group animals were used in the challenge phase.
Positive control substance(s):
yes
Remarks:
2,4-dinitro-chlorobenzene (DNCB)

Results and discussion

Positive control results:
Last study completed on 14 September 1992. 60% of the test group animals reacted positively.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100% v/v
No. with + reactions:
0
Total no. in group:
17
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100% v/v. No with. + reactions: 0.0. Total no. in groups: 17.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100& v/v
No. with + reactions:
0
Total no. in group:
17
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100& v/v. No with. + reactions: 0.0. Total no. in groups: 17.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% v/v
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100% v/v. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
100% v/v
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100% v/v. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.

Any other information on results incl. tables

Dose Ranging Test for Induction

 

Moderate irritation was noted at sites injected with Ammonium Zirconium Carbonate at concentrations of 100%, 75%, 50% and 25% v/v in distilled water. A concentration of 10% v/v in distilled water was selected for the injection phase of induction in the test group, this being the highest concentration that produced only slight irritant responses.

 

No irritation was noted at sites treated topically with the test material. A concentration of 100% was selected for the topical application phase of induction in the test group.

 

Main Test - Induction

 

Slight to severe irritation was noted in the test group and slight to moderate irritation noted in the control group.

 

Dose Ranging Test for Challenge

 

No irritation was noted at sites treated topically with Ammonium Zirconium Carbonate at concentrations of 100%, 75%, 50% and 25% v/v in distilled water. A concentration of 100% was selected for challenge.

Main Test - Challenge

 

Three of the test group animals were sacrificed prior to challenge due to lesions at the scapular test sites which exceeded the severity limit for the test.

 

Following challenge with Ammonium Zirconium Carbonate at a concentration of 100%, none of the 17 test group animals showed positive reactions to this application. None of the 20 control group animals, which had previously only been exposed to the vehicle, distilled water, showed a positive reaction to this application.

 

There was no reaction in the test or control groups to challenge with the vehicle, distilled water.

 

Body Weight

 

Body weights were recorded at main test commencement and on test completion. Body weight gains were acceptable.

 

Clinical_Signs

 

No clinical signs, other than skin reactions induced by treatment,were noted.


Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Following challenge with Ammonium Zirconium Carbonate at a concentration of 100%, none of the 17 test group animals showed positive reactions to this application. None of the 20 control group animals, which had previously only been exposed to the vehicle, distilled water, showed a positive reaction to this application. The substance is considered to be a non-sensitiser under the conditions of the test.
Executive summary:

A GLP-compliant Magnusson & Kligman maximisation study according to OECD Guideline 406 has been conducted.Concentrations used for the induction phase were 10% in distilled water for the injections, and 100% for the topical application (preceded by wetting with 10% SLS to create local irritation). Following challenge with Ammonium Zirconium Carbonate at a concentration of 100%, none of the 17 test group animals showed positive reactions to this application. None of the 20 control group animals, which had previously only been exposed to the vehicle, distilled water, showed a positive reaction to this application. The substance is considered to be a non-sensitiser under the conditions of the test.