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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
06/03/1990 to 18/04/1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study. Read-across is justified on the following basis: The family of zinc borates that include Zinc Borate 500, Zinc Borate 2335 and Zinc Borate 415 (also known as Zinc Borate 411). Zinc borate 500 is anhydrous Zinc Borate 2335 and Zinc Borate 415 has different zinc to boron ratio. Zinc borate 2335 (in common with other zinc borates such as Zinc borate 415 and 500) breaks down to Zinc Hydroxide (via Zinc oxide) and Boric Acid, therefore the family of zinc borates shares the same toxicological properties. Zinc borates are sparingly soluble salts. Hydrolysis under high dilution conditions leads to zinc hydroxide via zinc oxide and boric acid formation. Zinc hydroxide and zinc oxide solubility is low under neutral and basic conditions. This leads to a situation where zinc borate hydrolyses to zinc hydroxide, zinc oxide and boric acid at neutral pH quicker than it solubilises. Therefore, it can be assumed that at physiological conditions and neutral and lower pH zinc borate will be hydrolysed to boric acid, zinc oxide and zinc hydroxide. Hydrolysis and the rate of hydrolysis depend on the initial loading and time. At a loading of 5% (5g/100ml) zinc borate hydrolysis equilibrium may take 1-2 months, while at 1 g/l hydrolysis is complete after 5 days. At 50 mg/l hydrolysis and solubility is complete (Schubert et al., 2003). At pH 4 hydrolysis is complete. Zinc Borate 2335 breaks down as follows: 2ZnO • 3B2O3 •3.5H2O + 3.5H2O + 4H+ ↔ 6H3BO3 + 2Zn2+ 2Zn2+ + 4OH- ↔ 2Zn(OH)2 ____________________________________________________________ Overall equation 2ZnO • 3B2O3 •3.5H2O + 7.5H2O ↔ 2Zn(OH)2 + 6H3BO3 The relative zinc oxide and boric oxide % are as follows: Zinc borate 2335:zinc oxide = 37.45% (30.09% Zn) B2O3 = 48.05% (14.94% B) Water 14.5% Zinc borate 415: zinc oxide = 78.79%; (63.31% Zn) B2O3 = 16.85% (5.23% B) Water 4.36% Zinc borate, anhydrous: Zinc oxide = 45 % B2O3= 55% (17.1 % B)
Qualifier:
according to guideline
Guideline:
other: Federal Insecticide, Fungicide and Rodenticide Act (40 CFR)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
other: Toxic Substances Control Act (40 CFR)
Deviations:
not specified
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
OECD Guideline 406 "Skin Sensitisation" method (Buehler test ) was performed before the LLNA was set as preferred test method.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Murphy Breeding Laboratories, Inc.
- Weight at study initiation: 381 - 538 g
- Housing: Individually in wire mesh suspension cages.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: Animals will be quarantined for at least 4 days.

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light cycle.

IN-LIFE DATES: From: 12/03/1990 To: 18/04/1990
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
75 % w/v formulation in distilled water.
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
75 % w/v formulation in distilled water.
No. of animals per dose:
Pilot studies: Four in each of two pilots
Main study: See table.
Details on study design:
RANGE FINDING TESTS:
Pilot No. 1: Six h patch test at 5 %, 2.5 %, 1 % and 0.5 % w/v using 2 males and 2 females.
Pilot No. 2: Six h patch test at 75 %, 50 %, 25 % and 10 % w/v using 2 males and 2 females.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three
- Exposure period: 6-hours per exposure
- Site: Left shoulder
- Frequency of applications: Once per week

B. CHALLENGE EXPOSURE
- No. of exposures: Single challenge
- Day(s) of challenge: Approximately two weeks after last induction.
- Site: Varied, but on skin that had not previously been previously exposed.
- Concentrations: 75 % w/v
- Evaluation (hr after challenge): 24 and 48 h
Positive control substance(s):
yes
Remarks:
Historical data on DNCB
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75 % w/v
No. with + reactions:
9
Total no. in group:
20
Clinical observations:
Slightly patchy erythema.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75 % w/v. No with. + reactions: 9.0. Total no. in groups: 20.0. Clinical observations: Slightly patchy erythema..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75 % w/v
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 75 % w/v. No with. + reactions: 7.0. Total no. in groups: 10.0.

The incidence and severity of responses were calculated as follows:

Group

Test materiala

Concentrationb

Incidence of responses

Mean severity scores

24 h

48 h

0

±

1

2

3

0

±

1

2

3

24 h

48 h

Primary challenge

Test

TMID

75 %

13

7

0

0

0

15

5

0

0

0

0.2

0.1

Naïve control

TMID

75 %

4

6

0

0

0

3

7

0

0

0

0.3

0.4

aTMID- FIREBRAKE®ZB zinc borate 2335

bTest material formulated w/v in distilled water

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The potential for FIREBRAKE® ZB zinc borate 2335 as a 75 % w/v formulation in distilled water to produced delayed contact hypersensitivity in guinea pigs was evaluated using an adaptation of the method of Buehler. Following primary challenge there were no grades of 1 produced in the test or control animals. The incidence of grade ± responses in the test group (9 of 20) was compared to that of the naive control group (7 of 10). The incidence of these responses in the test group was less than that produced by the naive control group indicating that sensitisation had not been induced.
Read-across is justified on the basis detailed in the rationale for reliability above. This study is therefore considered to be of sufficient adequacy and reliability to be used as a key study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Zinc borate was tested in a Buehler method skin sensitisation test (Kreuzmann, 1990) applied at a concentration of 75 % (powder moistened with water) during both the induction and challenge phase of the test. No signs of skin sensitisation were observed.

See toxicokinetic section for read-across justification.


Migrated from Short description of key information:
A skin sensitisation test on zinc borate was performed according to OECD Guideline 406 (Buehler method).

Justification for selection of skin sensitisation endpoint:
Key study conducted with zinc borate heptahydrate.

Respiratory sensitisation

Endpoint conclusion
Additional information:
Migrated from Short description of key information:
There are no data to suggest that zinc borate is respiratory sensitiser.

Justification for classification or non-classification

Zinc borate is not a skin or respiratory sensitiser.

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