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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-12-03 to 2008-01-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-compliant study under GLP without deviations.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The testing using the guinea pig maximisation test protocol was completed on 17 April 2009. The LLNA 429 was not formally adopted by the OECD until 22 July 2010. Also, according to the OECD, there are limitation to LLNA 429 including false negatives for certain metals.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Beryllium Metal Powder
- Molecular formula (if other than submission substance): Be
- Substance type: Metal
- Physical state: Solid
- Analytical purity: 99.4%
- Lot/batch No.: O-30H grade /Blend # 051106
- Expiration date of the lot/batch: 2050-12-31
- Storage condition of test material: at room temperature protected from light

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS Albino Dunkin Hartley Guinea Pig, CRL:(HA)BR, SPF
- Source: Charles River Lab., Kisslegg, Germany
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 344-372 g
- Housing:individually in macrolon type-4 cages on softwood bedding
- Diet (e.g. ad libitum): pelleted standard guinea pig breeding/maintainance diet, Provimi Kliba, Kaiseraugst, Switzerland, ad lib.
- Water (e.g. ad libitum): community tap water ad lib.
- Acclimation: under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
polyethylene glycol
Concentration / amount:
50 %
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
50 %
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
intradermal injection: highest technically applicable concentration was determined to be 15 % of test item in PEG (higher concentrations were not passing the needle properly).
Epidermal exposure: the highest non-irritating dose was identified to be 10 % test item in PEG and was choosen for challenge. 50 % test item in PEG was used for dermal induction, causing very slight skin reactions.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal, 1 epidermal
- Exposure period: intradermal injection on day 1; epidermal induction on day 8, for 48 h occlusive
- Test groups:

Intradermal:
1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.
2) The test item at 15 % in PEG 300.
3) The test item at 15 % in a 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.

Epidermal:
50 % test item in PEG 300

- Control group:

Intradermal:
1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.
2) PEG 300
3) 1:1 (w/w) mixture of PEG 300 in a 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.

Epidermal:
PEG 300

- Site: scapular area, shaved


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 48 h, epidermal, occlusive
- Test groups: 10 % test item in PEG 300 (left flank), PEG 300 (right flank)
- Control group: 10 % test item in PEG 300 (left flank), PEG 300 (right flank)
- Evaluation (hr after challenge): 24 and 48 h after removal of dressing
Positive control substance(s):
yes
Remarks:
ALPHA-HEXYLCINNAMALDEHYDE

Results and discussion

Positive control results:
All test animals showed skin reactions after the challenge treatment with ALPHAHEXYLCINNAMALDEHYDE
at 3 % in PEG 300.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: 1 st and 2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
10% of test item
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading:
Reading:
other: 1st and 2nd reading
Hours after challenge:
24
Group:
negative control
Dose level:
10% of test item
No. with + reactions:
0
Total no. in group:
5
Reading:
other: 1st and 2nd reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
other: Detailed results were not specified.

Any other information on results incl. tables

Table 1: Animals with positive reactions after challange

     animals with positive reactions/ total animals in group   
     24 h after challange  48 h after challange
 Control Group  test item  0/5  0/5
   vehicle  0/5  0/5
 Test Group  test item  0/10  0/10
   vehicle  0/10  0/10

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Beryllium metal powder was not a skin sensitzer in the guinea pig maximisation test.
Executive summary:

The skin sensitizing potential of beryllium metal powder was investigated in guinea pigs according to OECD guideline 406. For induction of sensitization, male Dunkin-Hartley Guinea Pigs were exposed to the highest technically feasibile concentration of the test item in polyethylene glycol (PEG 300) by intradermal injection together with immunostimulant (Freud's Complete Adjuvant). One week later, the animals were exposed to the test item in PEG 300 by 48 h occlusive epidermal application. Two weeks later, reactions were challanged by epidermal application of test item in PEG 300 (same procedure as for epidermal induction, but different site).

None of the animals showed signs of contact hypersensitivity.