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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:
August 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Principles of method if other than guideline:
Method: variation of Magnusson and Kligman method
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method.

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium Salts of (1-Hydroxyethylidene)bisphosphonic acid (2-3 Na:1)
EC Number:
701-238-4
Cas Number:
29329-71-3
Molecular formula:
HEDP-2Na C2H6Na2O7P2 HEDP-3Na C2H5Na3O7P2
IUPAC Name:
Sodium Salts of (1-Hydroxyethylidene)bisphosphonic acid (2-3 Na:1)
Test material form:
not specified

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not specified
- Females nulliparous and non-pregnant: Not specified
- Microbiological status of animals, when known: Not specified
- Age at study initiation: Not specified
- Weight at study initiation: Median body weight for the test group: 403 grams; Median body weight for the control group: 402 grams. No further details available.
- Housing: Not specified
- Diet: Not specified
- Water: Not specified
- Acclimation period: Not specified
- Indication of any skin lesions: Not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not specified
- Humidity (%): Not specified
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): Not specified
- IN-LIFE DATES: Not specified

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
other: water, Freund's Adjuvant (intradermal induction) and Vaseline (topical induction and challenge)
Concentration / amount:
5% induction, 25% challenge
Challenge
Route:
epicutaneous, semiocclusive
Vehicle:
other: water, Freund's Adjuvant (intradermal induction) and Vaseline (topical induction and challenge)
Concentration / amount:
5% induction, 25% challenge
No. of animals per dose:
20 animals for the test group and 20 animals for the control group.
Details on study design:
RANGE FINDING TESTS: Not specified

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Initially, 6 injections were performed (symmetrically and simultaneously). A week later, a topical induction was performed.
- Exposure period: A week
- Test groups: Not specified
- Control group: Not specified
- Site: Around the shoulder blades
- Frequency of applications: Initially, 6 injections were performed simultaneously followed by a topical induction a week later consisting of a 5% mixture in Vaseline, under a 2 x 4 cm piece of filter paper.
- Duration: The occlusive covering covered the site of topical induction for 48 hours
- Type of covering: Occlusive covering of watertight plastic and an elastic bandage.
- Concentrations:
2 x 0.1 ml Freund's Adjuvant (foremost two sites)
2 x 0.1 ml 5% aqueous solution of test substance (middle two sites)
2 x 0.1 ml Mixture (1:1) of 5% aqueous solution of test substance and Freund's Adjuvant (hindmost two sites).
As the concentration of the test substance is not clear, there is no evidence that this induction dose was irritating.

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: 14 days
- Exposure period: Appearing to be 21 hours (not clearly stated). 21 hours after the challenge, the area was re-shaved and remaining test substance was carefully removed with ether.
- Test groups: Not specified
- Control group: Not specified
- Site: 5 x 5 cm area around the flanks
- Type of covering: A 2 x 2 cm piece of filter paper, no occlusive covering appears to have been applied at this stage.
- Concentrations: 25 % mixture in Vaseline
- Evaluation (hr after challenge): 3 hours

OTHER: Areas were shaved or re-shaved prior to the application of the test substance.

1st application: Induction 5 % intracutaneous
2nd application: Induction 5 % occlusive epicutaneous
3rd application: Challenge 25 % semiocclusive
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
No. with + reactions:
8
Total no. in group:
20
Clinical observations:
erythema, grade 1 - slight redness
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
erythema, grade 1 - slight redness, reversible within 72 hours
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
6
Total no. in group:
20
Clinical observations:
erythema, grade 1 - slight redness
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
erythema, grade 1 - slight redness, reversible within 72 hours
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
positive control
Remarks on result:
not measured/tested
Reading:
2nd reading
Group:
positive control
Remarks on result:
not measured/tested

Any other information on results incl. tables

TEST SUBSTANCE GROUP RESPONSES
24 hours: 8 animals (erythema: grade 1 - slight redness)
48 hours: 5 animals (erythema: grade 1 - slight redness)
72 hours: 0 animals displaying symptoms

CONTROL GROUP RESPONSES
24 hours: 6 animals (erythema: grade 1 - slight redness)
48 hours: 2 animals (erythema: grade 1 - slight redness)
72 hours: 0 animals displaying symptoms

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In a guinea-pig maximisation study (reliability score 2), not conducted according to any OECD Test Guideline and pre-GLP, HEDP (2-3Na) is not sensitising to the skin of guinea pigs.