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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
no information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Deviations from the current test method; some information is lacking. However, useful in ‘weight of evidence’ approach
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
other: short communication
Title:
Unnamed
Year:
1979

Materials and methods

Principles of method if other than guideline:
The skin sensitisation potential of the test material was evaluated in two series of guineapig maximisation tests using the test material at a concentrations upto 0.5%.
GLP compliance:
not specified
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Cadmium chloride
EC Number:
233-296-7
EC Name:
Cadmium chloride
Cas Number:
10108-64-2
Molecular formula:
CdCl2
IUPAC Name:
cadmium(2+) dichloride
Details on test material:
water soluble cadmium compound CdCl2; analytical purity

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
none

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
petrolatum
Concentration / amount:
up to 0.5% CdCl2
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
petrolatum
Concentration / amount:
up to 0.5% CdCl2
No. of animals per dose:
20
Details on study design:
In a first series 20 guinea pigs were utilised in the treated group (CdCl2, analytical purity) and 20 animals treated in the same way with exception of the test substance were foreseen as control group. For intradermal induction, a 0.007% CdCl2 in water and Freund's complete adjuvants was used. For topical application a 5.0% CdCl2 in petrolatum (w/w) was applied.
Solvent : intradermal induction = water; topical application = petrolatum

Three weeks after induction, epicutaneous challenge were given with 0.5% substance in petrolatum, 0.1% and the control sensitised group. Readings were done 24h and 48h after removal of the aluminum test chambers (so called Finn chambers) on the previously shaved flanks.

In the second series, 19 animals were treated and 18 controls were used and the CdCl2 concentration for induction had been raised to 0.05% for intradermal injection and 7.5% CdCl2 for topical application. Challenging concentrations were 0.5%, 0.25% and 0.05% and petrolatum (control). Readings were conducted blind after 24 h and 48 h.
Challenge controls:
control: petrolatum
Positive control substance(s):
no

Study design: in vivo (LLNA)

Vehicle:
other: not applicable
Concentration:
not applicable
No. of animals per dose:
not applicable
Details on study design:
not applicable
Positive control substance(s):
other: not applicable
Statistics:
chi-square test

Results and discussion

Positive control results:
not applicable

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
other: challenged group
Dose level:
0.1%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
unspecified skin reactions
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: challenged group. Dose level: 0.1%. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: unspecified skin reactions.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: challenged group
Dose level:
0.1%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
unspecified skin reactions
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: challenged group. Dose level: 0.1%. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: unspecified skin reactions.
Reading:
1st reading
Hours after challenge:
24
Group:
other: challenged group
Dose level:
0.5%
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
unspecified skin reaction
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: challenged group. Dose level: 0.5%. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: unspecified skin reaction.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: challenged group
Dose level:
0.5%
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
unspecified skin reactions
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: challenged group. Dose level: 0.5%. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: unspecified skin reactions.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
unspecified skin reactions
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: unspecified skin reactions.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
unspecified skin reactions
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: unspecified skin reactions.
Reading:
1st reading
Hours after challenge:
24
Group:
other: sensitized + challenged group
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
unspecified skin reactions
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: sensitized + challenged group. Dose level: 0.1%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: unspecified skin reactions.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: sensitized + challenged group
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
unspecified skin reactions
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: sensitized + challenged group. Dose level: 0.1%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: unspecified skin reactions.
Reading:
1st reading
Hours after challenge:
24
Group:
other: sensitized + challenged group
Dose level:
0.5%
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
unspecified skin reactions
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: sensitized + challenged group. Dose level: 0.5%. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: unspecified skin reactions.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: sensitized + challenged
Dose level:
0.5%
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
unspecified skin reactions
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: sensitized + challenged. Dose level: 0.5%. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: unspecified skin reactions.
Reading:
1st reading
Hours after challenge:
24
Group:
other: sensitized group
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
unspecified skin reactions
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: sensitized group. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: unspecified skin reactions.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: sensitized group
Dose level:
0%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
unspecified skin reactions
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: sensitized group. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: unspecified skin reactions.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: not applicable
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: not applicable

Any other information on results incl. tables

The first series of experiments showed the following results in the CdCl2 exposed versus control animals:
24 h readings:

At 0.5% challenge concentration, 2 animals with test reactions in the treated as well as in the control group. At 0.1% challenge concentration, 1 animal reacted in the control group. The control petrolatum challenge gave at 2 positive animals in the control group. 

48 h readings: 

At 0.5% challenge, 4 animals in the control and 4 animals in the exposed group. At 0.1% challenge, 1 animal in the control group. In the control petrolatum challenge, 0 animals in control and treated group.
No further details were given related to the magnitude,severity and type of the skin reactions after challenge(scores are not provided). No second challenge was performed. The results were compared with the chi-square test and the differences were reported as non statistically significant.

The second series of experiments gave the following results:

The differences were observed between the cadmium exposed and the control animals were not statistically significant at any of the challenge
concentrations for any of the readings. In the second series, at challenge concentration of 0.5%, three at 24 h and three at 48 h animals reacted in the treated group compared to one and one in the controls. At challenge
0.25% one at 24 h and one at 48 h control animal reacted and the same was seen in the treated group. At 0.05% one  at 24 h and
one at 48 h control animal reacted compared to zero animals at 24 h and one  animal at 48 h treated animal. The petrolatum challenge gave a
single one reacting animal within the treated group. 

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The test results, although reported by the author as not statistically significant different, do not allow to conclude the absence of sensitising potential of the substance in a standard test system currently used for legal purposes.
Executive summary:

The skin sensitisation potential of the test material was evaluated by the guineapig maximisation test.

Two series of experiments were carried out with the test material concentrations upto 0.5%. Guinea pigs showed no contact sensitization following intradermal or topical exposure to cadmium chloride at concentrations up to 0.5%.

The test is stated to be performed using the Guinea Pig Maximization Test but at least some deviations from the current regulatory test protocol are noticed. Furthermore the study is only briefly reported, no justification for the used dose levels is given, observation at induction are omitted and the challenge results are provided without grading scores