Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study described in the publication meets generally accepted scientific principles, acceptable for assessment.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Contact Sensitivity to Arsenical Compounds
Author:
Wahlberg, J.E. & Boman, A.
Year:
1986
Bibliographic source:
Dermatosen 34 (1): 10-12

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
, adopted 12-05-1981
GLP compliance:
not specified
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material: Disodium hydrogen arsenate (pa. Merck AG, Darmstadt, FR Germany)
- Molecular formula (if other than submission substance): Na2HAsO4 * 7 H2O
- Name of test material: Sodium-meta-arsenite (pa. Merck AG, Darmstadt, FR Germany)
- Molecular formula (if other than submission substance): NaAsO2

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
not specified
Details on test animals and environmental conditions:
no data

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: distilled water (induction) and saline (challenge)
Concentration / amount:
Induction:
Na2HAsO4
- intradermal injection: 4% (w/w)
- topical application: 20% (w/w)
NaAsO2
- intradermal injection: 0.2% (w/w)
- topical application: 0.5% (w/w)
Challenge:
Na2HAsO4: 1.0, 0.5 and 0.1% solutions in saline
NaAsO2: 0.1, 0.05 and 0.01% solutions in saline
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: distilled water (induction) and saline (challenge)
Concentration / amount:
Induction:
Na2HAsO4
- intradermal injection: 4% (w/w)
- topical application: 20% (w/w)
NaAsO2
- intradermal injection: 0.2% (w/w)
- topical application: 0.5% (w/w)
Challenge:
Na2HAsO4: 1.0, 0.5 and 0.1% solutions in saline
NaAsO2: 0.1, 0.05 and 0.01% solutions in saline
No. of animals per dose:
20 animals
Details on study design:
Guinea pigs were exposed in groups of 20 animals to Na2HAsO4 and NaAsO2 according to the GPMT method under conditions previously reported (J.E. Wahlberg & A. Boman (1978)*; J.E. Wahlberg & A. Boman (1985)**).

MAIN STUDY
A. INDUCTION EXPOSURE
At induction 4% Na2HAsO4 (w/w) was used for intradermal injection and 20% (w/w) - after treatment for 24 h with 10% sodium lauryl sulphate in petrolatum - for topical application. For NaAsO2 0.2% (w/w) was used for intradermal injection and 0.5% (w/w) for topical application. Distilled water was used as vehicle.

B. CHALLENGE EXPOSURE
Challenge testing was performed on day 21 using 1.0, 0.5 and 0.1% solutions of Na2HAsO4 in saline and 0.1, 0.05 and 0.01% solutions of NaAsO2 in saline. Testing for cross reactivity was performed simultaneously.

ATOMIC ABSORPTION SPECTROPHOTOMETRY: the arsenic compounds used for the guinea pig maximisation test (GPMT) were analysed with a Perkin Elmer 303 atomic absorption spectrophotometer in order to identify impurities of other metals (i.e. nickel or cobalt) contributing to the test reactions.

References:
* Wahlberg, J.E., Boman, A. (1978) Sensitization and testing of guinea pigs with cobalt chloride, Contact Dermatitis 4, 128 - 132.
** Wahlberg, J.E., Boman, A. (1985) Guinea pig maximization test in Curr. Probl. Derm. 14, Anderson, K.E., Maibach, H.I. (Eds.), S. Karger, Basel (1985) (in press).
Challenge controls:
Sham-treated control groups (20 animals per group) were run in each experiment.
Positive control substance(s):
not specified

Study design: in vivo (LLNA)

Statistics:
Chi-square test

Results and discussion

Positive control results:
no data

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1.0% (w/w) of Na2HAsO4 * 7 H2O
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1.0% (w/w) of Na2HAsO4 * 7 H2O. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5% (w/w) of Na2HAsO4 * 7 H2O
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5% (w/w) of Na2HAsO4 * 7 H2O. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.1% (w/w) of Na2HAsO4 * 7 H2O
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1% (w/w) of Na2HAsO4 * 7 H2O. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1.0% (w/w) of Na2HAsO4 * 7 H2O
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1.0% (w/w) of Na2HAsO4 * 7 H2O. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5% (w/w) of Na2HAsO4 * 7 H2O
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.5% (w/w) of Na2HAsO4 * 7 H2O. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.1% (w/w) of Na2HAsO4 * 7 H2O
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.1% (w/w) of Na2HAsO4 * 7 H2O. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.1% (w/w) of NaAsO2
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1% (w/w) of NaAsO2. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.05% (w/w) of NaAsO2
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.05% (w/w) of NaAsO2. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.01% (w/w) of NaAsO2
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.01% (w/w) of NaAsO2. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.1% (w/w) of NaAsO2
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.1% (w/w) of NaAsO2. No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.05% (w/w) of NaAsO2
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.05% (w/w) of NaAsO2. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.01% (w/w) of NaAsO2
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.01% (w/w) of NaAsO2. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

Atomic absorption spectrophotometry

NaAsO2 contained 0.3 ppm cobalt and less than 0.2 ppm nickel and NaHAsO4 less than 0.2 ppm nickel and cobalt.

GMPT Test results:

No statistically significant difference between the exposed and the control groups was seen. There was no evidence of cross-reactivity.

Reading

Hours after challenge

Group

Dose level

No. with + reactions

Total no. in group

Cliinical observations

1streading

24

test group

1.0% (w/w) of  

Na2HAsO4 * 7 H2O

2

19

2ndreading

 48

test group

1.0% (w/w)  

of 

Na2HAsO4 * 7 H2O

0

19

1streading

24

test group

0.5% (w/w)  

of 

Na2HAsO4 * 7 H2O

0

19

2ndreading

 48

test group

0.5% (w/w)  

of 

Na2HAsO4 * 7 H2O

0

19

1streading

24

test group

0.1% (w/w)  

of 

Na2HAsO4 * 7 H2O

0

19

2ndreading

 48

test group

0.1% (w/w)  

of 

Na2HAsO4 * 7 H2O

0

19

1streading

24

negative control

1.0% (w/w)  

of 

Na2HAsO4 * 7 H2O

1

20

2ndreading

 48

negative control

1.0% (w/w)  

of 

Na2HAsO4 * 7 H2O

0

20

1streading

24

negative control

0.5% (w/w)  

of 

Na2HAsO4 * 7 H2O

0

20

2ndreading

 48

negative control

0.5% (w/w)  

of 

Na2HAsO4 * 7 H2O

0

20

1streading

24

negative control

0.1% (w/w)  

of 

Na2HAsO4 * 7 H2O

0

20

2ndreading

48 

negative control

0.1% (w/w)  

of 

Na2HAsO4 * 7 H2O

0

20

1streading

24

test group

0.1% (w/w) of  

NaAsO2

4

20

2ndreading

48 

test group

0.1% (w/w)  

of 

NaAsO2

0

20

1streading

24

test group

0.05% (w/w)  

of 

NaAsO2

0

20

2ndreading

 48

test group

0.05% (w/w)  

of 

NaAsO2

0

20

1streading

24

test group

0.01% (w/w)  

of 

NaAsO2

0

20

2ndreading

48 

test group

0.01% (w/w)  

of 

NaAsO2

0

20

1streading

24

negative control

0.1% (w/w)  

of 

NaAsO2

4

20

2ndreading

 48

negative control

0.1% (w/w)  

of 

NaAsO2

1

20

1streading

24

negative control

0.05% (w/w)  

of 

NaAsO2

0

20

2ndreading

 48

negative control

0.05% (w/w)  

of 

NaAsO2

0

20

1streading

24

negative control

0.01% (w/w)  

of 

NaAsO2

0

20

2ndreading

 48

negative control

0.01% (w/w)  

of 

NaAsO2

0

20

Control groups treated with saline showed no reaction.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The sensitive predictive test method (GMPT) did not disclose the studied arsenicals to be allergens.
According to 67/548/EC and subsequent regulations, the substance is not classified as a skin sensitiser.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the substance is not classified as a skin sensitiser.