Diarsenic trioxide

Skin sensitisation

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:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Contact sensitivity to arsenical compounds

Author:

Wahlberg, J.E. and Boman, A.

Year:

1986

Bibliographic source:

Dermatosen 34 (1):10-12

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

, adopted 12-05-1981

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

This study, published in 1986, has been conducted at a time when the guinea pig maximisation test (GPMT) was also an accepted method. It provides adequate information for the assessment of the skin sensitisation potential of the test item(s).

Test material

Test material information

Constituent 1

Reference substance name:

sodium dioxoarsenate and disodium hydrogenarsenate

IUPAC Name:

sodium dioxoarsenate and disodium hydrogenarsenate

Constituent 2

Reference substance name:

232-070-5 and 231-902-4

IUPAC Name:

232-070-5 and 231-902-4

Constituent 3

Reference substance name:

7784-46-5 and 7778-43-0

IUPAC Name:

7784-46-5 and 7778-43-0

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)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: distilled water (induction) and saline (challenge)

Induction 2

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

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: distilled water (induction) and saline (challenge)

Challenge 2

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

Results and discussion

Positive control results:

no data

In vivo (non-LLNA)

Results

Results 1

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

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.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

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.

Results 3

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

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.

Results 4

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.

Results 5

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.

Results 6

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.

Results 7

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

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.

Results 8

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

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.

Results 9

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

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.

Results 10

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.

Results 11

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.

Results 12

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.

Results 13

Reading:

other: no positive control used in study

Hours after challenge:

0

Group:

positive control

Dose level:

0

No. with + reactions:

0

Total no. in group:

0

Remarks on result:

other: no positive control used in study

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
1^streading	24	test group	1.0% (w/w) of   Na2HAsO4 * 7 H2O	2	19
2^ndreading	48	test group	1.0% (w/w)   of  Na2HAsO4 * 7 H2O	0	19
1^streading	24	test group	0.5% (w/w)   of  Na2HAsO4 * 7 H2O	0	19
2^ndreading	48	test group	0.5% (w/w)   of  Na2HAsO4 * 7 H2O	0	19
1^streading	24	test group	0.1% (w/w)   of  Na2HAsO4 * 7 H2O	0	19
2^ndreading	48	test group	0.1% (w/w)   of  Na2HAsO4 * 7 H2O	0	19
1^streading	24	negative control	1.0% (w/w)   of  Na2HAsO4 * 7 H2O	1	20
2^ndreading	48	negative control	1.0% (w/w)   of  Na2HAsO4 * 7 H2O	0	20
1^streading	24	negative control	0.5% (w/w)   of  Na2HAsO4 * 7 H2O	0	20
2^ndreading	48	negative control	0.5% (w/w)   of  Na2HAsO4 * 7 H2O	0	20
1^streading	24	negative control	0.1% (w/w)   of  Na2HAsO4 * 7 H2O	0	20
2^ndreading	48	negative control	0.1% (w/w)   of  Na2HAsO4 * 7 H2O	0	20
1^streading	24	test group	0.1% (w/w) of   NaAsO2	4	20
2^ndreading	48	test group	0.1% (w/w)   of  NaAsO2	0	20
1^streading	24	test group	0.05% (w/w)   of  NaAsO2	0	20
2^ndreading	48	test group	0.05% (w/w)   of  NaAsO2	0	20
1^streading	24	test group	0.01% (w/w)   of  NaAsO2	0	20
2^ndreading	48	test group	0.01% (w/w)   of  NaAsO2	0	20
1^streading	24	negative control	0.1% (w/w)   of  NaAsO2	4	20
2^ndreading	48	negative control	0.1% (w/w)   of  NaAsO2	1	20
1^streading	24	negative control	0.05% (w/w)   of  NaAsO2	0	20
2^ndreading	48	negative control	0.05% (w/w)   of  NaAsO2	0	20
1^streading	24	negative control	0.01% (w/w)   of  NaAsO2	0	20
2^ndreading	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:

GHS criteria not met

Conclusions:

The sensitive predictive test method (GMPT) does not suggest that the studied arsenicals are skin allergens.
According to Regulation (EC) No. 1272/2008 and subsequent regulations, the substance is not classified as a skin sensitiser.