Cyanoguanidine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

number of test animals should be 10 (here: 8)

Principles of method if other than guideline:

The Landsteiner/Draize method was used. The test substance was administered by intra-dermal injections.

GLP compliance:

not specified

Remarks:

pre-GLP

Type of study:

Draize test

Justification for non-LLNA method:

A Skin sensitisation study from 1977 is available

Test material

Test material information

Constituent 1

Reference substance name:

Cyanoguanidine

EC Number:

207-312-8

EC Name:

Cyanoguanidine

Cas Number:

461-58-5

Molecular formula:

C2H4N4

IUPAC Name:

1-cyanoguanidine

Test material form:

solid: particulate/powder

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: not specified; albino guinea pigs

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 198 - 282 g

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

other: 0.85 % saline

Induction 2

Concentration / amount:

2 % solution in 0.85 % saline

Challenge

Challenge 1

Route:

intradermal

Vehicle:

other: 0.85 % saline

Challenge 2

Concentration / amount:

2 % solution in 0.85 % saline

No. of animals per dose:

- 8 animals per group
- 2 groups: 1 test group, 1 control group

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: test group animals were treated repeatedly (10 injections), the control group animals were only treated once
- Duration: 3 weeks
- Test groups: 1
- Control group: 1
- Site: right flank
- Frequency of applications: 3 times weekly
- Concentrations: 2 % colution of the substance in 0.85 % saline
- details on injections: test animals received a total of 10 injections; as the first injection each animal received 0.05 ml of the 2.0 % suspension; in the 2nd to 10th injection 0.1 ml was applied per animal


B. CHALLENGE EXPOSURE
- Two weeks after 10th injection the challange-dose was given: 0.05 ml per animal
- At this time the control animals were injected with 0.05 ml of the 2.0 % suspension of the test sample


OTHER:
- shaving of treatment site: some days before starting the treatment the right flank of the animals was shaved with electric clippers; shaving was repeated before each injection and reading if necessary
- The reaction sites were examined 24 hours after the injection; diameter, colour, and thickness were used as criteria for the intensity of the reaction

Challenge controls:

Yes: control animals were injected with 0.05 ml of the 2.0 % suspension of the test sample at challenge exposure.

Positive control substance(s):

no

Results and discussion

Positive control results:

Not applicable

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Group:

test chemical

Dose level:

0.05 ml of 2 % solution of test substance in 0.85 % saline

No. with + reactions:

0

Total no. in group:

8

Clinical observations:

Not reported

Remarks on result:

other: Reading: 1st reading. Group: test group. Dose level: 0.05 ml of 2 % solution of test substance in 0.85 % saline. No with. + reactions: 0.0. Total no. in groups: 8.0. Clinical observations: Not reported.

Results 2

Reading:

1st reading

Group:

negative control

Dose level:

0.05 ml of 2 % solution of test substance in 0.85 % saline

No. with + reactions:

1

Total no. in group:

8

Clinical observations:

Reaction to injection at the same time as the challenge

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. Group: negative control. Dose level: 0.05 ml of 2 % solution of test substance in 0.85 % saline. No with. + reactions: 1.0. Total no. in groups: 8.0. Clinical observations: Reaction to injection at the same time as the challenge.

Results 3

Group:

positive control

Remarks on result:

not measured/tested

Any other information on results incl. tables

Table 1: Individual positive reactions (marked with + signs) observed during the induction and challenge period with Dicyandiamid EH

Test animals												Control animals
No.	Individual direct reaction										Challenge	No.	Reaction to injection at the same time as the challenge
	1	2	3	4	5	6	7	8	9	10
1575					+		+	+	+			1583
1576					+		+		+			1584
1577		+	+	+	+	+	+		+			1585
1578					+		+					1586
1579					+	+	+	+	+			1587	+
1580						+	+	+		+		1588
1581		+			+		+					1589
1582					+		+					1590
	0	2	1	1	7	3	8	3	4	1	0		1

Degree of reaction: + = mild

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Conclusions:

Dicyandiamid EH is not sensitizing to male guinea pigs under the conditions of this test.

Executive summary:

The test substance was administered by intradermal injections following the Landsteiner/Draize method. Sixteen male albino guinea pigs, were divided into 2 groups (test and control). The test animals were treated repeatedly with a 2 % solution of the substance in 0.85 % saline. During the induction period the test animals received a total of 10 injections, 3 times weekly for 3.weeks. Two weeks after the 10th injection the challenge-dose was given in an amount of 0.05 ml per animal. The reaction sites were examined 24 hours after the injection.

Dicyandiamid EH caused positive skin reactions upon repeated intradermal injections in all test animals. The reaction was mild. None of the test animals reacted positively upon the challenge-dose. One out of 8 controls showed a positive mild reaction to injection at the same time as the challenge.

From these results it can be concluded that Dicyandiamid EH was not sensitizing under the conditions of this study.