Cyanamide

Endpoint summary

Description of key information

Two separate studies in guinea pigs examined the dermal sensitisation potential of cyanamide. In the key study a SKW Cyanamid F1000 (pure active ingredient) was examined according to the Magnusson-Kligman method while the other study examined the dermal sensitisation of an aqueous solution of cyanamide (53 % w/v) according to the method of Buehler. Results of the key study showed distinct skin sensitisation properties whereas the study conducted with the aqueous solution showed an ambiguous result, indicating that cyanamide may have skin sensitization properties.

This result was supported by case reports in which men and women exhibited inflammatory skin conditions after contact with cyanamide in different formulations.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The study was conducted before the LLNA-method became the standard in vivo-method for evaluation of the skin sensitising potential of a substance. Furthermore, the in vitro methods had not been established as sufficient methods to replace animal testing.

Species:

guinea pig

Strain:

not specified

Sex:

male

Details on test animals and environmental conditions:

- Source: Central Institute for the breeding of Laboratory animals TNO; Netherlands

Route:

intradermal and epicutaneous

Vehicle:

water

Concentration / amount:

1% and 2.5% dilution of Cyanamid F1000

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

1% and 2.5% dilution of Cyanamid F1000

Day(s)/duration:

24 and 48 h

No. of animals per dose:

10 Guinea pigs per dose (per test group) and 5 Guinea pigs in each control group

Details on study design:

- The dermal sensitisation potential of SKW Cyanamid F1000 (pure active substance) was evaluated in the Guinea Pig Maximisation Test (GPMT) according to the method of Magnusson and Kligman in 15 male albino guinea pigs. Approximately 24 and 48 hours after the challenge phase, the test sites were evaluated for signs of elicited sensitisation. The same procedures were carried out on a contemporaneous control group, where the test articles were replaced by water (vehicle control).
Intradermal induction was performed with 10% (v/v) cyanamide in water. A dermal induction was performed one week after intradermal induction with 5% (w/w) cyanamide in vaseline. Dermal challenge was done two weeks after dermal induction with 1% (w/w) cyanamide in vaseline (left flank) and with 2.5% (w/w) cyanamide in vaseline (right flank).

Challenge controls:

- 5 challenge control animals were treated (only during the challenge exposure) with 2.5% dilution of the test substance and 5 challenge control animals were treated (only during the challenge exposure) with 1% dilution of the test substance.

Positive control substance(s):

no

Positive control results:

No positive control

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1% Cyanamid F1000

No. with + reactions:

8

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1% Cyanamid F1000. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: none.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1% Cyanamid F1000

No. with + reactions:

7

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1% Cyanamid F1000 . No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: none.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

1% Cyanamid F1000

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: other: Negative control (received only challenge treatment with 1% Cyanamid F1000). Dose level: 1% Cyanamid F1000. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

1% Cyanamid F1000

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: see Remark

Remarks:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: Negative control (received only challenge treatment with 1% Cyanamid F1000). Dose level: 1% Cyanamid F1000. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

2.5% Cyanamid F1000

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2.5% Cyanamid F1000. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: none.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

2.5% Cyanamid F1000

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2.5% Cyanamid F1000. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: none.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

2.5% Cyanamid F1000

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other:

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: other: Negative control (received only challenge treatment with 2.5% Cyanamid F1000). Dose level: 2.5% Cyanamid F1000. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

2.5% Cyanamid F1000

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other:

Remarks:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: Negative control (received only challenge treatment with 2.5% Cyanamid F1000). Dose level: 2.5% Cyanamid F1000. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Group:

positive control

Remarks on result:

other: no positive control

- Induction:

The intradermal injection caused slight erythema and abscesses in all test animals. The dermal applications induced slight erythema in four out of ten test animals.

The challenge treatment of the left flank (1 % dilution) provoked slight to moderate erythema in all test animals. The erythema was visible immediately after removal of the dressing. At the same time one of the control animals reacted slight positive. After 24 and 48 hours most of the test animals still showed slight to moderate erythema. None of the control animals showed a positive reaction at this time. No test substance-related clinical signs of toxicity were observed.

All ten test animals challenged with 2.5 % dilution of the test substance showed well-defined to severe erythema immediately after removing of the dressing. At the same time one of the control animals reacted slight positive. After 24 and 48 hours the test animals still showed clear positive reactions. None of the control animals showed a positive reaction at this time. No test substance-related clinical signs of toxicity were observed.

 

Table 1: Results in the Buehler test of Cyanamide in males:

Control group animals	24 h after patch removal	48 h after patch removal	Test group animal	24 h after patch removal	48 h after patch removal
1	0/0	0/0	1	0/0	0/0
2	0/0	0/0	2	0/0	0/0
3	0/0	0/0	3	0/0	0/0
4	0/0	0/0	4	0/0	0/0
5	0/0	0/0	5	0/0	0/0
6	0/0	0/0	6	0/0	0/0
7	0/0	0/0	7	0/0	0/0
8	0/0	0/0	8	0/0	0/0
9	0/0	0/0	9	1/0	not applicable
10	0/0	0/0	10	1/0	not applicable

Score: grade of erythema/oedema

 

Table 2: Results in the Buehler test of cyanamide in females:

Control group animals	24 h after patch removal	48 h after patch removal	Test group animal	24 h after patch removal	48 h after patch removal
1	0/0	0/0	1	1/0	not applicable
2	0/0	0/0	2	0/0	0/0
3	0/0	0/0	3	0/0	0/0
4	0/0	0/0	4	0/0	0/0
5	0/0	0/0	5	0/0	0/0
6	0/0	0/0	6	1/0	not applicable
7	0/0	0/0	7	0/0	0/0
8	0/0	0/0	8	0/0	0/0
9	0/0	0/0	9	0/0	0/0
10	0/0	0/0	10	0/0	0/0

 

 

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

Based on the results of the Guinea Pig Maximisation Test (GPMT) according to the method of Magnusson and Kligman the active substance Hydrogen cyanamide is a sensitiser.

Executive summary:

The dermal sensitisation potential of SKW Cyanamid F1000 (pure active substance) was evaluated in the Guinea Pig Maximisation Test (GPMT) according to the method of Magnusson and Kligman in 15 male albino guinea pigs. Approximately 24 and 48 hours after the challenge phase, the test sites were evaluated for signs of elicited sensitisation. The same procedures were carried out on a contemporaneous control group, where the test article was replaced by water (vehicle control).

 

Induction: The intradermal injection caused slight erythema and abscesses in all test animals. The dermal applications induced slight erythema in four out of ten test animals. The challenge treatment of the left flank (1 % dilution) provoked slight to moderate erythema in all test animals. The erythema was visible immediately after removal of the dressing. At the same time one of the control animals reacted slight positive. After 24 and 48 hours most of the test animals still showed slight to moderate erythema. None of the control animals showed a positive reaction at this time. No test substance-related clinical signs of toxicity were observed.

All ten test animals challenged with 2.5 % dilution of the test substance showed well-defined to severe erythema immediately after removing of the dressing. At the same time one of the control animals reacted slight positive. After 24 and 48 hours the test animals still showed clear positive reactions. None of the control animals showed a positive reaction at this time. No test substance-related clinical signs of toxicity were observed.

 

Based on the results of the Guinea Pig Maximisation Test (GPMT) according to the method of Magnusson and Kligman the active substance Hydrogen cyanamide is a sensitiser.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Two available studies investigated the skin sensitising potential of cyanamide. The dermal sensitisation potential of SKW Cyanamid F1000 (pure active ingredient) was evaluated by the Magnusson-Kligman method. All test animals showed a positive response in the challenge test with the 2.5 % dilution after 24 and 48 hours after patch removal. Sensitising properties were also observed in most animals treated with the 1 % concentration. According to the classification by Magnusson and Kligman, cyanamide is considered to have distinct sensitising properties. In another study an aqueous solution of cyanamide (53 % w/v) was used to evaluate the sensitising potential in guinea pigs according to the method of Buehler. Under the conditions described in the study cyanamide induced some positive skin reactions after the challenge application (4/20). However, histological examination revealed in one of these animals severe irritating effect. The study provided a borderline result, thus, according to the study cyanamide may have skin sensitisation properties.

 

Sensitisation data in humans (case reports) which are documented in IUCLID in section 7.10.4 imply of a sensitisation potential of hydrogen cyanamide in humans who had contact with aqueous solution of cyanamide mostly due to their occupational backgroud (Conde-Salazar et al., 1981; Calnan, 1970; De Corres and Lejarazu, 1982; Bujan et al., 1994). On the other side, examinations of employees from the cyanamide production unit SKW Trostberg AG did not show any case of confirmed or suspected allergy towards hydrogen cyanamide, even though these persons were exposed. Therefore, it can be concluded that the sensitising potential of hydrogen cyanamide is low and under practical conditions it is very unlikely to occur.

Nevertheless, on the basis of the two available animal studies, the test substance, cyanamide, is classified as a category 1 substance for inducing skin sensitisation.

 

Summary of results:

Species	Method	Number of animals sensitised/total number of animals	Result	Reference
Guinea pig	The study follows to a great extent OECD guideline 406 Guinea Pig Maximisation Test	1% 8/10 2.5 % 10/10	sensitising	Til et al., 1982 Doc. No. 567-003
Guinea pig	OECD 406 (1981); EEC 92/69- B6 Buehler test	4/20	Not sensitising	Mercier, 1988 Doc. No. 567-001

Justification for selection of skin sensitisation endpoint:
GLP and guideline compliant study with the pure substance.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Based on experience in handling and use the substance cyanamide is not regarded as sensitising to the respiratory system (occupational health safety control).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on sensitisation properties of Cyanamid F1000, the test item was classified and labelled as a skin sensitiser as skin sensitiser Cat. 1 (H317: May cause an allergic skin reaction) according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.

This classification is in accordance with the conclusion of the 33 RAC-Meeting (1-5 June, 2015), Helsiniki.