Cyanamide

Endpoint summary

Description of key information

Skin:
One study (van Beek, 1982) is available for Cyanamid F1000. From the results of this study, it is concluded that SKW-Cyanamid F1000 is a severe primary skin irritant and that is corrosive to the skin of albino rabbits when brought into contact with the skin for four hours as necrotic damage to the skin was still observed 1 week after treatment.
Additional studies with aqueous solutions of Cyanamid L500 (1, 5, 25% or 49-50%), showed that Cyanamid L500 causes severe skin irritation in New Zealand White rabbits.

 

Eye:
As Cyanamid F1000 is classified as skin corrosive, no eye irritation study with Cyanamid F1000 has to be conducted. Results of the two available eye irritation studies with aqueous Cyanamid L500 solutions in New Zealnd White rabbits showed that the Cyanamid L500 is irritating to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The observation time points were not in accordance with the requirements of the OECD guideline 404.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

skin reactions were scored at 4 and 52 hours after end of exposure instead of 24, 48 and 72 hours. Skin irritation study should not performed with abraded skin.

GLP compliance:

no

Remarks:

the study follows the recommendations of OECD guideline 404 broadly.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No more details were indicated

Type of coverage:

semiocclusive

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL of the undiluted test substance.

Duration of treatment / exposure:

4 hours

Observation period:

Approximately 4 hours after bandage removal and 52 hours after dosing.

Number of animals:

6 animals

Details on study design:

Twenty four hours prior to the test substance application the hair is removed from the back of the animals with electrical clippers in such a way as to avoid abrasions. An amount of 0.5 g of the test substance is brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. The patches are fixed to the application site by means of adhesive tape and the entire trunk of the rabbits is wrapped with an impervious material to maintain the rest patches in position and to retard evaporation of volatile substances. Each rabbit is treated on the intact and abraded skin. The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding. Effects of dermal irritation were recorded, at approximately 4 hours after bandage removal and 52 hours after dosing. The skin reactions are evaluated by the method of Draize.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(1016)

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(1017)

Time point:

24/48/72 h

Score:

2.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(1018)

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

(1019)

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

erythema score

Basis:

animal #5

Remarks:

( 1020)

Time point:

24/48/72 h

Score:

3.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

erythema score

Basis:

animal #6

Remarks:

(1021)

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(1016)

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(1017)

Time point:

24/48/72 h

Score:

2.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(1018)

Time point:

24/48/72 h

Score:

2.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

edema score

Basis:

animal #4

Remarks:

(1019)

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

edema score

Basis:

animal #5

Remarks:

(1020)

Time point:

24/48/72 h

Score:

2.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

edema score

Basis:

animal #6

Remarks:

(1021)

Time point:

24/48/72 h

Score:

1.5

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2.8

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

The score is the mean value of results at 4 and 52 h (results obtained from a treated animal with intact and not abraded skin).

Irritant / corrosive response data:

The dermal effects observed , were as follows:
- after 4 hours: very slight to moderate erythema, focal haemorrhages and slight or moderate edema;
- after 52 hours: well-defined to moderate erythema, slight ischemia, very slight incrustation and very slight edema. The treated skin areas had a purple colour suggesting the presence of haemorrhages.
After one week the greater part of the treated skin areas showed slight to distinct necrosis.

Other effects:

No other effects

Table 1: Individual and average skin irritation scores of SKW Cyanamid F1000

 

rabbit number	intact skin		rabit number	abraded skin
	4 hours	52 hours		4 hours	52 hours
	A B	A B		A B	AB
1016	4-3	4-1	1016	2-3	4-1
1017	2-3	3-2	1017	2-3	3-1
1018	4-3	4-2	1018	2-3	4-1
1019	4-3	4-1	1019	2-3	4-1
1020	3-3	4-2	1020	4-3	3-1
1021	1-2	3-1	1021	2-3	2-1
average	5.8	5.2	average	5.3	4.3

A = erythma

B = edema

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

From the present results it is concluded that SKW Cyanamid F1000 is a severe primary skin irritant and that it is corrosive to the skin of albino rabbits when brought into contact with the skin for four hours as necrotic damage to the skin was still observed 1 week after treatment.

Executive summary:

0.5 g of the test substance was applied to the intact or abraded skin of six New Zealand White rabbits. The application sites were covered with gauze bandaging secured with several wrappings of adhesive tape and provided semi-occlusive dressing. Approximately 4 hours after dosing the bandages and the test substance were removed. Dermal readings were taken at approximately 4 hours after bandage removal and 52 hours after dosing.

The observations showed that after 4 hours: very slight to moderate erythema, focal haemorrhages and slight or moderate edema. After 52 hours: well-defined to moderate erythema, slight ischemia, very slight incrustation and very slight edema were observed. The treated skin areas had a purple colour suggesting the presence of haemorrhages. After one week the greater part of the treated skin areas showed slight to distinct necrosis, therefore it can be concluded according to the CLP/GHS regulations that SKW Cyanamid F1000 is a severe primary skin irritant and that it is corrosive to the skin of albino rabbits when brought into contact with the skin for four hours.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Foxfields Rabbits; Petersfield, Hampshire, England
- Body weight and age: Body weight 3 kg, approximately 14 weeks old

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

A single dose of 0.1 mL of the test substance

Duration of treatment / exposure:

Not indicated

Observation period (in vivo):

Examination of the eye was made 1 hour as well as 1, 2, 3, 4 and 7 day after the end of exposure.

Number of animals or in vitro replicates:

1 rabbit

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 96 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

7 d

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 48, 72 hours

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 96 hours

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 96, 7 days

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

: redness

Basis:

animal #1

Time point:

other: 1, 24, 48, 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: At 48 and 72 hours also an haemorrhage of the nictating membrane was observed.

Irritation parameter:

conjunctivae score

Remarks:

: redness

Basis:

animal #1

Time point:

other: 96 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: An haemorrhage of the nictating membrane was also observed.

Irritation parameter:

conjunctivae score

Remarks:

: redness

Basis:

animal #1

Time point:

other: 7 days

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1, 24 hours

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 48, 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 96 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 7 days

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

: redness

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Irritant / corrosive response data:

One hour after the end of exposure the cornea was dull and by the following day an opacity had developed which persisted for the following three days and resolved seven days after instillation. Iritis was observed two and three days after the end of exposure. A diffuse conjunctiva redness was accompanied by swelling, the lids half closed and a copious discharge.

Other effects:

There was also evidence of haemorrhage on the nictating membrane.

Table 1: Results of the primary eye irritation test in a rabbit with cyanamide:

Time	Cornea	Iris	Conjunctiva
			redness	chemosis	discharge
1 hour	D*	0	2	3	3
24 hours	2	0	2	3	3
48 hours	2	1	2^+	2	2
72 hours	2	1	2^+	2	2
96 hours	1	0	1^+	1	1
7 days	0	0	0	0	0
mean scores 24-72 h	2	0.67	2	2.3

D = Dulling of the cornea

⁺haemorrhage of nictating membrane

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Cyanamide was found to be an eye irritant to one New Zealand white rabbit under the test conditions.

Executive summary:

The test substance, Cyanamid L500 (supplied as aqueous solution) was applied in a single dose of a 0.1 mL aliquot into the lower everted lid of one eye of an adult New Zealand white rabbit (body weight 3 kg, 14 weeks old). The contralateral eye remained untreated and served as a control. Examination of the eye was made 1 hour as well as 1, 2, 3, 4 and 7 day after the end of exposure. The animal was observed daily for clinical signs and behaviour.

One hour after the end of exposure the cornea was dull and by the following day an opacity had developed which persisted for the following three days and resolved seven days after instillation. Iritis was observed two and three days after the end of exposure. A diffuse conjunctiva redness was accompanied by swelling with the lids half closed and a copious discharge. There was also evidence of haemorrhage on the nictating membrane. All lesions had resolved seven days after the end of exposure. The mean scores (24- 72 hours) for the examined parameters were as follows: Cornea:2, iris: 0.67, conjunctiva redness: 2, chemosis: 2.3.

Due to the severity of the reaction no further animals were exposed to the test substance.

Under the test conditions the test substance examined in a rabbit can be considered as an eye irritant.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

One study (van Beek, 1982) is available for Cyanamid F1000. In this study, 0.5 g of the test substance was applied to the intact or abraded skin of six New Zealand White rabbits. The application sites were covered with gauze bandaging secured with several wrappings of adhesive tape and provided semi-occlusive dressing. Approximately 4 hours after dosing the bandages and the test substance were removed. Dermal readings were taken at approximately 4 hours after bandage removal and 52 hours after dosing. The observations showed that after 4 hours: very slight to moderate erythema, focal haemorrhages and slight or moderate edema. After 52 hours: well-defined to moderate erythema, slight ischemia, very slight incrustation and very slight edema were observed. The treated skin areas had a purple colour suggesting the presence of haemorrhages. After one week the greater part of the treated skin areas showed slight to distinct necrosis, therefore it can be concluded according to the CLP/GHS regulations that KW-Cyanamid F1000 is a severe primary skin irritant and that it is corrosive to the skin of albino rabbits when brought into contact with the skin for four hours.

 

The skin irritation potential of Cyanamid L500 (50% of aqueous dilution of cyanamide) was investigated in three available studies performed with New Zealand White rabbits. The results (Van Beek, 1984, Doc. No.565-004) indicated that cyanamide at concentrations > 25 % caused severe irritancy based on findings after removal of the patches after a 4 hour exposure period. However, the cyanamide dilutions of 1 and 5 % did not show a skin irritating effect. The average scores (24, 48, 72 h) for erythema were 0.5, 0.6 and 1.2 for the 1%, 5%, 25% cyanamide solution respectively and the average oedema scores were 0.06, 0.06 and 0.2 for the 1%, 5%, 25% cyanamide solution. In another study of van Beek (1982, Doc. No. 565-001) skin irritation findings were also observed after 4 and 52 hours after application. In the contrary to these two studies the study of Ligget (1989, Doc. No. 565-002) exhibited no significant skin irritation findings (erythema average score after 24, 48,72 h of 0.11 and oedema of 0.0).

 

 

Eyes

As Cyanamid F1000 is classified as skin corrosive, no eye irritation study with Cyanamid F1000 has to be conducted. Cyanamid F1000 is thus considered to cause severe eye irritation.

Available studies with Cyanamid L500 on eye irritation: New Zealand white rabbits were treated with Cyanamid L500 (50% w/w aqueous hydrogen cyanamide solution) in the study of van Beek (1974, Doc. No. 566-001). The treatment resulted in slight corneal opacity, mild iritis, moderate redness and moderate swelling of the conjunctiva in all animals. One week after treatment some recovery was observed, however, all animals still suffered from slight conjunctivitis. The mean scores (24-72 h) were as follows: Cornea: 1.1, iris: 0.9, conjunctiva-redness: 1.9, conjunctiva-chemosis: 2.3. An aqueous cyanamide solution was re-examined to assess eye irritation potential in the rabbit (Ligget, 1991, Doc. No. 566-002). This treatment resulted in severe inflammatory reactions lasting for 7 days. Due to the level of reactions, no further animals were exposed to the test substance. The mean scores (24-72 h) were as follows: Cornea: 2.0, iris: 0.67, conjunctiva-redness: 2.0, conjunctiva-chemosis: 2.3).

Justification for selection of skin irritation / corrosion endpoint:
Guideline compliant study with the pure substance.

Justification for selection of eye irritation endpoint:
GLP and guideline compliant study.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

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 skin corrosion (van Beek, 1982), the test item Cyanamid F1000 is classified as skin corrosive category 1B and severely eye damaging, and labelled with H314 (causes severe skin burns and eye damage) according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.

 

According to the conclusion of the 33 RAC-Meeting (1-5 June 2015, Helsinki), the substance should be classified as skin corrosive cat. 1, but a subcategorisation is intended under Regulation (EC) No 1272/2008, as amended for the eighteenth time in Regulation (EU) 2022/692, and the available data allow classification into cat 1B.