Cyanamide

Endpoint summary

Description of key information

Technical active cyanamide (hydrogen cyanamide/ L500, a 50% aqueous solution) was examined in two acute oral studies, one acute dermal toxicity study and in one acute inhalation toxicity study.

The obtained results (LD50 values) were extrapolated for the pure active cyanamide (Cyanamid F1000) and were considered to be moderately toxic via the oral (LD50: 142 mg/kg bw/d) and the dermal (LD50: 848 mg/kg bw/d) route and practically not toxic via the inhalation route (LC50 >1 mg/L).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1973

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Applied volume was not constant. Body weight determination only at day 1 and at termination.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

From the following 5% (v/v) aqueous dilutions: 4, 5, 6, 7 mL/kg bw, the following dose test substance were applied respectively: 0.2, 0.25, 0.3, 0.35 mL/kg bw.

Doses:

100, 125, 150, 175 mg/kg bw of cyanamide

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Only at day 1 and at termination
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Preliminary study:

The dose selection was based upon a range-finding study using groups of one to five male and female rat/test group: undiluted technical cyanamide was dosed at 1.0, 2.0 or 5.0 mL/kg bw followed by dosages of 4.0, 6.0 and 8.0 mL of a 10 % (v/v) aqueous dilution (corresponding to 0.4, 0.6 and 0.8 mL test substance/kg bw). Mortality was seen in all rats dosed with 0.6 mL test substance/kg bw or more shortly after dosing with signs of convulsion. All females rats dosed with 0.4 mL/kg bw survived while all males of this dose group died. Clinical signs were lachrymation, apnoea and coma.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

142 mg/kg bw

Based on:

act. ingr.

Mortality:

Mortality was observed in all dose levels with a higher incidence in males and occurred mainly during the first day between 6 and 24 hours after dosing. One male died on the third post treatment day.

Clinical signs:

other: The only clinical symptoms were convulsions in rats, that died. Rats, that survived, had no significant changes at necropsy.

Gross pathology:

Rats, that survived, had no significant changes at necropsy.

Other findings:

No other findings

Males			Females
Dose	Mortality	Time of death	Dose	Mortality	Time of death
100 mg/kg	1/5	Day 1	100 mg/kg	0/5	-
125 mg/kg	4/5	Day 1	125 mg/kg	0/5	-
150 mg/kg	5/5	Day 1 and 3	150 mg/kg	2/5	Day 1
175 mg/kg	5/5	Day 1	175 mg/kg	1/5	Day 1

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral LD50 of pure active substance cyanamide in rats was estimated to be 142 mg/kg bw for the sexes combined.

Executive summary:

Cyanamid L500 (supplied as 50 % aqueous solution) was orally administered in a 5 % (v/v) aqueous dilution to four groups of Albino Wistar rats (source not mentioned), each group with five males and five females, at dose levels of 100 to 175 mg/kg bw by gavage.

The animals were observed for treatment-related effects during the first 4 hours and for a subsequent 14-day observation period.

Mortality was observed in all dose levels with a higher incidence in males and occurred mainly during the first day between 6 and 24 hours after dosing. One male died on the third post treatment day.The only clinical symptoms were convulsions in rats, that died. Rats, that survived, had no significant changes at necropsy.

The acute oral LD50 of pure active substance cyanamide in rats was estimated to be 142 mg/kg bw for male and female rats (ca.300 mg/kg bw of the 50% aquous solution).

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

142 mg/kg bw

Quality of whole database:

2 GLP and guideline studies available

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Report deficiencies: E.g. temperature of air, humidity of air, equipment for measuring temperature, humidity and particulate aerosol. No data of body weight, individual clinical signs and gross pathological findings.

Principles of method if other than guideline:

Some minor report deficiencies which are considered to have no impact on the quality of the results:
e.g. temperature of air, humidity of air, equipment for measuring temperature, humidity and particulate aerosol. No data of body weight, individual clinical signs and gross pathological findings.

GLP compliance:

no

Remarks:

The study was conducted prior to implementation of GLP.

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Central Institute for the Breeding of Laboratory Animals TNO, Zeist, Netherlands
- Body weight at the study initiation was about 200 g for males and about 180 g for females

Route of administration:

other: Inhalation: mists

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

2.0 mg/ L of technical active Cyanamid L500

No. of animals per sex per dose:

5 animals per sex per dose (one dose)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 mg/L air

Exp. duration:

4 h

Remarks on result:

other: Corresponding to technical active Cyanamid L500 > 2.0 mg/L.

Mortality:

No mortalities were recorded during the study.

Clinical signs:

other: During the exposure a lumback behaviour and a rapid shallow respiration with frequent coughing and swallowing were observed. Within a few hours after exposure all animals were completely recovered and showed normal behaviour.

Body weight:

Not indicated

Gross pathology:

No visible lesions were observed at gross necropsy.

Other findings:

No other findings

Interpretation of results:

GHS criteria not met

Conclusions:

The inhalative LC50 of cyanamide was > 1 mg/L in male and female rats after 4 hour inhalation (corresponding to technical active Cyanamid L500 > 2.0 mg/L).

Executive summary:

The toxicity of Cyanamid L500 (a 50 % aqueous solution) by the inhalation route (whole-body) was investigated in five male and five female Wistar rats. The rats were exposed to the mist of technical active cyanamide in a concentration of 2.0 mg/L of air (corresponding to the highest technical attainable concentration) for four hours.

No mortalities were recorded during the study. During the exposure a lumback behaviour and a rapid shallow respiration with frequent coughing and swallowing were observed. Within a few hours after exposure all animals were completely recovered and showed normal behaviour. No visible lesions were observed at gross necropsy.

The inhalative LC50 of cyanamide was > 1 mg/L in male and female rats after 4 hour inhalation (corresponding to technical active Cyanamid L500 > 2.0 mg/L).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

1 000 mg/m³ air

Physical form:

inhalation: dust / mist

Quality of whole database:

Only one GLP and guideline compliant study available.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: U.S. EPA 40 CFR Part 158.81.2

Deviations:

not applicable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

The New Zealand White Rabbits were provided by Hazelton Research Products Inc., Denver Pennsylvania.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The test substance was applied dermally to the shaved intact skin (approximately 10 % of the total body surface) of the test animals. The liquid test material was held in contact with the skin for a 24 hour period with impervious rubber damming.

Duration of exposure:

24 h

Doses:

530, 1060 and 2120 mg/kg bw of pure active substance Cyanamide, corresponding to 1.0, 2.0 and 4.0 mL/kg bw of 50 % aqueous Hydrogen cyanamide solution.

No. of animals per sex per dose:

5 animals per dose per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Sex:

male

Dose descriptor:

LD50

Effect level:

901 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: Corresponding to 1.7 mL/kg bw of the 50 % aqueous Hydrogen cyanamide solution.

Sex:

female

Dose descriptor:

LD50

Effect level:

742 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: Corresponding to 1.4 mL/kg bw of the 50 % aqueous Hydrogen cyanamide solution.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

848 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: Corresponding to 1.6 mL/kg bw of the 50 % aqueous Hydrogen cyanamide solution.

Mortality:

Mortality was observed in all dose groups, especially at mid (1060 mg/kg bw ) and high dose (2120 mg/kg bw) levels and occurred between day 1 and day 2 after treatment. No clinical observations were noted at the mid dose as all animals died on day 1.

Clinical signs:

other: Clinical signs of toxicology included tremors, ataxia, anorexia, depression and were observed at the low and high dose group. No signs of dermal irritations were noted in the low dose group, whereas all surviving animals of the high dose group showed a we

Gross pathology:

In rabbits that survived no pathologic changes at necropsy were observed. In rabbits found dead during the observation period changes mainly concerning the lung were observed (dark red lungs or dark red lung areas). In one animal of the high dose group a pale liver was noted.

Other findings:

No other findings

Table 1: Mortality in the acute dermal toxicity study in White rabbits with cyanamide

Males			Females
Dose	Mortality	Time of death	Dose	Mortality	Time of death
530 mg/kg bw	0/5	-	530 mg /kg bw	1/5	Day 1
1060 mg/kg bw	5/5	Day 1 and 2	1060 mg/kg bw	5/5	Day 2
2120 mg/kg bw	4/5	Day 2	2120 mg/kg bw	5/5	Day 2

 

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute dermal LD50 was 901 mg/kg bw in males, 742 mg/kg bw in females and 848 mg/kg bw combined for the sexes pure active substance cyanamide in rabbits (corresponding to about 1.6 mL/kg bw for the sexes combined, 1.7 mL/kg bw for males and 1.4 mL/kg bw for females of the 50 % aqueous Hydrogen cyanamide solution).

Executive summary:

The test substance Cyanamid L500 was applied dermally to the shaved intact skin of five male and five female New Zealand White rabbits per dose group. 50 % w/w hydrogen cyanamide technical solution 1.0, 2.0 and 4.0 mL/kg bw (corresponding to 530, 1060 and 2120 mg/kg bw pure active substance cyanamide) were applied. The liquid test material was held in contact with the skin for a 24 hour period with impervious rubber damming. The animals were evaluated for treatment related effects on the day of dosing and for a subsequent 14-day observation period.

Clinical signs included tremors, ataxia, anorexia, depression were observed at the low and high dose group. No signs of dermal irritations were noted in the low dose group, whereas all surviving animals of the high dose group showed a well defined erythema and a very slightly oedema on day 1. All other animals died before primary dermal irritation scoring could be performed. In rabbits that survived no pathologic changes at necropsy were observed. In rabbits found dead during the observation period changes mainly concerning the lung were observed (dark red lungs or dark red lung areas). In one animal of the high dose group a pale liver was noted.

The acute dermal LD50 was 901 mg/kg bw in males, 742 mg/kg bw in females and 848 mg/kg bw combined for the sexes pure active substance cyanamide in rabbits (corresponding to about 1.6 mL/kg bw for the sexes combined, 1.7 mL/kg bw for males and 1.4 mL/kg bw for females of the 50 % aqueous Hydrogen cyanamide solution).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

848 mg/kg bw

Quality of whole database:

Only one GLP and guideline compliant study available.

Additional information

Oral Toxicity:

Two acute oral toxicity studies were conducted, examining the effects of application of different concentrations of technical cyanamide (Cyanamid L500, a 50% aqueous solution) in a single treatment in male and female wistar rats.

In the key study (Engel, 1973, Doc. No. 521-001) the acute oral LD50 was determined to be 284 mg/kg bw technical cyanamide (equivalent to 142 mg/kg bw pure active cyanamide) for sexes combined. Mortality mainly occurred during the first day after administration.

In the supporting study an oral LD50 of 446 mg/kg bw technical active cyanamide (equivalent to 223 mg/kg bw pure active cyanamide) for sexes combined was obtained from a newer study (Daamen, 1994, Doc. No. 521-002) which was carried out in accordance to the recent OECD 401 guideline and under GLP. Signs of intoxication included lethargy, hunched posture, uncoordinated movements, tremors, piloerection and breathing difficulties. Macroscopic post mortem examination of the animals that died during the study revealed above all changes in the digestive tract (haemorrhages, thickened areas). In addition, haemorrhages in lungs and other organs were observed.

 

Dermal Toxicity:

In an acute dermal toxicity study (Osheroff, 1988, Doc. No. 522-002) which was performed in New Zealand White rabbits a LD50 of 1696 mg/kg bw of technical active ingredient cyanamide (corresponding to 848 mg /kg bw of pure active cyanamide) combined for the sexes was determined. The LD50 determination was based on the observed mortality pattern in this study. In rabbits that survived no pathologic changes at necroscopy were observed. In rabbits found dead during the observation period changes mainly concerning the lungs were observed.

 

Inhalation Toxicity:

In an acute inhalation (whole-body) toxicity study, Wistar male and female rats were exposed to mist of technical active cyanamide in a concentration of 2.0 mg/L (corresponding to the highest technical attainable concentration) for 4 hours. The animals were observed for 14 days. No mortality and no severe injury occured. Therefore the inhalative LC50 of technical active cyanamide was determined to be > 2 mg/L in male and female rats, corresponding to pure active cyanamide > 1.0 mg/L.

Justification for selection of acute toxicity – oral endpoint
GLP and guideline compliant study.

Justification for selection of acute toxicity – inhalation endpoint
GLP and guideline compliant study

Justification for selection of acute toxicity – dermal endpoint
GLP and guideline compliant study

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.

 

Oral Toxicity:

Based on the results of the acute oral toxicity studies (LD50 of 142 mg/kg bw of the pure active cyanamide) the test substance is classified as category 3 for acute oral toxic effects and labelled as H301 (toxic if swallowed) according to the Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.

 

Dermal Toxicity:

Based on the results of the acute toxicity dermal study (848 mg/kg bw of pure active cyanamide) cyanamide is classified as category 3 for acute dermal toxicity and labelled H311 (toxic in contact with skin) according to the Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.

 

The classification for oral and dermal acute toxicity is in accordance with the conclusion of the 33 RAC-Meeting (1-5 June 2015, Helsinki).

 

Inhalation Toxicity:

Cyanamide is not classified for acute inhalation toxicity based on the obtained LD50 (1 mg/L pure active cyanamide) which was technically the highest attainable concentration, according to the Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.