Potassium cyanate

Endpoint summary

Description of key information

Oral route

The LD50 of potassium cyanate after oral administration to rats was determined to be 567 mg/kg bw for females and 936 mg/kg bw for males.

Dermal route

The acute dermal LD50 value of the test item potassium cyanate proved to be greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Other routes

The LD50 of potassium cyanate after i.p. administration to mice was determined to be 320 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984-06-14 to 1984-07-11

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

not applicable

Principles of method if other than guideline:

- Bliss, C.J., the statistics of bioassay academic press, New York, 1962
- Finney, D.J., Probit analysis, 2nd ed., Cambridge Univ. Press, Cambridge 1952
- Hunter, W.J.; Lingk, W.; Recht, P.: Intercomparison study on the determination of single administration toxicity in rats; Commission of the European communities, Heath and Safety Directorate, j. Assoc. Off. Anal. Chem. 62, 864 - 873, 1979
- Weber, E., Grundriß d. biol. Statistik, G. Fischer- Verlag, Stuttgart, 7. Auflage, 1972

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

weight: male 158 -199 g; female 129 -177 g
age: male 55 - 62 days; female 63 - 73 days

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

A aqueous solution was prepared with a concentration of 100 mg/mL.
The volume of application was 4.64 - 10.0 mL/kg for male and for female resulting in 464 - 1000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Duration of observation period following administration: 14 days
- Frequency of observations: 30 min, 1, 2, 4, 8, 24 hours as well as on day 2 and thereafter daily
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

567 mg/kg bw

Based on:

test mat.

95% CL:

>= 216 - <= 1 487

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

936 mg/kg bw

Based on:

test mat.

95% CL:

>= 278 - <= 3 151

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

464 mg/kg bw

Based on:

test mat.

Mortality:

The deaths occurred between 20 minutes and 4 hours after application.

Clinical signs:

other: The symptoms of poisoning were disorders of central nervous system, decrease of tonicity and loss of startle reflexes. Additional disorders of coordination of action, severe shiver and severe clonical convulsions was showed. Furthermore, tonic convulsions

Gross pathology:

not indicated

Other findings:

Macroscopic post mortem examination of the animals did not reveal any abnormalities.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 value for potassium cyanate was determined to be 567 mg/kg bw in female rats and 936 mg/kg bw in male rats.

Executive summary:

In an acute oral toxicity study, groups of 55 to 73 days old Wistar rats (5/sex) were given a single oral dose of potassium cyanate (98 %.) in water at doses of 464 - 1000 mg/kg bw.

The acute oral LD50 value was determined to be 567 mg/kg bw in females and 936 mg/kg bw in males. The LD0 value for both sexes was 464 mg/kg bw.

The symptoms of poisoning were disorders of central nervous system, decrease of tonicity and loss of startle reflexes. Additional disorders of coordination of action, severe shiver and severe clonic convulsions was showed. Furthermore, tonic convulsions, arduous breathing and breathlessness were showed.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1967

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

not applicable

Principles of method if other than guideline:

After 18 hour without feed, KOCN was administered once to the animals per gavage. The animals were monitored 28 days. 5 doses were administered.

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

body weight: 180 - 200 g

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

NA

Doses:

5

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 28 days
- Other examinations performed: food consumption, body weight,organ weights, behaviour

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

2 360 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 970 - <= 2 840

Mortality:

The deaths were observed within 10 -30 minutes after administration.

Clinical signs:

other: The animals were sedated with the reconvalescence phase.

Gross pathology:

not indicated

Other findings:

not indicated

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute oral LD50 value was determined to 2360 mg/kg bw in rats orally exposed to the test item.

Executive summary:

In an acute oral toxicity study, groups of Wistar rats (5/sex) were given a single oral dose of potassium cyanate in water at 5 different doses.

The death was observed within 10 - 30 minutes after administration.

The acute oral LD50 value was determined to be 2360 mg/kg bw in Wistar rats.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1996

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

no guideline followed

Principles of method if other than guideline:

Mice were given orally the test item.

GLP compliance:

not specified

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not indicated.

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

not indicated.

Doses:

not indicated.

No. of animals per sex per dose:

not indicated.

Control animals:

not specified

Details on study design:

not indicated.

Statistics:

not indicated.

Preliminary study:

not indicated.

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

841 mg/kg bw

Based on:

test mat.

Mortality:

not indicated.

Clinical signs:

other: not indicated.

Gross pathology:

not indicated.

Other findings:

not indicated.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The mouse LD50 value after oral administration was determined to be 841 mg/kg bw.

Executive summary:

In an acute oral toxicity study mice were given orally doses of potassium cyanate. The acute oral LD50 value was determined to be 841 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

567 mg/kg bw

Quality of whole database:

The study is comparable to guideline and the documentation is sufficient for assessment.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

other:

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:

2009-10-05 to 2009-11-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkez u. 90
- Age at study initiation: 8 weeks
- Weight at study initiation: males: 244 - 267 g; females. 22 - 233 g
- Fasting period before study: not stated
- Housing: during acclimatisation: 3 animals/sex/cage; during the study: animals were housed individually in type-II polypropylene/polycarbonate cages
- Diet: ssniff SM/ R/m-Z + H complete diet; producer: ssniff Spezialdiäten GmbH, D-59494 Soest, Germany; ad libitum
- Water: tap water from watering bottles; ad libitum
- Acclimation period: 9 days

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 10 % area of the total body surface
- % coverage: 10%
- Type of wrap if used: Sterile gauze pads were placed on the skin of rats. These gauzes were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was wrapped with semi-occlusive plastic wrap.

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 24 h

TEST MATERIAL
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males; 5 females

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

Statistics:

LD50 determination

Preliminary study:

none

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred after the 24-hour dermal exposure to potassium cyanate in Crl:(WI)BR male and female rats during the study.

Clinical signs:

other: No behavioural changes or general systemic toxic signs were noted during the study. Similarly, no any local symptoms (dermal irritation) were observed on the treated skin of animals as redness and oedema.

Gross pathology:

No macroscopic alterations due to the effects of the test item were found.

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions, the acute dermal LD50 value of the test item potassium cyanate proved to be greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Executive summary:

An acute dermal toxicity study was performed with test item potassium cyanate in Crl:(WI)BR rats, in compliance with OECD Guideline No. 402 and Commission Regulation (EC) 440/2008 of 30 May 2008 B.3.

A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to potassium cyanate at 2000 mg/kg bw by dermal route.

The test item was applied in original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

No mortality occurred during the study. Neither male nor female animals treated at 2000 mg/kg bw showed behavioural changes and no general toxic signs were noted during the study.

The test item did not cause any dermal irritation symptoms.

The body weight development was undisturbed both in male and female animals.

No macroscopic alterations of organs and tissues referred to the toxic effect of the test item were seen during the necropsy.

Under the experimental conditions, the acute dermal LD50 value of the test item potassium cyanate proved to be greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Study according to Guideline and in compliance with GLP.

Additional information

Acute oral toxicity

Key study

In an acute oral toxicity study equivalent to EU method B.1, groups of 55 to 73 days old Wistar rats (5/sex) were given a single oral dose of potassium cyanate (98 %.) in water at doses of 464 - 1000 mg/kg bw.

The acute oral LD50 value was determined to 936 mg/kg bw (males) and 567 mg/kg bw (females). The LD0 value was 464 mg/kg bw for both sexes.

The symptoms of poisoning were disorders of central nervous system, decrease of tonicity and loss of startle reflexes. Additional disorders of coordination of action, severe shiver and severe clonical convulsions was showed. Furthermore, tonic convulsions, arduous breathing and breathlessness were showed.

Supporting studies

In an acute oral toxicity study equivalent to EU method B.1, groups of Wistar rats (5/sex) were given a single oral dose of potassium cyanate in water at 5 different doses. The death was observed within 10 - 30 minutes. The acute oral LD50 value was determined to be 2360 mg/kg bw.

In a second supporting study, groups of mice were given orally doses of potassium cyanate. The acute oral LD50 value was determined to be 841 mg/kg bw.

Acute dermal toxicity

An acute dermal toxicity study was performed with potassium cyanate in Crl:(WI)BR rats, in compliance with OECD Guideline No. 402 and Commission Regulation (EC) 440/2008 of 30 May 2008 B.3.

A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to potassium cyanate at 2000 mg/kg bw by dermal route.

The test item was applied in original form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

No mortality occurred during the study. Neither male nor female animals treated at 2000 mg/kg bw showed behavioural changes and no general toxic signs were noted during the study. The test item did not cause any dermal irritation symptoms. The body weight development was undisturbed both in male and female animals.

No macroscopic alterations of organs and tissues referred to the toxic effect of the test item were seen during the necropsy. Under the experimental conditions, the acute dermal LD50 value of the test item potassium cyanate proved to be greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Other routes:

In an acute toxicity study (i.p. administration), groups of B6/D2 F1 mice were given increasing doses of potassium cyanate. The LD50 value was determined to be 320 mg/kg bw after intraperitoneally adminstration.

After the administration of a lethal dose, the mice appeared sedated, but then suddenly developed seizures which could be triggered by noise. Some animals recovered from several of these seizures, but eventually succumbed. The deaths after a lethal dose occurred within 15 minutes to one hour after the injection; mice that survived an LD50 dose recovered from the sedation and did not appear permanently affected.

Justification for classification or non-classification

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

Based on the available experimental data, the test item is considered to be classified for acute oral toxicity category 4 and labelled with H302 (Harmful if swallowed) under Regulation (EC) No 1272/2008, as amended for the seventeenth time in Regulation (EU) 2021/849.

Based on the available experimental data, the test item is not considered to be classified for acute dermal toxicity under Regulation (EC) No 1272/2008, as amended for the seventeenth time in Regulation (EU) 2021/849.