Cyanoguanidine

Endpoint summary

Description of key information

Two oral acute toxicity studies similar to OECD 401 but with a low level of documentation and no specifications of the

test compound are available. Both indicate DCD to be practical nontoxic in rats. One inhalation study similar to OECD 403 shows DCD to be practical nontoxic in rats when applied at the highest achievable concentration of 259 mg/m3 for 4h. One dermal acute toxicity limit test equivalent to OECD 402 shows no toxic effect in rabbits at a limit dose of in 2000 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:

weight of evidence

Study period:

1982

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: gavage

Vehicle:

other: edible oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 2 ml
- total exposure duration: 1 and 5 days, respectively

Doses:

- 7 g/kg body weight (Stomach tube, single treatment)
- 1 g/kg body weight (stomach tube, treatment for five consecutive days)

No. of animals per sex per dose:

- 7 g/kg dose group: three rats were used, sex not specified
- 1 g/kg dose groupfive rats were used, sex not specified

Control animals:

no

Details on study design:

No details reported

Statistics:

No statistics reported

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 7 000 mg/kg bw

Mortality:

No

Clinical signs:

other: - 7 g/kg dose group: no harmful effects, except for a slight weight loss during treatment, were observed on any rats. - 1 g/kg dose group: no clinical signs

Gross pathology:

No data

Other findings:

No data

Interpretation of results:

GHS criteria not met

Conclusions:

Dicyandiamide is practically nontoxic when administered orally in rats at doses of 1 g/kg bw (treatment for 5 consecutive days) and 7 g/kg bw (single dose).

Executive summary:

In an acute oral toxicity study, groups of 3 and 5 rats were given oral doses of Dicyandiamide at 7000 mg/kg (vehicle: peanut oil) bw and 1000 mg/kg bw (vehicle: edible oil), respectively. The 7000 mg/kg bw dose was administered as one single dose. Rats which received the 1000 mg/kg bw dose were treated for 5 consecutive days.

No harmful effects, except for a slight weight loss during treatment in the 7000 mg/kg bw dose group, were observed on any rats.

 Oral LD₀      > 7000  mg/kg bw

 

Dicyandiamide is practically nontoxic based on the LD₀ in rats.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1977

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Central Institute for Nutrition and Food Research
- Age at study initiation: young adults
- Weight at study initiation: males: 204-240 g; females: 85-125 g
- Fasting period before study: yes (overnight)
- Housing: screen-bottomed stainless steel cages in a well-ventilated room
- Diet: stock diet ad libitum
- Water: tap water ad libitum



ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-25

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 33 % (w/v)
- Amount of vehicle (if gavage): 30 ml/kg bw (equivalent to 10 g test material/kg bw)

Doses:

10 g/kg body weight

No. of animals per sex per dose:

10 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Statistics:

The LD50 was calculated according to th emethod of Weil (Bioetrics 8 (1952) 249-263).

Preliminary study:

No data

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Mortality:

No deaths occurred.

Clinical signs:

other: Within a few hours after treatment the rats showed sluggishness and humpback behaviour. Slight diarrhoea was frequently observed. These phenomena had dissappeared after 20 hours. The rats looked quite healthy during the rest of the observation period.

Gross pathology:

Macroscopic examinations of the survivors at autopsy did not revea any treatment-related gross alterations.

Other findings:

No other findings reported.

Interpretation of results:

GHS criteria not met

Conclusions:

Dicyandiamide is practically nontoxic when administered orally in rats at a dose of 10 g/kg bw.

Executive summary:

In an acute oral toxicity study (similar to OECD 401, limit test), groups of 10 fasted young adult albino rats (Wistar) of both sexes (10 animals per group) were given Dicyandiamide as 33 % aqueous suspension at a single dose of 10000 mg/kg bw and observed for 14 days.

Oral LD50: Males > 10000 mg/kg bw; Females > 10000 mg/kg bw

All animals survived to the scheduled sacrifice. There were no in-life observations indicating treatment related systemic effects. At necropsy, no deviations from normal morphology were found in all animals. Dicyandiamide is practically non-toxic based on the LD50 in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

January - November 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

no information on body weight changes, no raw data reported

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Age at study initiation: 8 weeks
- Weight at study initiation: males ca. 195 g, females ca. 131 g
- Diet (e.g. ad libitum): stock diet
- Water (e.g. ad libitum): tap water
- Housing: wire screen cages
- observation period: 14 days

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 1.5 m³
- Method of holding animals in test chamber: animals were housed in wire screen cages
- Source and rate of air: filtered air, flow rate: 1m³/h
- System of generating particulates/aerosols: the powder was continuously dispersed in air by means of a "Wright" Dust Feed Mechanism at a rate of 6g/m³


TEST ATMOSPHERE
- Brief description of analytical method used: particle size determinations and counts were carried out in samples taken from the atmosphere in the chamber with a cascade impactor
- Particle size distribution: 99 % particke size range of 0.6 - 2.4 µm
- Concentration in air: 259 mg/m³ (maximum attainable concentration)
- Determination of concentration: gravimetrically by passing measured amounts of chamber air through glass fibre filters

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Determination of concentration: gravimetrically by passing measured amounts of chamber air through glass fibre filters

Duration of exposure:

4 h

Concentrations:

259 mg/m³ (maximum attainable concentration)

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
- Other examinations performed: mortality, signs of intoxication

Statistics:

No data.

Key result

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 259 mg/m³ air

Exp. duration:

4 h

Mortality:

Mortality did not ocur either during exposure or during the subsequent 14-day observation period.

Clinical signs:

other: Signs of intoxication did not ocur either during exposure or during the subsequent 14-day observation period.

Body weight:

No data.

Gross pathology:

No data.

Other findings:

Other observations:
During the first quarter of an hour of the exposure period the rats showed slight restlessness; during the remaining part of the exposure period they were asleep.

Interpretation of results:

GHS criteria not met

Conclusions:

As a four-hour exposure of rats to a dispersion of Dicyandiamid at a maximum attainable concentration of 259 mg/m³ of air did not cause mortality or any noticeable deleterious effects, it can be concluded that the powder has a very low acute inhalation toxicity. It is not likely, therefore, that the substance at concentrations up to 259 mg/m³ will present acute inhalation hazard to man.

Executive summary:

The aim of this study was to determine the 4 -hour LC₅₀ value of Dicyandiamid. Each five male and female rats were exposed to the test atmosphere generated by dispersing the powder continuously in air by means of a "Wright" Dust Feed Mechanism at a rate of 6 g/m³ for four hours (whole-body exposure) at an actual concentration of 259 mg/m³ (maximum attainable concentration).

The animals were observed for mortality and signs of intixication during exposure and daily thereafter for 14 days. Particle determination and counts in air samples revealed a 99 % particle size range of 0.6 - 2.4 µm.

The four-hour exposure of the rats to a dispersion of Dicyandiamid at a maximum attainable concentration of 259 mg/m³ of air did not cause mortality or any noticeable deleterious effects, it can be concluded that the powder has a very low acute inhalation toxicity. It is not likely, therefore, that the substance at concentrations up to 259 mg/m³ will present acute inhalation hazard to man.

The acute inhalation (4 hour) LC₅₀ for Dicyandiamid in the rat is higher than 259 mg/m³.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

259 mg/m³ air

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:

December 1984 - January 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazelton Dutchland, Inc., Denver, Pennsylvania
- Weight at study initiation: males: 2099 - 2454 g; females: 2093 - 2446 g
- Housing: individually in elevated wire-mesh cages
- Diet (ad libitum): commercial rabbit ration (Purina Lab Rabbit Chow)
- Water (ad libitum): tap water
- Acclimation period: minimum -> one week prior to initiation of treatment

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back of rabbits, hair was closely clipped; skin was left intact
- Type of wrap if used: nonabsorbent binder composed of rubber damming


REMOVAL OF TEST SUBSTANCE
- Washing (if done): exposure sites were wiped with water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes
- For solids, paste formed: no

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations for signs of toxic and pharmacologic effects: immediately after dosing, at one and four hours postdose, and once daily thereafter for fourteen consecutive days; mortality/moribundity was recorded twice daily
- Individual body weights were recorded prior to treatment, on Day 7 and at death or termination
- Necropsy of survivors performed: yes
- Other examinations performed: dermal responses were graded and scored on Days 1, 3, 7, 10, and 14 according to the system of Draize (1959)

Statistics:

No data

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occured during the study.

Clinical signs:

other: All animals appeared normal throughout the study.

Gross pathology:

No observable gross pathology was noted in any animal at necropsy.

Other findings:

Dermal Irritation:
- Slight erythema (Grade 1) was noted in one male at day 1.
- All others appeared normal.

Table 1: Individual Body Weights, Acute Dermal Toxicity Study in Rabbits, 2000 mg/kg

Animal Number	Body Weight - Grams
	Initiation	Day 7	Day 14
Males
E37343	2445	2636	2830
E37344	2267	2449	2650
E37345	2454	2747	2870
E37346	2374	2717	2710
E37347	2099	2150	2300
Females
E37407	2120	2185	2370
E37408	2321	2287	2375
E37409	2446	2730	2960
E37410	2093	2132	2360
E37411	2446	2634	2480

 

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 was estimated to be greater than 2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study, groups of New Zealand White rabbits (5 animals per sex) were dermally exposed to Dicyandiamide for 24 hours at a dose of 2000 mg/kg bw (limit test).  Animals then were observed for 14 days.

Dermal LD50: males > 2000 mg/kg bw; females > 2000 mg/kg bw; combined > 2000 mg/kg bw

No mortality occurred during the study. All animals occurred normal throughout the study. Slight erythema (Grade 1) occurred in one male on Day 1. All others appeared normal. No observable gross pathology was noted in any animal at necropsy. Dicyandimaid is relatively harmless based on the results of this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Two acute oral toxicity studies reported with a low level of documentation and no specifications of the test compound indicate DCD to be practical nontoxic in rats (LD0 = 7 g/kg bw; 10 g/kg bw). This finding is supported by a reliable inhalation study at the highest technically attainable concentration of 259 mg/m³. DCD shows no signs of toxicity in a dermal acute toxicity limit test at 2 g/kg bw.

These data meet the requirements of the REACH regulation. DCD is considered to be practical non-toxic in acute toxicity tests.

Justification for classification or non-classification

No mortalities or clinical signs were observed at appropriate dose levels.