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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

Referenceopen allclose all

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:
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 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:
- 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
Body weight:
- 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 data
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.

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:
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 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:
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.
Body weight:
Not examined.
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:
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 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

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:
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 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:
All animals appeared normal throughout the study.
Body weight:
Most animals gained weight from initiation through termination (see table 1).
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.