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EC number: 209-813-7 | CAS number: 593-85-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
- 28 d repeated dose oral toxicity: NOAEL ≥ 300 mg/kg bw/day, OECD TG 407 28 d, gavage
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1999-08-20 to 1999-03-11
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: - OECD TG 407 compliant - GLP compliant
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- as at 27 July 1995
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Version / remarks:
- as at 30 September 1996
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Strain: Rats, Fischer, CDF(F344)/CRLBR, SPF
- Source: Charles River Wiga GmbH, D-97633 Sulzfeld, Germany
- Age at study initiation: ca. 6 weeks
- Weight at study initiation: Males: 131.1 ± 8.9 g; Females: 106.0 ± 8.8 g
- Fasting period before study: no
- Housing: single caging in Makrolon cages type III (39 cm x 23 cm x 18 cm); wire mesh lids, sanitation of the cages once a week; aspen wood chips, type "4 HV" (Finn Tapvei Oy, SF-73620 1 Kortteinen), autoclaved; bedding material changed weekly
- Diet (e.g. ad libitum): ad libitum, Altromin 1314 forte, gamma irradiated with 25 kGy 60Co, Altromin GmbH, D-32791 Lage
- Water (e.g. ad libitum): ad libitum, tap water, acidified with HC1 to pH 3, from an automatic watering system
- Acclimation period: 13 d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 44
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
- made freshly each day shortly before the administration to the animals by dissolution of test substance in deionised water
VEHICLE
- Justification for use and choice of vehicle (if other than water): water
- Concentration in vehicle: 3, 9.5, and 30 mg/mL
- Amount of vehicle (if gavage): 10mL/kg - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- HPLC-UV/Vis
- solutions of the test substance derivated for 2.5 hours at 110 °C (derivating reagent: 160 mg NaOH, 2.5 ml acetyl acetone, dissolved in 1000 ml methanol)
- System:
• Hewlett Packard 1050 system,
• Integrator HP3395
• Column: YMC-Pack ODS-A, 5 gm (150 x 6 mm), produced by YMC Co., Kyoto, Japan
• Temperature: ambient
• Flow: 1.0 mL/min
• Mobile phase: 10.2 g KH2PO4 , 250 mL acetonitrile and 2.5 mL triethylamine, ad 750 mL deionised water
• Injection volume: 20 µL
• Retention time: ca. 5 min
• Detection: UV detector set at 295 nm - Duration of treatment / exposure:
- 28 d, recovery groups kept further 16 d without treatment
- Frequency of treatment:
- 7 d/wk
- Remarks:
- Doses / Concentrations:
30, 95 and 300 mg/kg bw per day
Basis:
actual ingested - No. of animals per sex per dose:
- 10/sex at control and 300 mg/kg bw/day group, 5/sex at 30 and 95 mg/kg bw/day groups; 5/sex of control and high dose group were kept as recovery groups
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on pre-experiments; no toxicity signs in a 7 d dose range finding study at 50, 158 and 500 mg, but all animals died within 2 d at 1000 mg/kg without specific toxic effects or indications of target organ toxicity.
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: high dose group and controls
- Post-exposure recovery period in satellite groups: 16 d - Positive control:
- no
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations:
• general signs
• health status
• viability (twice daily)
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: d -1, 6, 13, 20, 27: all animals of all groups, d 34, 41: all animals of the recovery groups
- Detailed clinical observations checked in table 2 were included.
BODY WEIGHT: Yes
- Time schedule for examinations: d -6, d 1, 8, 15, 22, 28 (all groups) and on 29, 35 and 43 (recovery groups only)
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Time schedule for examinations: d -6, d 1-7, 7-21, 21-28 (all groups) and d 29- 35 and 35-43 (recovery groups only)
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: d 29 (all dose groups except recovery groups)
- Anaesthetic used for blood collection: Yes (ether)
- Animals fasted: Yes, over night
- How many animals: all animals of all dose groups except recovery groups
- Parameters checked in table 3 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: d 29 (all dose groups except recovery groups)
- Animals fasted: Yes, over night
- How many animals: all animals of all dose groups except recovery groups
- Parameters checked in table 3 were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: d 27
- Dose groups that were examined: all dose groups
- Battery of functions tested:
• behaviour, of the motor activities and sensory reactivity to different stimuli (acoustic, tactile, visual and proprioceptive) tested outside the home cage in a standard arena.
• eyelid and auricular reflexes (tactile and proprioceptive)
• acoustic reaction (clapping of hands)
• visual reactivity
• righting reflex
• forelimb grip strength
OTHER: - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 4), conducted on d 29 all dose groups except recovery groups and on d 44 for recovery groups
HISTOPATHOLOGY: Yes (see table 4), conducted on d 29 all dose groups except recovery groups and on d 44 for recovery groups - Other examinations:
- no
- Statistics:
- - Tests:
• Analysis of variance followed by the Scheffe test: all data with means and standard deviations determined, for comparison of more than two groups
• t-test: all data with means and standard deviations determined, for comparison of two groups only
• H-test of Kruskal and Wallis followed by the test of Nemenyi: counted events with scoring or in cases where the requirements for the analysis of variance were not fulfilled.
• Chi²-test: counted events
• Fisher's exact test: counted events, if the Chi2-Test was not applicable
- Results analysed separately for males and females; P = 0.05 chosen in each test; two tailed test were used. Groups K and KR and C and CR were treated separately for statistical analysis.
- Numerical data have been rounded for presentation, a manual recalculation therefore may yield slightly different results to those given in the tables. - Details on results:
- CLINICAL SIGNS AND MORTALITY
- small lesions (term "dermal wounds or crusts", single lesions with a size of less than 1 mm) on the skin of the tails noted in life in several dosed animals, significant differences in the incidence of these alterations present only in high dosed animals of both sexes compared to the controls
- alterations attributed to biting or scratching by the animals themselves, probably caused by local itching.
- only some indications of reduced well-being (raised fur) noted in high dosed animal
- incidental findings (chromodakryorrhoea, respiratory murmur) not attributed to the action of the test substance
- see table 7 for details
BODY WEIGHT AND WEIGHT GAIN
- body weights of the high dosed males significantly reduced from Day 15 onwards until the end of the recovery period
- no significant group differences nor a corresponding trend noted in body weights of high dose females
- see table 8 for details
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
- significantly less food consumption in the first 2-3 weeks of the study in high dose males
- no significant group differences nor a corresponding trend noted in body weights of high dose females
HAEMATOLOGY
- no significant or dose related group differences in haematology
CLINICAL CHEMISTRY
- no significant or dose related group differences in clinical chemistry.
NEUROBEHAVIOUR
- no significant differences between dosed groups and the controls or dose related trends noted at functional observations or in grip strength
ORGAN WEIGHTS
statistically significant differences relative to controls
- high dose males:
• decrease: in absolute brain weight after recovery, absolute heart weight after 28 d, heart weight relative to brain weight after 28 d,
• increase: in brain weight relative to bw, testes relative to bw after 28 d and after recovery, kidneys relative to bw after 28,
- high dose females:
• decrease: -
• increase: thymus absolute weight and relative to bw after recovery
- see table 9 for details
GROSS PATHOLOGY
- only known spontaneous changes without any dose relationship noted at necropsy
HISTOPATHOLOGY: NON-NEOPLASTIC
- no significant or dose related group differences noted histopathologically.
- skin of the tails, changed in life: histopathologically normal; indication for secondary irritation to scratching or nibbling rather than for primary dermal lesion - Dose descriptor:
- NOAEL
- Effect level:
- >= 300 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects no substance related adverse effects at highest dose.
- Critical effects observed:
- not specified
- Conclusions:
- Body weights and feed consumption were reduced in high dosed males compared to the control. However, the effects were reversible in the recovery group and body weight gain reduction was less than 10% at the end of the recovery period compared to control recovery males. Organ weight/body weight ratio was increased in brain, testis and kidneys of high dose group males, which was attributed to the reduced body weight gain. Histopathological alterations of the organs were not found and all organ weight effects showed high tendency of reversibility in the recovery group. In the majority of the males and female in high dose group dermal wounds were found on tails which cleared up completely during recovery period. Due to the high grade of effect reversibility in the recovery group no adverse effects (LOAEL) of the test substance could be determined.
Based on the results of this study, the "No observed adverse effect level" (NOAEL) is higher than or equal to 300 mg Guanidine carbonate per kg body weight and day in both sexes. - Executive summary:
Guanidine carbonate was tested in a 28 d repeated dose study in rats with application via the oral route according to OECD Guideline 407 and GLP. The test substance was administered as a solution in deionised water orally by gavage to 3 groups of 5 male and 5 female F344 rats each, once a day on 7 days per week for 28 consecutive days.
Doses used:
• Group A (low dose): 30 mg per kg body weight and day,
• Group B (mid dose): 95 mg per kg body weight and day,
• Group C (high dose): 300 mg per kg body weight and day.
An equally sized negative control group (group K) received deionised water, the vehicle for the test substance. The dose volume was uniformly 10 ml per kg body weight. In addition, two groups of 5 males and 5 females each, i.e. one high dose recovery group (group CR) and one control recovery group (group KR), were treated in the same way as their corresponding groups, but were kept then for further 14 days without test substance administration in an attempt to observe the reversibility, persistence or delayed onset of test substance induced lesions.
Investigations:
• Animal observations: once a day (plus a daily check for viability).
• Detailed clinical observations: once a week.
• Functional observations: once in the last week of the dosing period.
• Body weight: once a week.
• Feed consumption: for each week.
• Haematology: on Day 29 and on Day 44.
• Clinical biochemistry: on Day 29 and on Day 44.
• Necropsy with gross pathological examination: on Day 29 and on Day 44.
• Organ weight determination.
• Histopathological examination.
Results
• Mortality:
All animals survived until the scheduled termination.
• Animal observation, detailed clinical examination, functional tests:
Dermal alterations (tiny wounds or crusts) were noted occasionally on tails of animals in all dosed groups, but mainly in high dosed group males and females. This effect cleared up completely at the end of the recovery period. Except for this, only unspecific signs were noted.
• Body weights:
In high dosed males a significantly lower body weight was present from Day 15 on. The effect was reversible in the recovery group and body weight gain reduction was less than 10% at the end of the recovery period compared to control recovery males
No significant differences or dose related trends were noted in the body weights of the females.
• Feed consumption:
In high dosed males a significantly lower feed consumption was present from the start of dosing but recovered completely in the recovery group. No significant differences or dose related trends were noted in the feed consumption of the females.
• Haematology and clinical chemistry:
No significant differences were noted between any dosed group and the controls.
• Functional observations:
No significant differences were noted between any dosed group and the controls.
• Necropsy with gross pathological examination and histopathology:No treatment related alterations were noted. The altered skin areas of the tails were normal histopathologically.
• Organ weight determination:
Organ weight/body weight ratio was increased in brain, testis and kidneys of high dose group males, which was attributed to the reduced body weight gain. The effects showed high tendency of reversibility in the recovery animals.
Conclusion
Based on the results of this study, the "No observed adverse effect level" (NOAEL) is higher than or equal to 300 mg Guanidine carbonate per kg body weight and day in both sexes.
Reference
- Table 4: Survey of the daily observations in life.
finding |
Number of affected males/females in group |
|||||
mg/kg bw |
0 (d 27) |
0 recovery (d 41) |
30 (d 27) |
95 (d 27) |
300 (d 27) |
300 recovery (d 41) |
dermal wounds, crusts a |
0/0 |
0/0 |
0/1 |
1/0 |
5/5 |
0/0 |
(a) multiple, tiny erosions on the tails.
- Table 5: Mean body weights
Data are presented by mean, standard deviation (sd) and number of animals (n).
mg/kg bw |
para-meter |
body weight (g) on Days 22 |
|||||||
-6 |
1 |
8 |
15 |
22 |
28 |
35 |
43 |
||
Males |
|||||||||
0 |
mean |
131.2 |
167.2 |
193.6 |
213.6 |
232.8 |
242.8 |
- |
- |
|
sd |
7.9 |
6.9 |
6.1 |
6.3 |
7.3 |
9.4 |
|
|
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
|
0 recovery |
mean |
131.2 |
164.8 |
192.8 |
214.6 |
232.4 |
243.0 |
253.6 |
263.8 |
|
sd |
7.3 |
8.0 |
8.2 |
9.1 |
10.8 |
11.0 |
9.9 |
11.4 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
30 |
mean |
131.6 |
162.8 |
186.8 |
206.6 |
225.2 |
234.4 |
- |
- |
|
sd |
9.9 |
9.9 |
8.9 |
8.9 |
9.0 |
9.5 |
|
|
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
|
95 |
mean |
129.0 |
160.8 |
184.8 |
204.0 |
223.0 |
230.2 |
- |
- |
|
sd |
10.0 |
13.8 |
14.2 |
13.5 |
14.9 |
15.8 |
|
|
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
|
300 |
mean |
132.8 |
166.2 |
181.4 |
190.8* |
207.4* |
209.8* |
- |
- |
|
sd |
9.2 |
8.0 |
12.0 |
10.8 |
8.3 |
8.8 |
|
|
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
|
300 recovery |
mean |
130.6 |
164.2 |
175.8 |
191.6* |
208.4* |
216.6* |
226.6* |
239.6* |
|
sd |
8.2 |
14.1 |
14.9 |
8.5 |
11.0 |
12.3 |
13.0 |
10.8 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Females |
|||||||||
0 |
mean |
107.2 |
123.4 |
133.0 |
140.8 |
149.0 |
151.0 |
- |
- |
|
sd |
7.9 |
6.9 |
6.1 |
6.3 |
7.3 |
9.4 |
|
|
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
|
0 recovery |
mean |
106.0 |
124.6 |
134.0 |
143.0 |
149.6 |
152.8 |
159.0 |
160.2 |
|
sd |
7.3 |
8.0 |
8.2 |
9.1 |
10.8 |
11.0 |
9.9 |
11.4 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
30 |
mean |
105.1 |
121.2 |
130.8 |
139.0 |
146.0 |
150.6 |
- |
- |
|
sd |
9.9 |
9.9 |
8.9 |
8.9 |
9.0 |
9.5 |
|
|
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
|
95 |
mean |
106.2 |
123.2 |
134.0 |
143.4 |
150.4 |
154.8 |
- |
- |
|
sd |
10.0 |
13.8 |
14.2 |
13.5 |
14.9 |
15.8 |
|
|
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
|
300 |
mean |
105.3 |
121.4 |
131.2 |
136.8 |
143.6 |
147.0 |
- |
- |
|
sd |
9.2 |
8.0 |
12.0 |
10.8 |
8.3 |
8.8 |
|
|
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
|
300 recovery |
mean |
106.3 |
124.6 |
134.0 |
139.4 |
148.0 |
152.2 |
159.2 |
161.2 |
|
sd |
8.2 |
14.1 |
14.9 |
8.5 |
11.0 |
12.3 |
13.0 |
10.8 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
* Significant differences to the control
for Table 6 see under "Overall remarks, attachments" (this is only necessary due to space limitations in this field)
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 300 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- - OECD TG 407 compliant
- GLP compliant
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Oral repeated dose toxicity
Guanidine carbonate was tested in a 28 d repeated dose study in rats with application via the oral route (gavage) at doses of 30, 95 and 300 mg/kg bw/d conducted according to OECD TG 407 and GLP.
Body weights and feed consumption were reduced in high dosed males compared to the control. However, the effects were reversible in the recovery group and body weight gain reduction was less than 10 % at the end of the recovery period compared to control recovery males. Organ weight/body weight ratio was increased in brain, testis and kidneys of high dose group males, which was attributed to the reduced body weight gain. Histopathological alterations of the organs were not found and all organ weight effects showed high tendency of reversibility in the recovery group. In the majority of the males and female in high dose group dermal wounds were found on tails which cleared up completely during recovery period. Due to the high grade of effect reversibility in the recovery group no adverse effects (LOAEL) of the test substance could be determined.
Based on the results of this study, the "No observed adverse effect level" (NOAEL) is ≥ 300 mg Guanidine carbonate per kg body weight and day in both sexes.
Inhalation repeated dose toxicity
No inhalation repeated dose toxicity studies are available.
Dermal repeated dose toxicity
No dermal repeated dose toxicity studies are available.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
A GLP study performed in accordance with OECD TG 407 is available and was chosen as the key study.
Justification for classification or non-classification
Based on the results of the study the substance does not need to be classified according to CLP (Regulation (EC) No 1272/2008).
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