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EC number: 222-695-1 | CAS number: 3576-88-3
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- March - August 2009
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study with GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: The Guidelines for the Testing of Chemicals (2004) 414, China.
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- other: HJ/T154-2004, "The Guidelines for the Hazard Evaluation of New Test Chemical Substances", China.
- Deviations:
- not specified
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2,2'-iminobis[4,6-diamino-1,3,5-triazine]
- EC Number:
- 222-695-1
- EC Name:
- 2,2'-iminobis[4,6-diamino-1,3,5-triazine]
- Cas Number:
- 3576-88-3
- Molecular formula:
- C6H9N11
- IUPAC Name:
- N~2~-(4,6-diamino-1,3,5-triazin-2-yl)-1,3,5-triazine-2,4,6-triamine
- Details on test material:
- Sample name: 2,2'-iminobis[4,6-diamino-1,3,5-triazine]
CAS No.:3576-88-3
Supplier: DSM Engineering Plastics.
Physical state: off-white powder
Sample storage: At normal room temperature and humidity in the lightproof sample storeroom
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: SHANGHAI SLAC LABORATORY ANIMAL CO. LTD
- Age at study initiation: 12 weeks old
- Weight at study initiation: males: 300-400g and females: 237-328g.
- Housing: Animals were housed individually in plastic cages (L46 xW31 xH20cm).
- Diet (ad libitum): Diet were provided by SUZHOU SHUANGSHI LABORATORY ANIMAL FEED SCIENCE CO.,LTD. Certification: Su (E) Sishengzi (2002) 006.
- Water (ad libitum): The quality level of drinking water is in accordance with the standard of national GB5749 (Standards for Drinking Water Quality).
- Acclimation period:
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25 °C
- Humidity (%): 40-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): alternating 12 h periods of light and darkness
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
0, 250, 500 and 1000 mg of test substance were weighed and dissolved in 1% CMC-Na to a
volume of 10 ml as each solution of negative control, low, middle and high dose groups.
2 mg of Dexon was dissolved in 10 ml distilled water as solution of the positive control group.
VEHICLE
- Amount of vehicle (if gavage): 1 mL/100 g BW - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: One male rat and two female rats
- Length of cohabitation: from the afternoon to the next morning
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- From day 6 to day 15 of gestation
- Frequency of treatment:
- Daily from day 6 to day 15 of gestation
- Duration of test:
- 19 days (All of female rats were executed one day prior to the expected day of
delivery, which was day 20 of gestation.)
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
250 mg/kg BW
Basis:
- Remarks:
- Doses / Concentrations:
500 mg/kg BW
Basis:
- Remarks:
- Doses / Concentrations:
1000 mg/kg BW
Basis:
- No. of animals per sex per dose:
- 20 pregnant female rats per dose.
- Control animals:
- yes, concurrent vehicle
- other: positive control: DEXON
- Details on study design:
- - Dose selection rationale:
Preliminary test before formal trial was performed to determine the high dose in the
teratogenicity test in rats. According to the LD50 (5000mg/kg bw) calculated from the acute
toxicity test and the NOAEL (500mg/kg) obtained from 28 days of short-term repeated toxicity
test, the dose of 1000mg/kg ( 1/5 LD50 ) was first selected and the non-pregnant female rats (n=20)
were gavaged (1ml/100 mg BW) for 10 days. The toxic signs and the death were observed daily till
the 15th day.
Results of preliminary test: Different degree toxic signs were seen and none females died,
which was permitted by the principle of dosage design (toxic reaction is allowed by the high
dose, but the mortality rate should not exceed 10%). Therefore, the high dose of 1000mg/kg (1/5
LD50) was started in formal test.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked in table 2 were included.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: every 3 days from the day 6 of gestation
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20 - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: Yes - Statistics:
- All the data were summarized and analyzed by statistical software SPSS13.0. The measured
data, such as fetus body weight, body length, tail length and placenta weight, were tested by
one-way ANOVA (Dunnett tests). The resorption and dead incidence of fetus were analyzed by
Ch2 tests based on the parent body as statistical unit. The enumeration data, such as the resorption
and the dead rate of fetus, the teratogenic rate of skeleton and soft tissue, were compared between
treated groups and the negative control group by the approach of binomial distribution based on
the fetus number as statistical unit. The dose will be regarded as the teratogenic effects if the
difference of total teratism rate or individual teratism rate between such dose group and the
negative control group was statistically significant.
Total teratism rate in each group (%) = the total number of viable fetus with teratism divided by the total
number of viable fetus in parent body of this group x 100 % (One teratism was counted while
more than one kind of malformation happening in the same viable fetus). Teratogenicity index =
LD50 of female animals/the minimum teratogenicity dosage.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Compared with the negative control group, 1000 mg/kg (high dose) of this chemical significantly inhibited the body weight gain of pregnant rats,
suggesting that it had maternal toxicity to a certain extent. The other two doses had no such remarkable effects, suggesting that this test
met the requirement of dosage design principle in teratogenicity study.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
The high, middle and low doses of this chemical didn't significantly effect embryogenesis (no induction on the
resorption and death of fetus) and the growth and development of the fetus (body weight, placenta
weight, body length and tail length, sex ratio, the formation of appearance and soft tissue as well as
the development of skeletal system).
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Compared with the negative control group, the positive reagent could inhibit the body weight gain of pregnant rats, inducing growth retardation of pregnant rats. In addition, Dexon could increase the resorption incidence of fetus in pregnant rats, reduce body weight, placenta weight, body length and tail length of fetus and induce the abnormality of appearance, skeleton and soft tissue of fetus obviously, indicating the establishment of the experiment methods in this study.
Applicant's summary and conclusion
- Conclusions:
- This teratogenicity test in SD rats indicated that the body weight gain of pregnant rat
by 1000mg/kg was reduced significantly, compared with that of the negative control, indicating that
2,2'-iminobis[4,6-diamino-1,3,5-triazine] (CAS No.:3576-88-3) had maternal toxicity to a certain
extent; NOAEL for maternal toxicity is 500 mg/kg.
No embryonic toxicity and teratogenicity were detected in this study. The teratogenic NOAEL was 1000mg/kg.
According to the assessment of HJ/T 154-2004, the result of the teratogenicity test in rats is negative. - Executive summary:
The teratogenicity test of 2,2'-iminobis[4,6-diamino-1,3,5-triazine] in rats was performed according to The Guidelines for the Testing of Chemicals (2004) 414.
Experimental Animals:
Sprague-Dawley (SD) rats: 3 months old, 260 sexual maturity and unmated females, 237-328g
of body weight and 120 males, 300-400g of body weight.
Experimental method:
Three different dose-level test groups of low, middle and high dosage, a negative control
group and a Dexon positive control group were set up in this test. The dosage of each test group
was 250 mg/kg, 500 mg/kg and 1000 mg/kg BW, respectively. 20 pregnant female rats were
assigned to each group. The day on which a vaginal plug or sperm were observed was counted as
day 0 of gestation. From day 6 to day 15 of gestation, 1ml/100g BW of test substance was
administered daily by gavage to rats in 3 different dose groups as well as control groups.
Clinical observations were recorded every day. From day 6 of gestation, rats were weighed every 3 days
during the dosing period.
All of female rats were executed one day prior to the expected day of delivery, which was day 20 of gestation.
Immediately after caesarean, the uteri were removed and gravid uteri were weighed.
Examination of uterine contents was counted: the number of corpora lutea, implantation, resorptions,
viable fetuses and embryonic or fetal deaths, etc.
The development of fetuses was recorded one by one: body weight, body length, tail length, gender etc.
Examination of teratogenicity of fetuses was performed later: their appearance, skeletal and soft tissue alterations.
Statistical software was applied to analyze all the data and results.
The maximum no observed adverse effect level (NOAEL) of teratogenicity test was obtained through statistical analysis.
Result and conclusion:
This teratogenicity test in SD rats indicated that the body weight gain of pregnant rat by 1000 mg/kg reduced significantly, compared with that of the negative control, indicating that 2,2'-iminobis[4,6-diamino-1,3,5-triazine] had maternal toxicity to a certain extent; NOAEL for maternal toxicity was 500 mg/kg.
No embryotoxicity and teratogenicity were detected in this study. The maximum teratogenic NOAEL was 1000 mg/kg. According to the assessment of HJ/T 154-2004, the result of the teratogenicity test in rats is negative.
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