Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 221-070-0 | CAS number: 2997-92-4
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 10.07.-25.09.2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- 2,2'-azobis[2-methylpropionamidine] dihydrochloride
- EC Number:
- 221-070-0
- EC Name:
- 2,2'-azobis[2-methylpropionamidine] dihydrochloride
- Cas Number:
- 2997-92-4
- Molecular formula:
- C8H18N6.2ClH
- IUPAC Name:
- 2,2'-diazene-1,2-diylbis(2-methylpropanimidamide) dihydrochloride
- Reference substance name:
- 2,2'-azobis(2-amidinopropane)-dihydrochloride
- IUPAC Name:
- 2,2'-azobis(2-amidinopropane)-dihydrochloride
- Test material form:
- other: granules
- Details on test material:
- - Name of test material (as cited in study report): 2,2'-azobis(2-amidinopropane)-dihydrochloride
- Substance type: organic
- Physical state: solid
- Analytical purity: 99.1 %
- Lot/batch No.: I59596
- Expiration date of the lot/batch: 31. Dec. 2012
- Storage condition of test material: ambient temperature, dark
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- other: Wister HAN (IGS)
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- Males were dosed daily for 43 - 50 days including the scheduled termination of the in-life phase. This included two weeks of dosing prior to mating and continued throughout the mating period until approximately four weeks post-mating.
Females were dosed two weeks prior to mating, covering at least two complete oestrous cycles, the variable time to conception, the duration of pregnancy and at least four days after delivery, up to and including the day before scheduled termination of the in-life phase. Therefore the duration of the study following acclimatisation depended on the female performance and was at least 48 days:
14 days pre-mating, up to 14 days until mating, an average of 21 days of gestation, and between 9 and 12 days of lactation. - Frequency of treatment:
- daily
- Details on study schedule:
- During acclimatisation and pre-mating, male rates were caged in groups of three animals per cage; females were housed individually. Throughout the mating period, animals were kept in pairs of one female and one male rat. The female was placed with the same male until pregnancy occured or two weeks had eclapsed. In case a male died during the mating period or succesfully mating was not detectable after 14 days, re-mating of females with proven males (sires) of the same group was considered. Each morning, the females were examined for the presence of a vaginal plug or sperm. Day 0 of pregnancy was defined as the day a vaginal plug or sperm was found. After the mating period, male rats were kept in groups of three at maximum; female rates were kept single.
Dams with offspring were sacrified between days 9 and 12 post-partum. The day of birthwas defined as day 0 post-partum. Females that showed no evidence of copulation were re-mated with proven sires. Dosing was continued in both sexes during the mating period.
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
Basis:
nominal conc.
60 mg/kg Bw
- Remarks:
- Doses / Concentrations:
Basis:
nominal conc.
20 mg/kg Bw
- Remarks:
- Doses / Concentrations:
Basis:
nominal conc.
6,7 mg/kg Bw
- No. of animals per sex per dose:
- 12 animals per sex per dose
- Control animals:
- yes
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weight male: mild effects in the high dose
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Body weight male: mild effects in the high dose
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 60 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
Effect levels (F1)
- Key result
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Regarding the reproduction and development parameters gathered in this study no changes were obsered in all experimental groups that were definitely test item related.
During first and second mating phase, no apparent differences occured regarding the evidence of copulation and the number of females that achieved pregnancy. On two occasions, couples were separated due to an increase body weight of the female animals although no evidence for copulation was detected. All other females conceived within the first five days. Pregnancy lasted 21 days, 22 days, or 23 days. Four female animals of the high dose group delivered one or two stillbirth, as well as two females of the low dose group and three femals of the vehicle control group. None stillbirth was deformed or had developmental delay.
Two animals gave birth to their litters on day 18 of gestation phase. The high dose animal gave birth to one stillbirth. All other pups were of normal size and appearance, thus it could be assumed that sperm plug on day one or two of the mating phase was missed (couples were separated without sperm plug on day 9 or 7 of the mating phase.
No difference between the dose groups were detectable regardin g the number of dams with both, live young born at day zero (d0, day of birth and alive pups at day four (d4) of lactation. The mean numbers per dam of corpora lutea, implantations and live pups at d0 and d4 as well as the mean litter weight at d0 and d4 were normal for Wistar rats, and no statistically significant differences between the dose group were found. Stillbirth (n=11) were distributed rather homogenously among all dose groups.
On day 4pp one pup of an animal of the medium dose group had lost its right leg from the knee downwards. Apart from that, the pup was in a good condition until the end of the in-life phase. As the amnimal waas unobtrusive on day 0pp it could be assumed that an injury was casual for the loss. None of the other animals had pups showing abnormalities that could be related to the test item.
The loss of offspring (pre-implantation, pre-natal or post-natal) were normal for primiparae rats of this strain and age. Although slightly
higher mean values regarding the pre-implantation losses could be observed for the test item treated animals when compared to the vehicle control animals, no test item related tendency could be observed.
No further abnormalities were detected during gestation and lactation phase. In summary, no differences were observed regarding reproduction sucess (achievement of pregnancy after indication of copulation, litter size and survival of pups) for all test item related animals when compared to the vehicle control animals.
Applicant's summary and conclusion
- Conclusions:
- The parental NOAEL of reproductive toxicity was considered to be 60 mg/kg/day for male and female rats.
- Executive summary:
In the present study oral uptake of the test item at a dose of 60 mg/kg body weight did not induce toxic effects on the development and the reproduction of Wistar rats.
Mild discomfort throughout the whole application period was observed for the animals treated with the high and the medium dose of the test item (salivation after application, blending of mucous membranes at nose and mouth, respirators sound) . A biological and particularly toxicological relevance of those observation could not be substantiated due to the sporatic incidence of the symptoms.
In comparison to the vehicle control group significant decreased body weight values were determined for the male animals treated with the high dose of the test item during week 4 whereas no conspicuities regarding body weight were observed for the male animals treated with the medium and the low dose. Similarly, no significant differences were observed between all female test item treated animals and the respective vehicle control animals.
A tendency of slightly enhanced amounts for water consumption within the test item treated male animals could observed throughout the whole in-life phse whereas no differences were detected for the female animals. An impact of the test item administration on the food consumption could not be observed, neither for male nor for female animals.
The most prevalent findings during necrospy were swollen lymph nodes. All other findings were observed with low incidences and without any test item related tendency. They were thus regarded to be spontaneous in nature.
Histopathological examination of the ovaries as well as of the epididymides/testes did not produce any evidence ot pathomorphological findings that are considered to be due to a toxic effect of the test item.
Regarding the reproduction and development parameters gatherd in this stud no changes were observed that were definitely treatment related. reproduction success (achievment of pregnancy after the indication of copulation, litter size and survival rate of pups) was comparable between test item related animals and the vehicle control group.
A daily oral administration of the test item to male Wister rats at dose level of 6,7 mg, 20 mg and 60 mg/kg body weight over a time period of 43 to 50days did not produce any pathological evidence to toxic effects on the reproduction performance of male rats. However, effects of the spermatogenesis may not have had an adequate time to become evident (such as reduced sperm counts affecting the fertility) as chemical exposure does not cover a complete cycle of spermatogenesis in male test animals.
A daily oral administration of the test item to female Wistar rats at dose levels of 6,7 mg, 20 mg and 60mg/kg body weight over a time period of 48 to 68 days did not produce any pathological evidence for toxic effects on reproduction preformance of female rats.
With respect to the results the NOAEL of the test item under the study conditons was estimated to be 60 mg/kg body weight. So far, no adverse effect has been observed regarding the reproduction of female and male rats. Nonetheless, due to the selectivity of the end points and the short duration of the study the data ascertained in this study do not indicate absolute safety with respect to the reproduction and development.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.