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EC number: 236-740-8 | CAS number: 13472-08-7
- 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

Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment. GLP guideline study with acceptable restrictions. Restrictions : no english data on study design, no details on functional observational battery tests.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 999
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2,2'-dimethyl-2,2'-azodipropiononitrile
- EC Number:
- 201-132-3
- EC Name:
- 2,2'-dimethyl-2,2'-azodipropiononitrile
- Cas Number:
- 78-67-1
- Molecular formula:
- C8H12N4
- IUPAC Name:
- 2,2'-diazene-1,2-diylbis(2-methylpropanenitrile)
- Details on test material:
- - Name of test material (as cited in study report): 2,2'-AZOBIS(2-METHYLPROPIONITRILE)
- Physical state: white crystal
- Analytical purity: 99.9%
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Storage condition of test material: no data
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Not available in English language
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- Not available in English language
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Males were exposed for 42 days.
Females were exposed from 14 days prior to mating to day 3 of lactation.
Terminal killing at day 43 for males and on day 4 of lactation for females. - Frequency of treatment:
- No English data
Doses / concentrations
- Remarks:
- Doses / Concentrations:
2, 10, 50 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 13
- Control animals:
- yes, concurrent vehicle
- Positive control:
- no data
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: twice a week the first week ; weekly afterwards, including during the pregnancy of females. Additionnally for females, days 0 & 4 of lactation.
FOOD CONSUMPTION AND COMPOUND INTAKE :
- Food consumption determined in four day blocks during the first week and weekly afterwards.
- Compound intake calculated as mean diet as g food/rat/average over the period of calcul.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: All males (13 per dose group)
- Parameters checked in table 1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: All males (13 per dose group)
- Parameters checked in table 1 were examined.
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
The following tissues were prepared for microscopic examination :
Heart, thymus, spleen AND liver, kidney, adrenal gland, testis, epididymis. These were also weighed. - Other examinations:
- See the chapter 7.8.1 for the exams performed concerning reproductive toxicology.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Males : Temporary salivation after each administration was observed in the 10 mg/kg or more groups.
Females : One female died on post-partum day 3 in the 50 mg/kg group.
BODY WEIGHT AND WEIGHT GAIN
Males : Suppression of body weight gain during the early administration period was noted in the 50 mg/kg group.
Females : Slight decreases in body weight gain and food consumption during the early administration period were observed in the 10 mg/kg or moregroups. In addition, body weight gain and food consumption were decreased during pregnancy in the 50 mg/kg group.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Males : Suppression of food consumption during the early administration period was noted in the 50 mg/kg group.
Females : No effects.
HAEMATOLOGY
Males : Elevated platelet and white blood cell counts were apparent after the administration of the compound at the dose level of 50 mg/kg.
Females : No effects.
CLINICAL CHEMISTRY
Males : Increases in total protein and concentrations of albumin, total cholesterol, Ca and inorganic phosphorus and decreases in the A/G ratio an Cl concentration were apparent after the administration of the compound at the dose level of 50 mg/kg.
Females : No effects.
ORGAN WEIGHTS
Males : Increases in the kidney weights in all the treated groups and in the liver weights in the 10 mg/kg or more groups were observed at autopsy.
Females : Liver and kidney weights showed a tendency for increase in the 50 mg/kg group (observed at autopsy on post-partum day 4).
GROSS PATHOLOGY
No effects.
HISTOPATHOLOGY: NON-NEOPLASTIC
Males : Increased eosinophilic bodies and basophilic changes of the renal tubular epithelial cells in the kidneys of males treated with the compound atany dose levels tested were noted, as well as granular casts in the lower nephrons. Centrilobular hypertrophy of hepatocytes was also detected in the 10 mg/kg or more groups.
Females : Centrilobular hypertrophy of hepatocytes was observed in the 10 mg/kg or more groups.
The NOEL for toxicity was suggested by the authors to be less than 2 mg/kg/day in males and 2 mg/kg in females. In the Japan HPV document, as renal pathological changes were observed only in males, accumulation of alpha-2-macroglobulin was suspected as a cause of male specific renal toxicity. Therefore, based on pathological changes in liver of both sexes, NOEL was considered to be 2 mg/kg/day for both sexes, based on liver toxicity.
Effect levels
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- < 2 mg/kg bw/day (actual dose received)
- Sex:
- male
- Basis for effect level:
- other: Histopathology (kidneys)
- Dose descriptor:
- NOEL
- Effect level:
- 2 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- other: Body weight; food consumption; histopathology (liver)
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
The NOEL for toxicity was suggested to be less than 2 mg/kg/day in males and 2 mg/kg in females by the authors.
Considering the fact that only males were observed with renal changes, it is assumed that alpha-2-macroglobulin is involved in the specific toxicity observed. Then, the NOEL for the test item is 2 mg/kg/day for both sexes, based on liver toxicity. - Executive summary:
A study was conducted at Hatano Research Institute, Japan to evaluate the repeated dose toxicity and effects of the test substance 2,2’-Azobis(2-methylpropionitrile) (ABMPN) on the reproductive performance in parental animals and development and growth of F1 pups until day 4 of lactation. The study was conducted according to GLP and to OECD Guidelines for Testing of Chemicals: Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test” (March 22, 1990).
The study design consisted of 13 male and 13 female Sprague-Dawley (Crj:CD) rats per group, dosed at 0 (vehicle control), 2, 10 and 50 mg/kg for 2 weeks before mating and for 2 weeks after mating, followed by additional 2 weeks after completion of mating in males and throughout the gestation period until Day 3 of lactation after parturition in females.
In the males, ABMPN induced transient salivation at 10 mg/kg or greater doses and inhibited weight gain and feed consumption at an early stage of the treatment at 50 mg/kg. Necropsy conducted after repeated administration of 42 doses revealed increases in kidney weight at 2 mg/kg or greater doses and increases in liver weight at 10 mg/kg or greater doses. Findings in histopathological examinations included increases in eosinophilic bodies and basophilic renal tubules and the presence of granular casts at 2 mg/kg or greater doses, as well as centrilobular hypertrophy of hepatocytes at 10 mg/kg or greater doses. Hematological examinations of blood samples taken during necropsy showed increases in platelets and WBC at 50 mg/kg. Blood biochemistry revealed increases in the concentrations of total protein, albumin, total cholesterol, calcium and inorganic phosphorus, as well as decreases in the A/G ratio and Cl at 50 mg/kg.
In the females, ABMPN inhibited weight gain and feed consumption at an early stage of treatment at 10 mg/kg or greater doses. At 50 mg/kg, it also inhibited weight gain and feed consumption during gestation. One animal died 3 days after parturition. Necropsy conducted 4 days after parturition revealed a tendency toward increases in weight of the liver and kidneys. Findings obtained in histopathological examinations suggested centrilobular hypertrophy of hepatocytes at 10 mg/kg or greater doses.
Findings revealed that ABMPN had no effects on the copulation index or fertility index at 50 mg/kg or lower doses. ABMPN did not affect the length of the gestation period or delivery index in maternal animals, either. No abnormal parturition was observed. Abnormal nursing behavior was noted in 3 animals from the 50 mg/kg group.
The findings in offspring showed that ABMPN had no effects on the parturition index, live pup delivery index, overall delivery index, or the sex ratio and body weight on Day 0. In the 50 mg/kg group, the offspring viability index and body weight on Day 4 of lactation showed a tendency to decrease. No offspring from the ABMPN groups showed any morphological anomaly.
It was concluded that under the conditions of the present study, the NOEL for parental toxicity of ABMPN is slightly lower than 2 mg/kg/day in males and 2 mg/kg/day in females and that the NOEL for reproduction/developmental toxicity is 50 mg/kg/day in males and 10 mg/kg/day in females and offspring.
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