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EC number: 201-132-3 | CAS number: 78-67-1
- 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

Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Study period:
- 1997
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
Data source
Reference
- Reference Type:
- secondary source
- Title:
- no data
- Author:
- MHW, Japan
- Year:
- 1 997
- Bibliographic source:
- cited in OECD SIDS Final 08/02
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)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Reference substance 001
- Details on test material:
- - purity: 99.9%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on mating procedure:
- - premating exposure period: 14 days
- Duration of treatment / exposure:
- male: from 14 days before mating to 14 days after mating; males were exposed for 42 days
female: from 14 days before mating to day 3 of lactation - Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 2 mg/kg bw/day (nominal)
- Dose / conc.:
- 10 mg/kg bw/day (nominal)
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 13
- Control animals:
- yes, concurrent vehicle
Examinations
- Parental animals: Observations and examinations:
- BODY WEIGHT: Yes
- Time schedule for examinations: twice a week the first week; weekly afterwards, including during the pregnancy of females. Additionally for females, days 0 and 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 in mean diet as g food/rat/average over the period of calcul. - Sperm parameters (parental animals):
- Parameters examined in all male parental generations: testis weight, epididymis weight
- Litter observations:
- STANDARDISATION OF LITTERS
no
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, live births, postnatal mortality (on day 4), body weight recorded on day 0 and day 4.
GROSS EXAMINATION OF DEAD PUPS
yes, morphological - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals on day 43.
- Maternal animals: All surviving animals on day 4 post partum.
HISTOPATHOLOGY / ORGAN WEIGHTS
The following tissues were prepared for microscopic examination: Heart, thymus, spleen and liver, kidney, adrenal gland, testis, epididymis. These ones were also weighed. - Postmortem examinations (offspring):
- SACRIFICE
- Supposed on day 4. Not accurately indicated.
GROSS NECROPSY
- Gross necropsy consisted of external examinations - Reproductive indices:
- Copulation index, fertility index, gestation index, duration of pregnancy
- Offspring viability indices:
- viability index
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Males: Temporary salivation after each administration was observed in the animals exposed at 10 mg/kg and more.
Females: One female in the 50 mg/kg group died on post-partum day 3. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Males: Suppression of body weight gain and food consumption during the early administration period were noted in the 50 mg/kg group.
Females: Slight decrease in body weight gain and food consumption during the early administration period were observed in the animals exposed at 10 mg/kg and more. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Males: Increased eosinophilic bodies and basophilic changes of the renal tubular epithelial cells in the kidneys of all the animals exposed were noted, as well as granular casts in the lower nephrons. Centrilobular hypertrophy of hepatocytes was also detected in the groups of animals exposed at 10 mg/kg and more.
Females: Centrilobular hypertrophy of hepatocytes was observed in the groups of animals exposed at 10 mg/kg and more.
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- The compound showed no adverse effects on copulation and fertility, duration of pregnancy, gestation index and parturition at any of the dose levels tested. Three dams in the 50 mg/kg group showed abnormal lactation.
Details on results (P0)
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No effect on reproductive toxicity in males
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: At 50 mg/kg bw/d, abnormal lactation in 3 dams
Target system / organ toxicity (P0)
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Mortality / viability:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Gross pathological findings:
- no effects observed
Details on results (F1)
For reproductive and developmental toxicity the NOEL was 10 mg/kg in pups according to the authors.
It was considered that the effects on pups were caused by maternal toxicity since a difficulty in nursing (lactation) was reported. Then the NOAEL for reproduction in offspring was considered to be 50 mg/kg.
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 10 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: decreased viability index and body weight on day 4 at 50 mg/kg/day
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
General parenteral toxicity:
There were no adverse effects of 2,2'-azobis(2- methylpropanitrile) on copulation and fertility, duration of pregnancy, gestation index and parturition at all treated group. Three of 12 dams at 50 mg/kg showed the difficulty of nursling and two of them let all their offsprings die within the first 4 days after birth.
Toxicity to offspring:
This compound showed no adverse effects on viability, sex ratio and body weight gain of pups. However, viability of newborns at birth and body weight of nurslings on postnatal day 4 was lower than the control levels at 50 mg/kg/day. These changes were considered to be caused by maternal toxicity. There were no morphological abnormalities in pups at all treated groups.
Table 1: Summary of development of pups
Dose (mg/kg) |
0 |
2 |
10 |
50 |
Number of pregnant females |
12 |
12 |
11 |
12 |
Number of pregnant females with pup alive |
12 |
12 |
11 |
12 |
Gestation Index |
100 |
100 |
100 |
100 |
Gestation length in days |
22.3 +/-0.5 (12) |
22.1 +/-0.3 (12) |
22.2 +/-0.4 (11) |
22.4 +/-0.5 (12) |
Number of corpora lutea |
18.8 +/-2.5 (12) |
17.8 +/-1.5 (12) |
18.1 +/-2.0 (11) |
16.9 +/-2.0 (12) |
Number of implantation sites |
17.3 +/-25 (12) |
16.8 +/-1.5 (12) |
17.1 +/-2.1 (11) |
15.6 +/-1.4 (12) |
Implantation index |
92.9 +/-10.6 (12) |
95.0 +/-5.7 (12) |
94.7 +/-7.7 (11) |
92.8 +/-9.3 (12) |
Day 0 of lactation |
|
|
|
|
Number of pups born |
15.4 +/-2.5 (12) |
15.8 +/-1.9 (12) |
15.5 +/- 1.8 (11) |
14.8 +/-1.5 (12) |
Delivery index |
88.8 +/-6.2 (12) |
94.0 +/-6.1 (12) |
91.6 +/-10.3 (11) |
94.6 +/-4.4 (12) |
Number of pups alive |
15.0 +/-2.5 (12) |
15.8 +/-1.9 (12) |
15.5 +/-1.8 (11) |
14.8 +/-1.5 (12) |
Birth index |
86.6 +/- 8.3 (12) |
93.5 +/- 5.8 (12) |
91.6 +/-10.3 (11) |
94.6 +/-4.4 (12) |
Live birth index |
97.4 +/-4.9 (12) |
99.4 +/- 1.9 (12) |
100.0 +/-0.0 (11) |
100.0 +/- 0.0 (12) |
Pup weight in grams |
|
|
|
|
Male |
6.2 +/-0.6 (12) |
6.3 +/-0.5 (12) |
6.3 +/-0.4 (11) |
6.1 +/-0.2 (12) |
Female |
5.9 +/-0.5 (12) |
6.0 +/-0.5 (12) |
6.0 +/-0.3 (11) |
5.9 +/-0.2 (12) |
Sex ratio |
50.5 +/-9.9 (12) |
43.9 +/-12.8(12) |
54.4 +/-10.9 (11) |
53.6 +/-11.7 (12) |
Day 4 of lactation |
|
|
|
|
Number of pups alive |
14.6 +/-2.3 (12) |
15.6 +/-1.9 (12) |
15.5 +/-1.8 (11) |
11.6 +/-5.9 (12) |
Viability index |
97.5 +/-4.1 (12) |
99.0 +/-2.4 (12) |
100.0 +/-0.0 (11) |
77.9 +/-38 (12) |
Pup weight in grams |
|
|
|
|
Male |
9.8 +/-1.4 (12) |
9.8 +/-1.1 (12) |
9.8 +/-1.0 (11) |
9.0 +/-1.2 (12) |
Female |
9.5 +/-1.2 (12) |
9.5 +/-1.1 (12) |
9.4 +/-1.0 (11) |
8.5 +/-1.1 (12) |
Gestation Index: Number of pregnant female with pups alive/Number of pregnant females
Implantation Index: Number of implantation sites/Number of corpora lutea *100 (%)
Delivery Index: Number of pups born/Number of implantation sites *100 (%)
Birth Index: Number of pups alive on day 0/ Number of implantation sites *100 (%)
Live Birth Index: Number of pups alive on day 0/ Number of pups born *100 (%)
Sex ratio: Number of male pups alive on day 0/ Number of pups alive on day 0 *100 (%)
Viability index: Number of pups alive on day 4/ Number of pups alive on day 0 *100 (%)
Applicant's summary and conclusion
- Conclusions:
- In conclusion, the NOEL for reproductive and developmental toxicity was 50 mg/kg/day in males and 10 mg/kg/day in females and in pups. According to CLP criteria, the test substance is not classified.
- Executive summary:
The reproductive / developmental toxicity of the test substance was evaluated in male and female rats after oral administration (gavage) at doses of 0, 2, 10 and 50 mg/kg/day until day 43 for males and day 4 of post partum for females.
The test substance had no effects on the copulation index or fertility index at 50 mg/kg or lower doses. The test substance did not affect the length of 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 no effects on the parturition index, live pup delivery index, overall delivery index, or the sex ratio and body weight on day 0 at all dose-levels. 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 test substance treated groups showed any morphological anomaly.
Based on these results, the NOEL for reproductive and developmental toxicity was 50 mg/kg/day in males and 10 mg/kg/day in females and in pups.
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