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EC number: 617-143-5 | CAS number: 80675-49-6
- 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:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- Version 27 July 1995
- Deviations:
- no
- GLP compliance:
- yes
- Remarks:
- Research Toxicology Center S.p.A., Pomezia, Italy
- Limit test:
- no
Test material
- Reference substance name:
- 2-[(1E)-2-(2-methoxy-5-nitrophenyl)diazen-1-yl]-N-(2-methoxyphenyl)-3-oxobutanamide
- EC Number:
- 617-143-5
- Cas Number:
- 80675-49-6
- Molecular formula:
- C18H18N4O6
- IUPAC Name:
- 2-[(1E)-2-(2-methoxy-5-nitrophenyl)diazen-1-yl]-N-(2-methoxyphenyl)-3-oxobutanamide
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Identifier: CAS 80675-49-6
- Lot/batch No.: L-7015-20
- Yellow powder
- Storage conditions: Ambient temperature, no protection from light necessary
Constituent 1
- Specific details on test material used for the study:
- - Identifier: CAS 80675-49-6
- Lot/batch No.: L-7015-20
- Analytical purity: 95%
- Yellow powder
- Storage conditions: Ambient temperature, no protection from light necessary
Test animals
- Species:
- rat
- Strain:
- other: HsdBrl: wistar Han rats
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Italy s.r.l.
- Age at study initiation: 6 - 7 weeks
- Weight at study initiation: (P) ♂: 183 - 197 g; ♀: 155 - 164 g
- Housing: in a limited access rodent facility
- Pre-mating period: 5 animals per sex per cage
- Mating period: one male to one female
- Post mating: animals were housed individually
- Diet: commercially available laboratory powdered rodent diet (4 RF 21, Mucedola R.r.l., Italy)
- Water: ad libitum
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): 15 - 25
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: 2011-03-24 to 2011-05-21
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): fresh diet were prepared according to the stability of the test substance in the diet.
- Mixing appropriate amounts with: commercially available laboratory powdered rodent diet (4 RF 21, Mucedola R.r.l., Italy)
- Storage temperature of food: room temperature - Details on mating procedure:
- - M/F ratio per cage: monogamous
- Length of cohabitation: until mating
- Proof of pregnancy: vaginal plug or sperm in vaginal smear were referred to as day 0 of pregnancy.
- After successful mating each pregnant female was caged: in individual clear polycarbonate cages with stainless mesh lid and floor
- Any other deviations from standard protocol: - for females from day 14 to day 20 post coitum and from day 0 to day 4 post partum the achieved dosage was calculated at 6 and 4 days interval, respectively and not weekly as indicated in the study protocol - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analysis were performed to confirm that the proposed formulation procedure was acceptable and that the homogeneity and stability of the formulation were satisfactory. Samples of the formulations prepared in week 1 and last week of the study were analysed to check the homogeneity and concentration. Chemical analysis were carried out by the Analytical Chemistry Department at RTC. The software used for this activity was the Empower® Pro build No. 2154.
- Duration of treatment / exposure:
- ♂: 7 days a week for 2 consecutive weeks prior to pairing and thereafter until day of necropsy (total of 30-31 days of treatment).
♀: 7 days a week for 2 consecutive weeks prior to pairing and thereafter during mating, gestation and post partum until day 4 post partum. - Frequency of treatment:
- daily, 7 days a week
- Details on study schedule:
- - Age at mating of the mated animals in the study: 10 - 11 weeks
Doses / concentrationsopen allclose all
- Dose / conc.:
- 1 500 ppm (nominal)
- Dose / conc.:
- 5 000 ppm (nominal)
- Dose / conc.:
- 15 000 ppm (nominal)
- Dose / conc.:
- 123 mg/kg bw/day
- Remarks:
- ♂. mean dose value as calculated from the reported body weight and standard food intake values
- Dose / conc.:
- 420 mg/kg bw/day
- Remarks:
- ♂: mean dose value as calculated from the reported body weight and standard food intake values
- Dose / conc.:
- 1 271 mg/kg bw/day
- Remarks:
- ♂: mean dose value as calculated from the reported body weight and standard food intake values
- Dose / conc.:
- 151 mg/kg bw/day
- Remarks:
- ♀: mean dose value as calculated from the reported body weight and standard food intake values
- Dose / conc.:
- 537 mg/kg bw/day
- Remarks:
- ♀: mean dose value as calculated from the reported body weight and standard food intake values
- Dose / conc.:
- 1 496 mg/kg bw/day
- Remarks:
- ♀: mean dose value as calculated from the reported body weight and standard food intake values
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: dose levels were selected in consultation with the sponsor.
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: on day of allocation to the treatment groups. ♂: additionally on day that treatment commenced, weekly thereafter and just prior to necropsy. ♀: weekly from the first day of treatment to mating, on days 0, 7, 14, and 20 post coitum and on days 1 and 4 post partum.
FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean weekly diet consumption calculated as ppm food/kg body weight/week: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes - Oestrous cyclicity (parental animals):
- The distribution of the oestrus cycle was determined
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain
GROSS EXAMINATION OF DEAD PUPS:
Yes, for size and external abnormalities. Possible cause of death was not determined for pups born or found dead. - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals, after the mating of all females (30 - 31 days of treatment).
- Maternal animals: All surviving animals, females with live pups were killed on day 4 post partum, females with no birth 25 days after positive identification of mating were killed shortly after, one female with litter loss was killed on day1 post partum.
GROSS NECROPSY
- Gross necropsy consisted of external examination of surfaces and orifices and requisite organs with changes were weighed and tissue samples preserved.
HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table 1 were prepared for microscopic examination. - Postmortem examinations (offspring):
- SACRIFICE
- The F1 offspring were sacrificed at 4 days of age.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows: external abnormalities, sex confirmation by gonadal inspection - Statistics:
- For continous variables significance of differences amongst group means were assessed by Dunnett's test or a modified t-test depending on homogeneity of data. Non-continous variables were statistically analyzed by means of Kruskal-Wallis Test and intergroup differences between the control and treated groups assessed by a non-parametric version of Williams test. Statistical analyzes of histopathological findings was carried out by means of the non-parametric Kolmogorov-Smirnov test. The mean values and standard deviations were calculated from actual values in the computer without rounding off.
- Reproductive indices:
- ♂:
Copulatory Index (%) = no. of animals mated x 100/No. of animals paired
Fertility Index (%) = no. of males which induced pregnancy x 100/No. of males paired
♀:
Copulatory Index (%) = no. of animals mated x 100/No. of animals paired
Fertility Index (%) = no. of pregnant females x 100/No. of females paired
♂ and ♀:
Copulatory Interval = Mean number of days between pairing and mating - Offspring viability indices:
- Pre-birth loss (%): (No. of visible implantations - total litter size) x 100/No. of visible implantations
Pup loss at birth (%): (Total litter size - live litter size) x 100/Total litter size
Cumulative pup loss on day 4 post partum (%): (Total litter size at birth - live litter size at day 4) x 100/Total litter size at birth
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Yellow staining of the fur was evident in all treated males and in mid and high dose females during entire treatment period.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A slight statistically significant reduction in body weight was noted in the high dose females on gestation day 20. This change was not considered to be of toxicological relevance since it was related to the presence of one female with total litter loss and the smal size of few litters.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- Minimal degenerative changes were noted in the seminoferous epithelium of the testes of one male of the high dose group. However, regular layering of the different cell populations in the germinal epithelium in each stage leads to consider such effect as spontaneous pathology.
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Description (incidence and severity):
- The distribution of the oestrus cycle and reproductive parameters were comparable between all animals mated.
- Reproductive performance:
- effects observed, non-treatment-related
- Description (incidence and severity):
- One female in the control group, 2 in the low dose group, one in the mid-dose group and one in the high dose group were not pregnant. Unilateral implantation was present in one mid-dose and one high-dose female. One mid-dose female had unilateral total resorption and one high-dose female had total litter loss.
Effect levels (P0)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 15 000 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: NOAEL corresponding to the highest dose tested
- Dose descriptor:
- NOAEL
- Effect level:
- 1 271 mg/kg bw/day
- Based on:
- other: mean dose value as calculated from the reported body weight and standard food intake values
- Sex:
- male
- Basis for effect level:
- other: NOAEL corresponds to the highest achieved dose level
- Dose descriptor:
- NOAEL
- Effect level:
- 1 496 mg/kg bw/day
- Based on:
- other: mean dose value as calculated from the reported body weight and standard food intake values
- Sex:
- female
- Basis for effect level:
- other: NOAEL corresponds to the highest achieved dose level
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Sexual maturation:
- no effects observed
- Gross pathological findings:
- no effects observed
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEC
- Generation:
- F1
- Effect level:
- > 15 000 ppm (nominal)
- Sex:
- male/female
- Basis for effect level:
- mortality
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Any other information on results incl. tables
Table 2: Implantation, pre-birth loss and gestation length - Group mean data
Group | Corpora Lutea | Implantations | Total Litter Size | Pre-birth loss (%) | Gestation length (days) | |
1 | Mean | 13.22 | 13.00 | 11.89 | 8.70 | 22.0 |
Std | 1.56 | 1.58 | 1.83 | 7.40 | 0.71 | |
N | 9 | 9 | 9 | 9 | 9 | |
2 | Mean | 11.50 | 11.00 | 9.38 | 16.95 | 22.0 |
Std | 3.25 | 3.96 | 3.54 | 11.9 | 0.53 | |
N | 8 | 8 | 8 | 8 | 8 | |
3 | Mean | 12.25 | 12.00 | 11.25 | 7.29 | 22.00 |
Std | 3.15 | 3.07 | 3.15 | 6.23 | 0.00 | |
N | 8 | 8 | 8 | 8 | 8 | |
4 | Mean | 12.50 | 11.00 | 9.50 | 14.90 | 22.0 |
Std | 2.83 | 4.00 | 4.31 | 20.31 | 0.53 | |
N | 8 | 8 | 8 | 8 | 8 |
Table 3: Reproductive Parameters of males - Summary data
groups | 1 | 2 | 3 | 4 | |
copulatory index (%) | 100.0 | 100.0 | 100.0 | 100.0 | |
fertiliy index (%) | 90.0 | 80.0 | 90.0 | 90.0 |
Table 4: Reproductive Parameters of females - Summary data
groups | 1 | 2 | 3 | 4 | |
copulatory index (%) | 100.0 | 100.0 | 100.0 | 100.0 | |
fertiliy index (%) | 90.0 | 80.0 | 90.0 | 90.0 |
Applicant's summary and conclusion
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.