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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same 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:
- other: OECD 421
- Version / remarks:
- 1995-07-27
- 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
Test animals
- Species:
- rat
- Strain:
- other: HsdBrl: wistar Han rats
- 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, after 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
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 item in the diet.
- Mixing appropriate amounts with (Type of food): commercially available laboratory powdered rodent diet (4 RF 21, Mucedola R.r.l., Italy)
- Storage temperature of food: room temperature - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analysis was performed to confirm that the proposed formulation procedure is acceptable and that the homogeneity and stability of the formulation are 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 was carried out by the Analytical Chemistry Department at RTC. The software used for this activity was the Empower® Pro build No. 2154.
- 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 was 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. - 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
- Duration of test:
- ♀: 54 days, ♂: 30 - 31 days
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 (nominal)
- Remarks:
- ♂: mean dose value as calculated from the reported body weight and standard food intake values.
- Dose / conc.:
- 420 mg/kg bw/day (nominal)
- Remarks:
- ♂: mean dose value as calculated from the reported body weight and standard food intake values.
- Dose / conc.:
- 1 271 mg/kg bw/day (nominal)
- Remarks:
- ♂: mean dose value as calculated from the reported body weight and standard food intake values.
- Dose / conc.:
- 151 mg/kg bw/day (nominal)
- Remarks:
- ♀: mean dose value as calculated from the reported body weight and standard food intake values.
- Dose / conc.:
- 537 mg/kg bw/day (nominal)
- Remarks:
- ♀: mean dose value as calculated from the reported body weight and standard food intake values.
- Dose / conc.:
- 1 496 mg/kg bw/day (nominal)
- 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
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: on the day of allocation to treatment groups. Males additionally on day that treatment commenced, weekly thereafter and just prior to necropsy. Females: 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
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice: males after mating, females & pubs 4 days post partum
- Organs examined: see Table 1 - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes - Fetal examinations:
- - External examinations: Yes, all per litter
- sex ratio, mortality, weights - 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.
- 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
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
Maternal developmental toxicity
- Details on maternal toxic effects:
- Details on maternal toxic effects:
Effects seen were not treatment related. 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. The number of dams with live pups on day4 post partum was 9 in the control group and 8 in the treated groups, respectively. The incidence of pregnancy outcome is comparable with the historical control data (of segment II studies).
Effect levels (maternal animals)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 15 000 ppm (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- 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
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Details on embryotoxic / teratogenic effects:
No treatment related effects were seen (for results see tables in "Any other information on results incl. tables).
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- > 15 000 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reduction in number of live offspring
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental 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: Litter data at birth, on day 1 and on day 4 post partum - Group mean data
at birth | on day1 post partum | on day4 post partum | |||||||||
Group |
Total litter size | Live litter size | Pup loss [%] | Litter weight (g) | Mean pup weight (g) | Live litter size | Cumulative loss (%) | Litter weight (%) | Mean pup weight (g) | ||
1 | Mean | 11.89 | 11.89 | 0.00 | 75.71 | 6.36 | 10.33 | 14.09 | 90.11 | 8 .29 | |
Std | 1.83 | 1.83 | 0.00 | 14.45 | 0.68 | 3.24 | 22.38 | 38.04 | 1.95 | ||
N | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | ||
2 | Mean | 9.38 | 9.13 | 2.39 | 60.65 | 6.88 | 8.63 | 7.44 | 83.03 | 9.84 | |
Std | 3.54 | 3.48 | 4.43 | 21.17 | 0.88 | 3.46 | 11.34 | 32.64 | 1.52 | ||
N | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | ||
3 | Mean | 11.25 | 11 .25 | 0.00 | 72.74 | 6.7 | 10.38 | 6.84 | 97.04 | 9.54 | |
Std | 3.15 | 3.15 | 0.00 | 18.31 | 0.68 | 2.92 | 10.54 | 28.41 | 1.63 | ||
N | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | ||
4 | Mean | 9.5 | 9.5 | 0.00 | 63.95 | 6.96 | 8.25 | 9.61 | 70.99 | 9.00 | |
Std | 4.31 | 4.31 | 0.00 | 32.63 | 2.15 | 3.24 | 12.57 | 22.22 | 1.5 | ||
N | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
Table 4: Sex ratio of pups - Group mean data
at birth | On day4 post partum | ||||||||
Group | M | F | Total | % males | M | F | Total | % males | |
1 | Mean | 6.67 | 5.22 | 11.89 | 57.4 | 5.89 | 4.44 | 10.33 | 58 .79 |
Std | 1.00 | 2.11 | 1.83 | 12.66 | 1.90 | 2.30 | 3.24 | 13.14 | |
N | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | |
2 | Mean | 4.63 | 4.50 | 9.13 | 52.08 | 4.50 | 4.13 | 8.63 | 53.81 |
Std | 1.60 | 2.51 | 3.48 | 10.93 | 1.60 | 2.42 | 3.46 | 11.53 | |
N | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | |
3 | Mean | 5.63 | 5.63 | 11.25 | 51.30 | 5.13 | 5.25 | 10.38 | 50.93 |
Std | 2.72 | 2.72 | 3.15 | 21.20 | 2.47 | 2.60 | 2.92 | 20.61 | |
N | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | |
4 | Mean | 4.50 | 5.00 | 9.50 | 46.05 | 4.00 | 4.25 | 8.25 | 46.15 |
Std | 2.78 | 2.56 | 4.31 | 14.97 | 2.51 | 1.67 | 3.24 | 16.06 | |
N | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
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.