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EC number: - | CAS number: -
- 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
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2011
- 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:
- 2011
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- 1995
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- bis[2-hydroxy-N,N-bis(2-hydroxyethyl)ethanaminium] 7-{[4-(4-{[2-(cyanoamino)-4-hydroxy-6-oxo-1,6-dihydropyrimidin-5-yl]diazenyl}benzamido)-3-methoxyphenyl]diazenyl}naphthalene-1,3-disulfonate
- Cas Number:
- 115811-45-5
- Molecular formula:
- C29H19N9O10S2.2C6H16NO3
- IUPAC Name:
- bis[2-hydroxy-N,N-bis(2-hydroxyethyl)ethanaminium] 7-{[4-(4-{[2-(cyanoamino)-4-hydroxy-6-oxo-1,6-dihydropyrimidin-5-yl]diazenyl}benzamido)-3-methoxyphenyl]diazenyl}naphthalene-1,3-disulfonate
- Test material form:
- solid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Han Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories, B.V., Kreuzelweg 53, 5961 NM Horst / Netherlands
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Age at study initiation: (P) 11 wks; (F1) x wks
- Weight at study initiation: (P) Males: 289-338 g; Females: 182-211 g; (F1) Males: x-x g; Females: x-x g
- Fasting period before study: not specified
- Housing: Individually in Makrolon type-3 cages. During the prepairing period, cages with males were interspersed amongst those holding females to promote the development of regular estrus cycles
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12 fluorescent light
IN-LIFE DATES: From: 09/10/2010 To: 11/11/2010
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- First Test Item Administration: Males and Females: Day 1 of pre-pairing
- Details on mating procedure:
- - M/F ratio per cage:
- Length of cohabitation:
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: [no / yes (explain)]
- After successful mating each pregnant female was caged (how):
- Any other deviations from standard protocol: - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- Males were treated over a 14-day pre-pairing period and during the pairing period up to
one day before necropsy (ca. 4 weeks). Females were treated throughout the pre-pairing, pairing, gestation and lactation period up to the day 3 post partum (7 weeks). - Frequency of treatment:
- Once daily: A standard dose volume of 10 mL/kg body weight with a daily adjustment to the actual body weight was used.
- Details on study schedule:
- - F1 parental animals not mated until [...] weeks after selected from the F1 litters.
- Selection of parents from F1 generation when pups were [...] days of age.
- Age at mating of the mated animals in the study: [...] weeks
Doses / concentrationsopen allclose all
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- control group (vehicle, Milli Q-Water)
- No. of animals per sex per dose:
- Number of animals: 40 males: 10 per group; 40 females: 10 per group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The dose levels were selected based on a previous Subacute 28-Day Oral Toxicity (Gavage) Study with Yellow PE 3260/SF in Han Wistar rats, RCC Project Number 632182, using dose levels of 0, 50, 200 and 1000 mg/kg/day, where no adverse effects were detected up to and including the dose level of 1000 mg/kg bw/day.
- Rationale for animal assignment (if not random): Computer-generated random algorithm. In addition body weights (recorded on the day of allocation) were taken into consideration in order to ensure similar mean body weights in all groups.
Examinations
- Parental animals: Observations and examinations:
- VIABILITY/MORTALITY: Yes, twice daily.
CLINICAL OBSERVATIONS: Yes
Daily cage-side clinical observations (once daily, during acclimatization and up to day of necropsy). Additionally females were observed for signs of difficult or prolonged parturition, and behavioral abnormalities in nesting and nursing.
BODY WEIGHT: Yes
- Time schedule for examinations: daily from treatment start to day of necropsy.
FOOD CONSUMPTION AND COMPOUND INTAKE:
Males: Weekly during pre-pairing and after pairing periods.
Females: Pre-pairing period days 1 - 8 and 8 - 14, gestation period days 0 - 7, 7 - 14 and 14 - 21 post coitum and lactation period days 1 - 4 post partum.
- Litter observations:
- The litters were examined for litter size, live births, still births and any gross anomalies. The sex ratio of the pups was recorded. Pups were weighed individually (without identification) on day 1 and 4 post partum.
- Postmortem examinations (parental animals):
- SACRIFICE
Males were sacrificed after they had been treated for at least 28 days.
If birth did not occur on the expected date (day 21 post coitum), the dam was sacrificed on day 25 post coitum.
GROSS NECROPSY
All parent animals and pups were examined macroscopically for any structural changes. For the parent animals, special attention was directed at the organs of the reproductive system. The number of implantation sites and corpora lutea were recorded for all dams with litters. The uteri of non-pregnant females were placed in a solution of ammonium sulfide to visualize possible hemorrhagic areas of implantation sites
HISTOPATHOLOGY / ORGAN WEIGHTS
Slides of all organs and tissues collected at terminal sacrifice from the animals of the control and high-dose groups were examined by the study pathologist. The same applied to all occurring gross lesions.
Special emphasis was made on the stages of spermatogenesis and histopathology of interstitial cell structure.
Histological examination of ovaries was carried out on any females that did not give birth. In addition, microscopic examination of the reproductive organs of all infertile males was made.
At the scheduled sacrifice, the testes and epididymides of all parental males were weighed separately. - Postmortem examinations (offspring):
- SACRIFICE
Dams and pups were sacrificed on day 4 post partum.
GROSS NECROPSY
Dead pups, were examined macroscopically. All parent animals and pups were examined macroscopically for any structural changes
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- All animals survived until the scheduled necropsy.
No adverse effects were noted in males or females at any dose levels.
Treatment with the test item caused orange discoloration of feces in all animals at the dose levels
of 100, 300 and 1000 mg/kg bw/day. This effect was a result of staining ability of the test item
and considered not to be adverse to the animals. - Mortality:
- no mortality observed
- Description (incidence):
- All animals survived until the scheduled necropsy.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No test item-related effects on body weights or body weight gain of males or females were observed at any dose level.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No test item-related effects on food consumption of males or females were observed at any dose
level. - Organ weight findings including organ / body weight ratios:
- no effects observed
Reproductive function / performance (P0)
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- No test item-related effects on the relevant reproductive data (mating performance, fertility,
corpora lutea count, implantation rate and post-implantation loss, duration of gestation, litter size
at first litter check or postnatal loss) were observed at any dose level.
Details on results (P0)
Gross pathology findings were considered to be within the range of normal background lesions. Only findings common in rats of this strain and age have been noted during gross pathology. All of them were within the range of historical control and are reflecting the usual individual variability. No significant findings for organ weights.
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: NOAEL for general toxicity (highest dose level used in the study)
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: NOEL for reproduction/developmental toxicity (the highest dose level used in the study)
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No findings were noted in pups at first litter check or during the first 4 days post partum.
Pups sex ratio was not affected by the treatment with the test item at any dose level. - Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No effects were observed on pup body weight and body weight gain during the first four days
post partum at any dose level. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No findings were noted during macroscopic examination of pups at any dose level.
Details on results (F1)
Effect levels (F1)
open allclose all
- Dose descriptor:
- NOEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: NOEL for reproduction / developmental toxicity
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: NOAEL for general toxicity
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
The only effect seen under the conditions of this test was the discoloration of feces occurring in all animals which received the test item. The NOAEL (No Observed Adverse Effect Level) for general toxicity was established at 1000 mg/kg/bw/day (the highest dose level used in the study).
The NOEL (No Observed Effect Level) for reproduction/developmental toxicity was established at 1000 mg/kg bw/day (the highest dose level used in the study).
Applicant's summary and conclusion
- Conclusions:
- Based on the discoloration of feces occurring in all animals which received the test item, the
NOAEL (No Observed Adverse Effect Level) for general toxicity was established at 1000 mg/kg
bw/day (the highest dose level used in the study).
The NOEL (No Observed Effect Level) for reproduction/developmental toxicity was established
at 1000 mg/kg bw/day (the highest dose level used in the study). - Executive summary:
This study is a valid investigation of the toxicological effects resulting from repeated oral-gavage administration of the test item Yellow PE 3260/SF to rats. Yellow PE 3260/SF was administered in Milli-Q-Water as vehicle at dosages of 100, 300, and 1000 mg/kg body weight/day, and controls received the vehicle only. Yellow PE 3260/SF was administered to male rats for at least 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 pups reached day 4 post partum.
All animals survived the scheduled study period.
With the exception for discoloration of feces, no other test item-related findings were noted in males or females at any dose level. The orange discoloration of feces was observed in all animals treated with the test item. This finding was a result of staining ability of the test item and was considered not to be adverse.
No indices of a general toxicity were observed during the entire study at any dose level. Food consumption, body weights and body weight gain were not affected by the treatment at any dose level. No macroscopical or histopathological findings, which were related to the treatment, were found in males or females in any group as well no changes of organ weights were observed.
The reproduction and developmental parameters investigated within this study did not give any indication of any test item-related effect.
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