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EC number: 282-617-7 | CAS number: 84281-74-3
- 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:
- fertility, other
- Remarks:
- Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data from secondary source
Data source
Reference
- Reference Type:
- secondary source
- Title:
- SIDS Initial Assessment Profile
- Author:
- OECD SIDS
- Year:
- 2 003
- Bibliographic source:
- SIAM 16, 2003
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)
- Principles of method if other than guideline:
- Reproductive toxicity study of test material in Rats
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- Not specified
Test material
- Reference substance name:
- 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[3-oxo-N-phenylbutyramide]
- EC Number:
- 228-787-8
- EC Name:
- 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[3-oxo-N-phenylbutyramide]
- Cas Number:
- 6358-85-6
- Molecular formula:
- C32H26Cl2N6O4
- IUPAC Name:
- Pigment Yellow 12
- Details on test material:
- - Name of test material: Diarylanilide Yellow
- Molecular formula: C32H26Cl2N6O4
- Molecular weight: 629.5014 g/mol
- Substance type: Organic
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- Not specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Age: 14 weeks
- Weight at study initiation: 503 g (males); 280 g (females)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- polyethylene glycol
- Details on exposure:
- Details on oral exposure
PREPARATION OF DOSING SOLUTIONS: Test material dissolved in PEG
DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:
VEHICLE
- Justification for use and choice of vehicle (if other than water): Test material dissolved in PEG
- Concentration in vehicle: 0, 50, 200 and 1000 mg/kg bw
- Amount of vehicle (if gavage):10ml/kg
- Lot/batch no. (if required):
- Purity: - Details on mating procedure:
- - M/F ratio per cage:1:1
- Length of cohabitation:
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy:presence of spermatozoa in a vaginal smear
- 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
- Details on analytical verification of doses or concentrations:
- - Method: spectrophotometrically (accuracy, homogeneity and stability)
- Sampling time: week 1 and week 6 - Duration of treatment / exposure:
- males 4 weeks; females 6-7 weeks; animals were treated 2 weeks before mating and during mating (1:1) treatment was continued; after successful mating (presence of spermatozoa in a vaginal smear) males were treated until a total treatment time of 28 days; females were dosed during pregnancy, were allowed to litter and dosed during the lactation period until they were scheduled for necropsy (4-6 days of lactation)
- Frequency of treatment:
- Daily
- Details on study schedule:
- Not specified
Doses / concentrations
- Remarks:
- 0, 50, 200 and 1000 mg/kg bw
- No. of animals per sex per dose:
- Total: 80
0 mg/kg: 10 male and 10 female
50 mg/kg: 10 male and 10 female
200 mg/kg: 10 male and 10 female
1000 mg/kg: 10 male and 10 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Not specified
- Positive control:
- Not specified
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
- Cage side observations checked in table [No.?] were included.
DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:
BODY WEIGHT: Yes
- Time schedule for examinations:
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data - Oestrous cyclicity (parental animals):
- Not specified
- Sperm parameters (parental animals):
- Parameters examined in [all/P/F1/F2] male parental generations:
testis weight, epididymis weight, - Litter observations:
- Examination of fetuses: as required by OECD 422
- Postmortem examinations (parental animals):
- - Macroscopy: accessory sex organs, epididymides, ovaries, testes and all macroscopic lesions for all animals; according to OECD 422 for 5 animals/sex/group
- Microscopy: not performed - Postmortem examinations (offspring):
- SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at [#?] days of age.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows:
GROSS NECROPSY: yes
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]
HISTOPATHOLOGY / ORGAN WEIGTHS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively. - Statistics:
- Dunnett’s test, Steel test, Fisher’s exact test
- Reproductive indices:
- Not specified
- Offspring viability indices:
- Not specified
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Clinical signs like faeces discolouration was observed in all treated females and male ; incidental animals of all dose groups showed lethargy, hunched posture, laboured respiration, salivation, chromodacryorrhoea, alopecia, scabs and piloerection. Diarrhea and erythema of the anus are attributed to the use of PEG as vehicle.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- Male : : 1/10 at untreated, 50 and 200 mg/kg bw
No mortality in females was observed - Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Male : RBC increased at 50 mg/kg
Female : RBC, Hb/haematocrit increased at 50 mg/kg - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- male:decreased ALAT/ASAT and increased at 200 mg/kg
Female :ALAT/ASAT increase at 1000 mg/kg; phosphate decreased and glucose increased at 200 mg/kg; creatinine decreased at 50 mg/kg
* The increased liver enzymes in high dosed females can be attributed to a single female. Excluding this female leads to mean group values for ASAT and ALAT that are comparable with control values
Effects on blood parameters showed no relationship with the dose and were observed in one of the sexes only. Therefore they were considered to be not toxicological relevant - Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- No effects on weight and no gross findings in the reproductive organs.). No additional findings on the testes were present in any of these animals. The effect on the preputial gland is a common finding in young male rats. No relationship to treatment is suspected.
- Successful mating: no treatment related effects
- % mated: 100%
- Number pregnant per dose level: 9/10 for all dose levels
- Number aborting: none
- Number of implantations: no treatment related effects
- Duration of gestation: 21-22 days
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- food consumption and compound intake
- haematology
- clinical biochemistry
- organ weights and organ / body weight ratios
- gross pathology
- histopathology: non-neoplastic
- reproductive performance
- Remarks on result:
- other: overall no toxic effetcs was observed
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- mortality observed, non-treatment-related
- Description (incidence and severity):
- Viability: Number of litters: 9 at all doses
- Number of litters: 9 at all doses
- Number of dead pups/no litters: at 0, 50, 200 and 1000 mg/kg bw 3/2, 3/2, 1/1 and 0/0, respectively
- Mean live pups/litter: 0, 50, 200 and 1000 mg/kg bw 13, 12, 15 and 14, respectively
- Postnatal loss/no litters: 0, 50, 200 and 1000 mg/kg bw 5/2, 17/4, 9/3 and 6/5, respectively
*. At 50 mg/kg bw 13 pups were lost in one litter - Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- - Macroscopy pups: at 200 mg/kg one pup with malformations was found (a.o. open back/skull); yellow skin in 2 of 10 litters at 1000 mg/kg.The discolourations observed in parents and pups are considered to be related to the staining effect of test substance. From their location it can be concluded that the test substance did not become available systemically, which is in line with other publications on Diarylide Yellow Pigments
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not specified
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- viability
- mortality
- body weight and weight gain
- gross pathology
- Remarks on result:
- other: overall no effects on developmental parameters
Target system / organ toxicity (F1)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Applicant's summary and conclusion
- Conclusions:
- NOAEL was considered to be 1000 mg/kg bw for P and F1 generation when wistar rats were treated with test material orally by gavage according to OECD 422.
- Executive summary:
In a reproductive toxicity study, male andfemale wistar rats were treated with test material in the concentration of 0, 50, 200 and 1000 mg/kg bw orally by gavage formales 4 weeks; females 6-7 weeks; animals were treated 2 weeks before mating and during mating (1:1) treatment was continued; after successful mating (presence of spermatozoa in a vaginal smear) males were treated until a total treatment time of 28 days; females were dosed during pregnancy, were allowed to litter and dosed during the lactation period until they were scheduled for necropsy (4-6 days of lactation). The test material dissolved in PEG and analyzed by spectrophotometrically (accuracy, homogeneity and stability).10 animals/sex /dose group were used. All the animals were observed for Clinical signs, Body weight gain, Food consumption and Examination of uterine content and fetuses were carried out. Macroscopic examination of accessory sex organs, epididymides, ovaries, testes and all macroscopic lesions for all animals; according to OECD 422 for 5 animals/sex/group were done were as Microscopy not performed.
No mortality in females was observed while in male 1/10 at untreated, 50 and 200 mg/kg bwWere observed. Clinical signs like faeces discolouration was observed in all treated females and male ; incidental animals of all dose groups showed lethargy, hunched posture, laboured respiration, salivation, chromodacryorrhoea, alopecia, scabs and piloerection. Diarrhea and erythema of the anus are attributed to the use of PEG as vehicle. No treatment related effects onBody weight, food consumption, organweights andhistopathology. Gross pathology in female showed 1/10 greenish contents of the caecum at 1000 mg/kg
In male hematological examination showed RBC increased at 50 mg/kg while decreased ALAT/ASAT and increased at 200 mg/kg.In female hematological examination showed RBC, Hb/hematocrit increased at 50 mg/kg while ALAT/ASAT increase at 1000 mg/kg; phosphate decreased and glucose increased at 200 mg/kg; creatinine decreased at 50 mg/kg. Effects on blood parameters showed no relationship with the dose and were observed in one of the sexes only. Therefore they were considered to be not toxicological relevant,
The increased liver enzymes in high dosed females can be attributed to a single female. Excluding this female leads to mean group values for ASAT and ALAT that are comparable with control values. The inflammation of the preputial glands seen in 4 of 5 high dosed males was minimal (grade 1-2). No additional findings on the testes were present in any of these animals. The effect on the preputial gland is a common finding in young male rats. No relationship to treatment is suspected
No effects on weight and no gross findings in the reproductive organs. Successful mating as no treatment related effects was observed. Number pregnant per dose level: 9/10 for all dose levels. No abortion was observed. No treatment related effects on Number of implantations and duration of gestation. No effects onViability,Number of dead pups/no litters and Mean live pups/litter was observed. Body weight/sex pups were unchanged.
In macroscopic examination of pups at 200 mg/kg one pup with malformations was found (a.o. open back/skull); yellow skin in 2 of 10 litters at 1000 mg/kg was observed. The discolourations observed in parents and pups are considered to be related to the staining effect of test substance. From their location it can be concluded that the test substance did not become available systemically, which is in line with other publications on Diarylide Yellow Pigments. HenceNOAEL was considered to be 1000 mg/kg bw for P and F1 generation whenwistar rats were treated with test material orally by gavage according to OECD guideline 422.
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