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EC number: 228-787-8 | CAS number: 6358-85-6
- 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
Carcinogenicity
Administrative data
Description of key information
Carcinogenicity of Pigment Yellow 12, the structural analogues, have intensively been investigated. Reliable (RL2) carcinogenicity studies in rats and mice are available for Pigment Yellow 12 and strucrual analogue pigment yellow 83, which all gave negative results. Pigment Yellow 12 has been investigated in two independent laboratories which both studied the effects after chronic exposure of rats and mice. The studies performed at the “Laboratorium für Pharmakologie und Toxikologie” used NMRI mice and Sprague Dawley rats which received up to 9000 ppm Pigment Yellow 12 in diet. Fischer 344 rats and B6C3F1 mice received up to 50000 ppm Pigment Yellow 12 in diet in the studies performed at the National Cancer Institute.
The „Laboratorium für Pharmakologie und Toxikologie“ also performed carcinogenicity tests with structural analogue Pigment Yellow 83 using NMRI mice and Sprague Dawley rats. The animals received up to 9000 ppm pure test item. In two parallel experiments the animals received up to 9000 ppm Pigment Yellow 83 which was intentionally contaminated with 20 ppm 3,3‘-dichlorobenzidine. No carcinogenic effects were observed in any of these tests.
Investigations on genotoxicity of Diarylide Yellow Pigments in vitro and in vivo gave negative results (see section 5.7). Toxicokinetic studies with Diarylide Yellow Pigments indicated that these substances can be considered likely not to be bioavailable. Therefore, it is concluded that Pigment Yellow 12 is not carcinogenic and have not to be classified as carcinogenic.
Please refer also to the read across justification, IUCLID Chapter 13.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reason / purpose for cross-reference:
- read-across source
- Species:
- mouse
- Route of administration:
- oral: feed
- Duration of treatment / exposure:
- 104 weeks
- Remarks:
- Doses / Concentrations:
1000, 3000, 9000 ppm
Basis:
nominal in diet - Statistics:
- - variance analysis according to Peto
- Student's t-test - 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
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Relevance of carcinogenic effects / potential:
- The study design is in accordance with existing guidelines. Therefore, the results are considered relevant for the evaluation of the carcinogenic potential of the test item.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 9 000 ppm (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: no increased tumour incidence in treated animals in comparison to controls, 9000 ppm in diet correspond to 1957.1 mg/kg bw/da and 2030.6 mg/kg bw/day in male and female mice, respectively (calculated in the study report on basis of food consumption)
- Key result
- Critical effects observed:
- no
- Conclusions:
- The toxicity potential of registration substance is assessed using analogue approach.
Chronic feeding of NMRI mice with up to 9000 ppm test item in diet (corresponding to 1957 and 2030 mg/kg bw/day in male and female mice, respectively) did not result in an increased tumour incidence in comparison to the control animals, indicating that the test item is not carcinogenic. - Executive summary:
The toxicity potential of registration substance is assessed using analogue approach.
NMRI mice (50 per sex per dose) were exposed to 1000, 3000, 9000 ppm test item in feed (corresponding to 214, 649, 1957 mg/kg bw/da and 219, 681, 2030 mg/kg bw/day in male and female mice, respectively) for 104 weeks. The test item did not induce a treatment related increase in toxicity or tumour incidences. The results of this study do not provide evidence for carcinogenicity of the test item in NMRI mice.
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From JAN 1974 to APR 1976
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 451 (Carcinogenicity Studies)
- Deviations:
- not specified
- GLP compliance:
- no
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: S. IVANOVAS GmbH & Co, Med. Versuchstierzucht KG (Kissleg, Germany)
- Age at study initiation: 26 (males) -27 (females) days
- Weight at study initiation: 18.1 - 20.1 g
- Housing: individually in Macrolon cages (Type I)
- Diet: Altromin 1321 (Altromin, Lage), ad libitum
- Water: tap water, ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 +/- 0.5
- Humidity (%): 60 +/- 3
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 104 weeks
- Frequency of treatment:
- daily
- Post exposure period:
- none
- Remarks:
- Doses / Concentrations:
1000, 3000, 9000 ppm
Basis:
nominal in diet - No. of animals per sex per dose:
- 50
- Control animals:
- yes, plain diet
- Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice per day
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: daily
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: once, immediately before sacrifice
- Dose groups that were examined: all animals
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
OTHER:
at the end of the exposure period the following investigations were performed:
- audiometry (simple sound test)
- inspection of denture
- organ weights from 7-8 organs (heart, liver, lungs, spleen, kidney, thymus, brain, testis) - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (animals of the control and highest dose group; paraffin sections, Haematoxylin-Eosin staining):
heart, lung, liver (additionally: frozen sections with Sudan stainings), kidney, spleen, adrenal, thymus, pituitary, brain, gonads, thyroid, prostate, uterus, seminal vesicle, mammary gland, stomach, duodenum, colon, salivary gland, lymph nodes, eye and optic nerve, urinary bladder, bone marrow, neoplastic lesions, bones
- histopathological investigations of animals of the lower dose groups were performed, if they died or were sacrificed in the meantime and revealed macroscopic findings - Statistics:
- - variance analysis according to Peto
- Student's t-test - 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
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Relevance of carcinogenic effects / potential:
- The study design is in accordance with existing guidelines. Therefore, the results are considered relevant for the evaluation of the carcinogenic potential of the test item.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 9 000 ppm (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: no increased tumour incidence in treated animals in comparison to controls, 9000 ppm in diet correspond to 1957.1 mg/kg bw/da and 2030.6 mg/kg bw/day in male and female mice, respectively (calculated in the study report on basis of food consumption)
- Key result
- Critical effects observed:
- no
- Conclusions:
- Chronic feeding of NMRI mice with up to 9000 ppm test item in diet (corresponding to 1957 and 2030 mg/kg bw/day in male and female mice, respectively) did not result in an increased tumour incidence in comparison to the control animals, indicating that the test item is not carcinogenic.
- Executive summary:
NMRI mice (50 per sex per dose) were exposed to 1000, 3000, 9000 ppm test item in feed (corresponding to 214, 649, 1957 mg/kg bw/da and 219, 681, 2030 mg/kg bw/day in male and female mice, respectively) for 104 weeks. The test item did not induce a treatment related increase in toxicity or tumour incidences. The results of this study do not provide evidence for carcinogenicity of the test item in NMRI mice.
Referenceopen allclose all
- no substance induced macroscopic or histological changes
- no substance related effects on the tumour incidence (overall tumour rate: 42%, 45%, 40%, 46% in the control, 1000 ppm, 3000 ppm and 9000 ppm dose group, respectively; males: 30%, 36%, 24%, 40%, females: 54%, 54%, 56%, 52% in the control, 1000 ppm, 3000 ppm and 9000 ppm dose group, respectively) - 1000, 3000, 9000 ppm test item in diet correspond to 214, 649, 1957 mg/kg bw/day in male and 219, 681, 2031 mg/kg bw/day in female mice, respectively
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 957 mg/kg bw/day
- Study duration:
- chronic
- Species:
- mouse
- Quality of whole database:
- reliable
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Mode of Action Analysis / Human Relevance Framework
There is no evidence for species specific effects of the substance. Therefore, the results of the in vitro/in vivo data are regarded as relevant for humans.
Justification for classification or non-classification
Due to the negative findings in several reliable studies on carcinogenicity of Pigment Yellow 12 and its strucutral analogue, Pigment Yellow 83, in rats and mice and in the absence of any mutagenic activity of the substances of this category Diarylide Yellow Pigments of this category have not to be classified as carcinogenic according to Regulation (EC) No 1272/2008.
Additional information
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.
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