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EC number: 235-424-7 | CAS number: 12224-98-5
- 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:
- reproductive toxicity, other
- Remarks:
- Teratogenicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Data is from publication
Data source
Reference
- Reference Type:
- publication
- Title:
- THE TERATOGENIC POTENTIAL IN RATS AND RABBITS OF D&C YELLOW NO. 8
- Author:
- C. M. BURNETI, E. I. GOLDENTHAL
- Year:
- 1 986
- Bibliographic source:
- Fd Chem. Toxic, Vol. 24, No. 8, pp. 819 823, 1986
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: as below
- Principles of method if other than guideline:
- Teratogenic Potential study of D & C Yellow No. 8, sodium fluoresce in by Oral Administration in Rats
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- No data available
Test material
- Reference substance name:
- Disodium 2-(3-oxo-6-oxidoxanthen-9-yl)benzoate
- EC Number:
- 208-253-0
- EC Name:
- Disodium 2-(3-oxo-6-oxidoxanthen-9-yl)benzoate
- Cas Number:
- 518-47-8
- Molecular formula:
- C20H12O5.2Na
- IUPAC Name:
- disodium 3-oxo-3H-spiro[2-benzofuran-1,9'-xanthene]-3',6'-diolate
- Details on test material:
- - Name of test material : D & C Yellow No. 8, sodium fluorescein
- Molecular formula : C20H10Na2O5
- Molecular weight : 376.274 g/mol
- Substance type: Organic
- Physical state: No data
Constituent 1
- Specific details on test material used for the study:
- - Name of test material : D & C Yellow No. 8, sodium fluorescein
- Molecular formula : C20H10Na2O5
- Molecular weight : 376.274 g/mol
- Substance type: Organic
- Physical state: No data
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- CD
- Details on species / strain selection:
- No data available
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- - Source:
Female rats: Charles River Breeding Laboratories,Portage, Michigan.
Male rats: Langshaw Farms, Augusta, Michigan
- Age at study initiation:18 weeks
- Weight at study initiation:No data
- Fasting period before study:No data
- Housing:The animals were housed in wire bottomed cages
- Diet (e.g. ad libitum):Purina Certified Rodent Chow No. 5002 ad libitum
- Water (e.g. ad libitum):Water ad libitum
- Acclimation period:4 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C):22.2±-15.5 ˚C
- Humidity (%):50± 15%
- Air changes (per hr):No data
- Photoperiod (hrs dark / hrs light):12 hrs light/dark cycle
IN-LIFE DATES: From: To:
Administration / exposure
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with vehicle at dose levels of 0, 100, 500 or 1500 mg/kg body weight and prepared daily
DIET PREPARATION
- Rate of preparation of diet (frequency):No data
- Mixing appropriate amounts with (Type of food):No data
- Storage temperature of food:No data
VEHICLE
- Justification for use and choice of vehicle (if other than water):No data
- Concentration in vehicle:0, 100, 500 or 1500 mg/kgbw
- Amount of vehicle (if gavage):10 mL/Kg
- Lot/batch no. (if required):No data
- Purity:No data - Details on mating procedure:
- - M/F ratio per cage: 1: 1.
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy Copulatory plug or presence of sperm in vaginal washings was designated as day 0 of gestation - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 14 days (days 6-19 of gestation)
- Frequency of treatment:
- Daily
- Details on study schedule:
- not specified
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Dose / conc.:
- 100 mg/kg bw/day
- Dose / conc.:
- 500 mg/kg bw/day
- Dose / conc.:
- 1 500 mg/kg bw/day
- No. of animals per sex per dose:
- Total: 100 females
0 mg/Kg bw: 25 females
100 mg/Kg bw: 25 females
500 mg/Kg bw: 25 females
1500 mg/Kg bw: 25 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- not specified
- Positive control:
- not specified
Examinations
- Parental animals: Observations and examinations:
- Survival, clinical sign and body weights were examined.
- Oestrous cyclicity (parental animals):
- not specified
- Sperm parameters (parental animals):
- not specified
- Litter observations:
- sex and body weight were examined.
- Postmortem examinations (parental animals):
- Gross pathology were examined.
- Postmortem examinations (offspring):
- Gross external malformations and variations were examined.
- Statistics:
- Differences in the fetal sex distribution and the number of litters with malformations between control and treated groups wcre compared using the Chi-square test criterion with Yates" correction for 2 x 2 contingency lables and, or Fisher's exact probability test as described by Sicgel (1956). The numbers of early and late resorptions, dead foetuses and post-implantation losses were compared between groups by the Mann Whitney U test as described by Siegel (1956) and Well (1970). The mean numbers of viable foetuses, total implantations, corpora lutca and mean t\)etal weights were compared between groups by analysis of variance (oneway classification), Bartlett's test l\~r homogeneity of variances, and the appropriate t test (for equal or unequal variances) as described by Steel & Torric (1960) using Dunnctt's multiple comparison tables (1964).
- Reproductive indices:
- Viable and non-viable foetuses, early and late resorptions, total implantations and corpora lutea were examined.
- Offspring viability indices:
- not specified
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- When treated with 1500 mg/kg bw, Six rats died during the dosing period as compared to control.
Survival was 100% in the controls and the groups receiving 100 and 500 mg/kg of dye. - Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- When treated with 1500 mg/kg bw, slight reductions in body-weight gains as compared to controls, throughout the dosing period
- 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:
- effects observed, treatment-related
- Description (incidence and severity):
- Orange discoloration of the urine was noted in all treated rats during the treatment period.
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- No effect on Viable and non-viable foetuses, early and late resorptions, total implantations and corpora lutea and sex ratio of fetuses were observed as compared to control.
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 500 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- mortality
- body weight and weight gain
- urinalysis
- gross pathology
- reproductive performance
- other: No effect observed
- Remarks on result:
- other: No effects on reproductive performance
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:
- no mortality observed
- Description (incidence and severity):
- No effect on Viable and non-viable fetuses were observed as compared to control.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No effect on Body weight of fetuses were observed as compared to control.
- 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:
- no effects observed
- Description (incidence and severity):
- When treated with 1500 mg/kg bw, A slight increase in the number of litters with unossified sternebrae (sternebrae nos 1-6) and rudimentary 14th rib(s) was observed however, these values fell within the ranges of historical control data.
No biologically meaningful or statistically significant differences in the number of litters and number of fetuses with malformations and number of fetuses or litters with developmental variations were observed in treated rats as compared to control. - 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:
- 1 500 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- body weight and weight gain
- gross pathology
- other: No effect observed
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
Any other information on results incl. tables
Summary of maternal and foetal observations in study of rats given D&C Yellow No. 8 by gavage on days 6-19 of gestation
Parameter
|
Observation |
|
|
||||||||||||||||||||||
0(control) |
100 |
500 |
1500 |
|
|||||||||||||||||||||
No. |
% |
SD |
No. |
% |
SD |
No. |
% |
SD |
No. |
% |
SD |
|
|||||||||||||
Animals on study
|
25 |
- |
- |
25 |
84.0 |
- |
25 |
- |
25 |
25 |
- |
- |
|||||||||||||
Animals that were gravid |
25 |
100.0 |
- |
21 |
0.0 |
- |
21 |
84.0 |
24 |
24 |
96.0 |
- |
|||||||||||||
Animals that died gravid |
0 |
0.0 |
- |
0 |
100 |
- |
0 |
0.0 |
6 |
6 |
24.0 |
- |
|||||||||||||
Animals examined at caesarean section |
25 |
100.0 |
- |
25 |
16.0 |
- |
25 |
100 |
19 |
19 |
76.0 |
- |
|||||||||||||
Non-gravid |
0 |
0.0 |
- |
4 |
84.0 |
- |
4 |
16 |
1 |
1 |
5.3 |
- |
|||||||||||||
Gravid |
25 |
100.0 |
- |
21 |
- |
2.55 |
21 |
84 |
18 |
18 |
94.7 |
- |
|||||||||||||
Dams with viable foetuses |
25 |
100.0 |
- |
21 |
- |
1.06 |
21 |
84 |
18 |
18 |
94.7 |
- |
|||||||||||||
Viable foetuses/dam |
13.3 |
- |
2.92 |
13.1 |
- |
2.16 |
12.6 |
- |
13.9 |
13.9 |
- |
1.30 |
|||||||||||||
Post-implantation loss/dam |
0.9 |
-[ |
1.78 |
0.9 |
- |
1.88 |
0.6 |
- |
2.89 |
0.5 |
- |
0.79 |
|||||||||||||
Total implantations/dam |
14.2 |
- |
2.24 |
14.0 |
- |
- |
13.1 |
- |
2.13 |
14.4 |
- |
1.10 |
|||||||||||||
Corpora lutea/dam |
15.6 |
- |
2.04 |
15.1 |
- |
- |
15.3 |
- |
- |
15.8 |
- |
1.56 |
|||||||||||||
Foetal sex: male Female |
178 154 |
53.6 46.4 |
- |
148 132 |
52.9 47.1 |
- |
130 134 |
49.2 50.8 |
- |
118 133 |
47.0 53.0 |
- |
|||||||||||||
Mean foetal body weight (g) |
3.4 |
- |
0.29 |
3.5 |
- |
0.36 |
3.5 |
- |
0.36 |
3.5 |
- |
0.45 |
Summary of the incidence of malformations and developmental and genetic variations
observed among foetuses from rats given D & C Yellow No. 8 by gavage on days 6-19 of gestation
Observations |
Dose (mg/kg/day)… |
No. of foetuses (no. of litters) |
|||
0 (control) |
100 |
500 |
1500 |
||
No. of litters examined No. of foetuses examined externally No. of foetuses examined viscerally No. of foetuses examined skeletally |
|
25 332 99 |
21 275 81 |
21 264 93 |
18 251 70 |
Malformations observed Skull anomaly Thoracoschisis Gastroschisis Sternoschisis Bent ribs Radius bent Carpal flexure Foetal anasarca Total foetuses (litters) with malformations: |
|
2 (1) 1(1) 2 (1) 1 ( 1 ) 1 (1) 2 (1)
2 (1) 3 (2)
|
6 (3)
6 (3) |
1 (1)
1 (1) |
0 (0) |
Variations observed 27 presacral vertebrae 14th rudimentary rib(s) 14th lull rib(s) 12 full pairs of ribs with bilateral 13th rudimentary ribs |
|
3 (2) 27 (11) 2 (1)
1 (1) |
23 (9) |
1(1) 17 (8) |
2 (1) 49 (14) 2 (1)
|
Skull reduced in ossification Hyoid unossified Vertebrae reduced in ossification Femur reduced in ossification Pubis unossified lschium unossified Femur unossified Metatarsals unossified Sternebrae no. 5 and/or no. 6 unossified Other sternebrae unossified Sternebrae misaligned Major vessel variation Renal papillae not developed and/or distended ureter |
|
4 (3) 7 (5) 2 (1) 1 (1) 2 (1) 2 (1) 1 (1) 1 (1)
33 (9)
8 (6) |
4 (2) 4 (3)
18 (8)
2 (2) |
5 (3) 2 (1)
33 (12) 1 (1) 1 (1) 1 (1)
1 (1) |
4 (2) 9 (3)
29 (11) 9 (4) 1 (1)
2 (2) |
Applicant's summary and conclusion
- Conclusions:
- NOAEL was considered to be 1500 mg/kg/day for P and F1 generation when CD Sprague-Dawley female rats treated with D & C Yellow No. 8, sodium fluorescein orally by gavage for 14 days.
- Executive summary:
In a Teratogenic Potential Test, CD Sprague-Dawley female rats treated with D & C Yellow No. 8, sodium fluorescein in the concentration of 0, 100, 500 or 1500 mg/kg bw orally by gavage in water for 14 days (days 6-19 of gestation). Six rats died during the dosing period at 1500 mg/kg bw as compared to control. Survival was 100% in the controls and the groups receiving 100 and 500 mg/kg of dye. Slight reductions in body-weight gains at 1500 mg/kg bw and Orange discoloration of the urine was noted in all treated rats during the treatment period. No effect on reproductive parameters such as Viable and non-viable fetuses, early and late resorptions, total implantations and corpora lutea and sex ratio of fetuses were observed in treated female rats as compared to control. Green discoloration of the amniotic fluid was observed in 1, 10 and 16 rats at 100, 500 and 1500 mg/kg/day groups, respectively, and the small intestines were green in colour in many rats at 500 mg/Kg group. In addition, No effect on Body weight of fetuses were observed as compared to control. A slight increase in the number of litters with unossified sternebrae (sternebrae nos 1-6) and rudimentary 14th rib(s) was observed at 1500 mg/kg bw however, these values fell within the ranges of historical control data. No biologically meaningful or statistically significant differences in the number of litters and number of fetuses with malformations and number of fetuses or litters with developmental variations were observed in treated rats as compared to control. Therefore, NOAEL was considered to be 1500 mg/kg/day for P and F1 generation when CD Sprague-Dawley female rats treated with D & C Yellow No. 8, sodium fluorescein orally by gavage for 14 days.
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