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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 224-618-7 | CAS number: 4430-18-6
- 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
- Study period:
- From 13 August 1999 to 24 September 1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 000
- Report date:
- 2000
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- Adopted 12 May 1981
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- Sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate
- EC Number:
- 224-618-7
- EC Name:
- Sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate
- Cas Number:
- 4430-18-6
- Molecular formula:
- C21H15NO6S.Na
- IUPAC Name:
- sodium 2-[(4-hydroxy-9,10-dioxo-9,10-dihydroanthracen-1-yl)amino]-5-methylbenzenesulfonate
- Test material form:
- solid: particulate/powder
- Remarks:
- Dark Red Violet
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Batch No. 0609RA Lot no. AK0709
- Expiration date of the lot/batch: May 2001
- Purity test date: 18 March 1999
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:at room temperature, light and humidity protected
- Stability under test conditions: Stable for 4 hours in vehicle at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: at maximum dose used : 100 mg/ml
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The mixtures of the test article and vehicle were prepared daily before administration. The test article was weighed into a glass beaker on a tared precision balance and the vehicle added (w/v).The mixtures were prepared using a homogenizer. During the daily administration period, the homogeneity was maintened using a magnetic stirrer
Test animals
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- WIST HanIbm
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: RCC Ltd. Biotechnology and Animal Breeding Division
- Age at study initiation: 11 weeks minimum
- Weight at study initiation: 191 to 243 grams
- Fasting period before study: not specified
- Housing: Animals were housed individually in Makrolon cages (type-3) with wire mesh tops and standardized granulated softwood beddings
- Diet (e.g. ad libitum): Pelleted standard Kliba 3433 rat/mouse maintenance diet (Provimi Kliba AG, Switzerland), ad libitum
- Water (e.g. ad libitum):tap water in bottles ad libitum
- Acclimation period: at least ten days prior to pairing under test conditions
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3 deg Celsius
- Humidity (%): 40+-70% relative humidity
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12h/12h with background music played at a centrally defined low volume for at least 8 hours during the light period
IN-LIFE DATES: From: To:
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 1% diluted in bi-distilled water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The mixtures of the test article and vehicle were prepared daily before administration. The test article was weighed into a glass beaker on a tared precision balance and the vehicle added (w/v).The mixtures were prepared using a homogenizer. During the daily administration period, the homogeneity was maintened using a magnetic stirrer
VEHICLE
- Justification for use and choice of vehicle (if other than water): no information
- Concentration in vehicle: 10, 30 and 100 mg/ml of test item in vehicle
- Amount of vehicle (if gavage): 10ml/kg
- Lot/batch no. (if required): no information
- Purity: no information - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- During the course of the study, samples for confirmation of concentration, homogeneity and stability were taken during the forst and the last week of the treatment period. Samples were taken immediately after preparation and again 4 hours later. Analysis were performed using a High Performance Liquid Chromatography HPLC method.
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/1
- Length of cohabitation: overnight
- Further matings after two unsuccessful attempts: no
- Verification of same strain and source of both sexes: not specified, supplied by RCC, no more details provided
- Proof of pregnancy: vaginal plug and copulation plug referred to as day 0 of pregnancy
- Duration of treatment / exposure:
- 12 days ( day 6 to day 17 of pregnancy)
- Frequency of treatment:
- Daily
- Duration of test:
- 17 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 22 females per dose were used
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: no information
- Rationale for animal assignment (if not random):computer-generated random algorithm
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least twice daily for signs of reaction to treatment and/or symptoms off ill heath
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: Body weight were recorded daily from day 0 until day 21 post coitum
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
Food consumption was recorded for the following periods : days 0-6, 6-12, 12-18, 18-21 post coitum
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No : calculated for grams/animal/day
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day #21
- Organs examined: all internal organs, with emphasis on the uterus, uterine contents, position of the fetuses in the uterus and number of corpora lutea
- Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: No
- Number of late resorptions: No - Fetal examinations:
- - External examinations: Yes :all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes :half per litter
- Head examinations: No data - Statistics:
- The following statistical methods were used to analyse the body weights, food consumption, reproduction and skeletal examination data:
-Means and standard deviations of various data were calculated and included in the report
-If the variables could be assumed to follow a normal distribution, The Dunnett many-one t-test, based on a pooled variance estimate, was used for intergroup commparisons (i.e. single treatment groups against the control group)
-The Steel test (many-one rank test) was applied when the data could not be assumed to follow a normal distribution
-Fisher's Exact test for 2x2 tables was applied if the variables could be dichotomized without loss of information.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- Dark discolored feces was noted from day 7 post coitum (second day of the treatment) until day 18 post coitum il all females of the high dose level group. No further signs or reactions to treatment were observed in any female of any group.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Description (incidence):
- No female died during the course of this study.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- The mean bodyweight gain in all groups was similar during the entire study. Further, the mean corrected body weight gain (corrected for uterus weight) gave no indication for test article-related effects.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- There were no test article-related differences amongst the mean food consumption of group 1, and all the treated groups.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In two females which had no fetuses in the high dose level group, the uterine horns contained fluid (a common finding in female rats of the strain and age). No further abnormal macroscopical findings were noted in group 4 and ni macroscopical changes were noted in the females of group 1, 2 or 3.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- effects observed, non-treatment-related
- Description (incidence and severity):
- One female of group 2 (100 mg/kg/day) had only empty implantation sites. These finding was considered to be incidental.
- Description (incidence and severity):
- a further female in group of 100 mg/kg/day only embryonic resoptions at caesarian section on day 21 post coitum. These finding was considered to be incidental.
- Early or late resorptions:
- not examined
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed - Changes in number of pregnant:
- no effects observed
- Other effects:
- not examined
- Details on maternal toxic effects:
- There were 20 to 22 pregnant females per group. In the group who received 100 mg/kg/day one female had only embryonic resorptions and in the highest dose group two females were not pregnant, one female had only empty implantation sites and a further one only embryonic resorptions at Caesarean section. These findings were considered to be incidental as a dose relation was missing. No deaths were reported, and clinical signs were limited to discoloured faeces at 1000 mg/kg/day.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
- mortality
- pre and post implantation loss
- total litter losses by resorption
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Effect observed but no significant.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not examined - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- In group 1 (control), 2 (100 mg/kg/day), 4 (1000 mg/kg/day) the sex ratio of fetuses was similar. In group 3 (300mg/kg/day), the number of males was increased and consequently the number of female reduced. The differences were within the range of th historical control data and considered to be incidental.
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Description (incidence and severity):
- In control gorup, one out 275 fetuses was noted with malformations as anal atresia and dysplastic tail.
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- During skeletal examination of the fetuses, abnormal findings were noted in all groups (including control and treated group). The type and frequencies of the common abnormal findings (wavy ribs, rudimentary cervical ribs, dumbbell shaped thoracic vertebral body, abnormally shaped sternebrae) gave no indication of test article-related effects.
- Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Only abnormal findings were observed in control group, group of 100 mg/kg/day and 1000 mg/kg/day as coagula in the head or thorax, and did not indicate test article-related effect and were considered to be incidental.
- Other effects:
- not examined
- Details on embryotoxic / teratogenic effects:
- No effects on litter parameters or foetal weight were observed. Foetal and litter incidences of external, soft tissue and skeletal anomalies were similar for control and treated groups.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- changes in sex ratio
- fetal/pup body weight changes
- external malformations
- skeletal malformations
- visceral malformations
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
Table 1 :Summaryof reproductive data
|
|
Group 1 |
Group 2 |
Group 3 |
Group 4 |
|
Number of dams |
Mean |
22 |
21 |
22 |
18 |
|
Corpora Lutea |
N |
312 |
293 |
298 |
257 |
|
|
Mean |
14,2 |
14 |
13,5 |
257 |
|
|
Standard deviation |
1,8 |
1,8 |
1,8 |
1,5 |
|
Pre-implantationloss |
N |
15 |
22 |
15 |
20 |
|
|
% of corp.Lutea |
4,8 |
7,5 |
5 |
7,8 |
|
|
Mean |
0,7 |
1 |
0,7 |
1,1 |
|
|
Standard deviation |
1,1 |
1,3 |
0,9 |
1,3 |
|
|
Number of dams affected |
8 |
10 |
9 |
10 |
|
Implantation site |
N |
297 |
271 |
283 |
237 |
|
|
% of corp.Lutea |
95,2 |
92,5 |
95 |
92,2 |
|
|
Mean |
13,5 |
12,9 |
12,9 |
13,2 |
|
|
Standard deviation |
1,7 |
2 |
1,7 |
1,6 |
|
Post-implantationloss |
N |
22 |
14 |
22 |
13 |
|
|
% of implantation sites |
7,4 |
5,2 |
7,8 |
5,5 |
|
|
Mean |
1 |
0,7 |
1 |
0,7 |
|
|
Standard deviation |
1,5 |
0,8 |
1,4 |
1,1 |
|
|
Number of dams affected |
11 |
10 |
11 |
7 |
|
Implantation sitescars |
N |
0 |
0 |
0 |
0 |
|
Embryonic/fetal deaths total |
N |
22 |
14 |
22 |
13 |
|
Embryonic resorptions |
N |
20 |
14 |
21 |
11 |
|
|
% of implantation sites |
6,7 |
5,2 |
7,4 |
4,6 |
|
|
Mean |
0,9 |
0,7 |
1 |
0,6 |
|
|
Standard deviation |
1,5 |
0,8 |
1,5 |
1,1 |
|
|
Number of dams affected |
10 |
10 |
10 |
5 |
|
Fetalresorptions |
|
2 |
0 |
1 |
2 |
|
Fetuses |
Totalfetuses |
N |
275 |
257 |
261 |
224 |
|
% of implantation sites |
92,6 |
94,8 |
92,2 |
94,5 |
|
|
Mean |
12,5 |
12,2 |
11,9 |
12,4 |
|
|
Standard deviation |
1,7 |
1,9 |
2,1 |
2,1 |
|
Live fetuses |
N |
275 |
257 |
261 |
224 |
|
Abnormal fetuses |
|
1 |
0 |
0 |
0 |
|
|
% offetuses |
0,4 |
|
|
|
|
|
Mean |
0 |
|
|
|
|
|
Standard deviation |
0,2 |
|
|
|
|
|
Numberofdamsaffected |
1 |
|
|
|
|
|
Abnormal live fetuses at external examination |
1 |
0 |
0 |
0 |
|
|
Abnormal dead fetuses at external examination |
0 |
0 |
0 |
0 |
|
Number of dams |
N |
22 |
21 |
22 |
18 |
|
Sex of fetuses |
Total male |
129 |
124 |
143 |
100 |
|
|
% offetuses |
46,9 |
48,2 |
54,8# |
44,6 |
|
|
Mean |
5,9 |
5,9 |
6,5 |
5,6 |
|
|
Standard deviation |
1,5 |
2,1 |
2,1 |
1,9 |
|
|
totalfemale |
146 |
133 |
118 |
124 |
|
|
% offetuses |
53,1 |
51,8 |
45,2# |
55,4 |
|
|
Mean |
6,6 |
6,3 |
5,4 |
6,9 |
|
|
Standard deviation |
1,7 |
1,8 |
1,6 |
2,2 |
|
|
Live males |
129 |
124 |
143 |
100 |
|
|
Livefemales |
146 |
133 |
118 |
124 |
|
Weights of fetuses (litter basis) |
Total fetuses |
N (liters) |
22 |
21 |
22 |
18 |
|
Mean |
4,6 |
4,7 |
4,8 |
4,7 |
|
|
Standard deviation |
0,3 |
0,3 |
0,3 |
0,3 |
|
males |
N (litters) |
22 |
21 |
22 |
18 |
|
|
Mean |
4,7 |
4,8 |
4,9* |
4,9 |
|
|
Standard deviation |
0,3 |
0,3 |
0,3 |
0,3 |
|
females |
N (litters) |
22 |
21 |
22 |
18 |
|
|
Mean |
4,5 |
4,6 |
4,6 |
4,6 |
|
|
|
Standard deviation |
0,3 |
0,3 |
0,3 |
0,3 |
Weights of fetuses (fetuses basis) |
total fetuses |
n (fetuses) |
275 |
257 |
261 |
224 |
|
Mean |
4,6 |
4,7** |
4,8** |
4,7** |
|
|
Standard deviation |
0,4 |
0,4 |
0,4 |
0,4 |
|
males |
n (fetuses) |
129 |
124 |
143 |
100 |
|
|
Mean |
4.7 |
4,9** |
4,9** |
4,9** |
|
|
Standard deviation |
0,4 |
0,4 |
0,4 |
0,3 |
|
females |
n (fetuses) |
146 |
133 |
118 |
124 |
|
|
Mean |
4,5 |
4,6** |
4,6* |
4,6 |
|
|
Standard deviation |
0,3 |
0,4 |
0,4 |
0,4 |
*/** Dunett's based on pooled variance significant at a level 5%* or 1%**
# Fisher's exact test significant at level 5% # or 1% ##
Applicant's summary and conclusion
- Conclusions:
- Under experimental condtion of this study, the registered substance External D&C Violet No. 2 did not induce toxic effect on rats and on embryo which were exposed during organogenesis. Hence, The No Observed Adverse Effect Level (NOAEL) for teratogenicity and maternal toxicity was defined as 1000mg/kg/day.
- Executive summary:
The purpose of the GLP compliant study was to detect effects on the pregnant female rats and development of the embryo and fetus consequent to exposure of the female rats to the test item according OECD Guideline 414 method.
The test substance (in 1% carboxymethylcellulose in water) was given daily at dose volumes of 10 ml/kg bw by oral gavage. The doses were selected on the basis of the results of a preliminary study in rats. Maternal evaluations and measurements included daily clinical signs and body weight/food intake recorded at designated intervals. The females were killed on gestation day 21, subjected to macroscopic examination, and foetuses were removed by Caesarean section. Common litter parameters were recorded and foetuses were sexed, weighed and submitted to external examination. About one half
of the fetuses were also examined for soft tissue anomalies whereas remaining fetuses were examined for skeletal anomalies following alizarin red staining.
There were 20 to 22 pregnant females per group. In the group who received 100 mg/kg/day one female had only embryonic resorptions and in the highest dose group two females were not pregnant, one female had only empty implantation sites and a further one only embryonic resorptions at Caesarean section. These findings were considered to be incidental as a dose relation was missing. No deaths were reported, and clinical signs were limited to discoloured faeces at 1000mg/kg/day. No effects on litter parameters or foetal weight were observed. Foetal and litter incidences of external, soft, tissue and skeletal anomalies were similar for control and treated groups.
Under experimental condtion of this study, the registered substance External D&C Violet No. 2 did not induce toxic effect on rats and on embryo which were exposed during organogenesis. Hence, The No Observed Adverse Effect Level (NOAEL) for teratogenicity and maternal toxicity was defined as 1000mg/kg/day.
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.