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EC number: 415-510-2 | CAS number: 145703-76-0
- 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 (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- from February 10 to April 4, 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Test conducted according to internationally accepted guidelines.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- (2015)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3500 (Preliminary Developmental Toxicity Screen)
- Version / remarks:
- (2000)
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- Red GS 3848
- IUPAC Name:
- Red GS 3848
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALSSource: Toxi-Coop Zrt.Age at study initiation: 105-110 daysWeight at study initiation: 357-433 g for males, 210-255 g for femalesHousing: before mating 2 animals of same sex/cage, at mating 1 male and 1 female/cage, pregnant females individually, males afetr mating 2 animals/cageDiet: ad libitumAcclimation period: 35 daysENVIRONMENTAL CONDITIONSTemperature: 22 ± 3 °CHumidity: 30-70 %Air changes: above 10 per hour by a central air-condition systemPhotoperiod: artificial light from 6 a.m. to 6 p.m
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: distilled water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Test substance was formulated in vehicle (distilled water) not longer than three days beforehand.VEHICLE: distilled waterConcentration in vehicle: 200, 60, 20 mg/mlAmount of vehicle: 5 ml/kg bwLot/batch no.: 1509-5529, 1511-5519, 1512- 5503, 1511-5526
- Details on mating procedure:
- M/F ratio per cage: 1 male and 1 female of the smale dose groulLength of cohabitation: until copulation occurredProof of pregnancy: vaginal plug and sperm in vaginal smear referred to as day 0 of pregnancy
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentration in dosing formulation was checked two times during the study and found to vary between 97 % and 107 % of nominal values. Suitability of chosen vehicle (recovery and stability) for test item at intended concentrations was analytically verified up front.
- Duration of treatment / exposure:
- Test item and vehicle were orally administered daily (7 days per week) for a whole period of 51-54 days. Dosing begun after acclimatisation (35 days) and included: -males: 14 days pre-mating period, 1-4 days mating period, 33-36 days post-mating period. -females: 14 days pre-mating period, 1-4 days mating period, 22-23 days gestation period, 13-15 days lactation period.
- Frequency of treatment:
- Daily (7 days per week).
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:100 mg/kg bw/dayBasis:nominal in water
- Remarks:
- Doses / Concentrations:300 mg/kg bw/dayBasis:nominal in water
- Remarks:
- Doses / Concentrations:1000 mg/kg bw/dayBasis:nominal in water
- No. of animals per sex per dose:
- 12/sex/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Dose selection rationale: chosen on the basis of the results of 28-day repeated dose oral toxicity test with test substance in rats, where dose of 1000 mg/kg bw/day was well tolerated. High dose chosen with the aim of inducing toxic effects but no mortality or severe suffering of animals. Low dose chosen to induce no toxic effect. Mid dose was interpolated geometrically.
Examinations
- Parental animals: Observations and examinations:
- DETAILED CLINICAL OBSERVATIONSGeneral observation, once a day after administration; detailed observation, at times of weekly weighing.Detailed examinations were carried out on skin, fur, eyes and mucous membranes, autonomic activity, circulatory and central nervous system, somatomotor activity and behaviour pattern, changes in gait, posture and response to handling. In addition, also tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma.BODY WEIGHTParental males weighed on first day of dosing (day 0) and weekly thereafter and on day of necropsy; parental females weighed on the firts day of dosing (day 0) then weekly, on gestation days 0, 7, 14 and 21 and on days 0 (within 24 h after parturition), 4 and 3 post-partum.FOOD CONSUMPTIONFood consumption for each animal determined weekly by reweighing non-consumed diet during treatment period except mating phase. For females food consumption was determined for pre-mating days 7, 13, gestation days 0, 7, 14, 21 and lactation days 0,4, 13.
- Oestrous cyclicity (parental animals):
- Examination of vaginal smears for 2 weeks before treatment initiation. Animals with 4-5 days cycles were included preferably in the study.
- Litter observations:
- PARAMETERS EXAMINED IN F1 OFFSPRINGNumber and sex of pups, stillbirths, live births, runts (pups significantly smaller than normal pups), presence of gross anomalies.Live pups weights on day 0, 4 and 13 post-partum. Any abnormal behaviour of offspring.Anogenital distance of each pup on day 4. Blood samples for possible determination of serum levels of thyroid hormones (T4): from at least 2 pups per litter on post-natal day 4 and day 13 (termination day).GROSS EXAMINATION OF DEAD PUPsOn day 0, lung flotation test to differentiate pups died intrauterine (stillborn) from pups died after birth (dead pups).In following days, necropsy by macroscopic examination of dead pups.
- Postmortem examinations (parental animals):
- SACRIFICEMales: day 51Females mated but non-pregnant: day 51Maternal animals: day 51-54GROSS NECROPSYAfter examination of external appearance, cranial, thoracic and abdominal cavities were opened and appearance of tissues and organs was observed, and any abnormality was recorded including details of location, color, shape and size. Special attention was paid to organs of the reproductive system. Number of implantation sites was recorded.ORGAN WEIGHTSBody weight, brain weight and weight of the testes and epididymides of adult animals; absolute organ weight and relative organ weight (to body and brain weight). Paired organs weighed together.HISTOPATHOLOGYFull histopathology examinations on preserved organs and tissues of the animals in the control and high dose groups with special emphasis on stages of spermatogenesis in the male gonads and histopathology of interstitial testicular cell structure and on the ovaries covering the follicular, luteal, and interstitial compartments of the ovary, as well as the epithelial capsule and ovarian stroma. Detailed histological examination on ovaries, uterus, vagina, pituitary, testes, epididymides, prostate and seminal vesicles with coagulating gland.Fixed tissues trimmed, processed, embedded in paraffin, sectioned with a microtome, placed on glass microscope slides, stained with hematoxylin and eosin and examined by light microscopy.
- Statistics:
- The statistical evaluation was performed with the statistical program package SPSS PC+4.0.The homogeneity of variance between groups was checked by Bartlett’s homogeneity of variance test. Where no significant heterogeneity was detected a one-way analysis of variance (ANOVA) is carried out. If the obtained result was significant, Duncan Multiple Range test was used to access the significance of inter-group differences. Getting significant result at Bartlett’s test, the Kruskal-Wallis analysis of variance was used and the inter-group comparisons were performed using Mann-Whitney U-test. Chi2 test was performed if feasible.Frequency of toxic response, pathological and histopathological findings by sex and dose was calculated.
- Reproductive indices:
- Copulatory index: measure of animals’ ability to mateMales = (no. of males with confirmed mating / total no. of males cohabited) × 100Females = (no. of sperm positive females / total number of femals cohabited) × 100 Fertility index: measure of male’s ability to produce sperm that can fertilize eggs and measure of female’s ability to become pregnant.Males = (no. of males impregnating a female / total no. of males with confirmed mating) × 100 Females = (no. of pregnant females / no. of sperm positive females) × 100 Gestation index: measure of pregnancy that provides at least one live pup(no. of females with live born pups / no. of pregnant females) × 100
- Offspring viability indices:
- Post-implantation/ pre-natal mortality (intrauterine mortality)100 × (no. of implantations - no. of liveborns) / no. of implantation Post-natal mortality /Extra-uterine mortality100 × (no. of liveborns - no. of live pups on PN13) / no. of livebornsSurvival Index 100 × no. of live pups on postnatal day 13 / no. of pups born Sex ratio100 × (no. of pups examined - no. of males (females)) / no. of pups examined
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- test item or metabolites detected in intestines
- Other effects:
- no effects observed
- Description (incidence and severity):
- Test substance intake: oral gavage
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Effect levels (P0)
open allclose all
- 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:
- other: systemic toxicity
- Dose descriptor:
- NOAEL
- Remarks:
- reproductive performance
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: gonad function, mating behaviour, conception
- Dose descriptor:
- NOAEL
- Remarks:
- raised post-implantation loss
- Effect level:
- 300 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: gonad function, mating behaviour, conception, parturition, post-natal loss
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
Details on results (F1)
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: development
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Under test conditions, the substance administered at 1000, 300 or 100 mg/kg bw/day by oral gavage did not cause signs of systemic toxicity and did not adversely influence the reproductive performance (gonad function, mating behaviour, conception, parturition) in parental male and female rats.Prenatal loss (post-implantation loss, percentage and mean) was slightly higher than in control group in dams at 1000 mg/kg bw/day. Although the slight difference with respect to control, a test item influence cannot be excluded. Development of F1 offspring was not impaired at any dose after repeated oral administration of dams from birth to post-natal day 13. Thus, NOAEL = 1000 mg/kg bw/day for systemic toxicity, reproductive performance of male, F1 offsprings; NOAEL = 300 mg/kg bw/day in females for post-implantation losses.
- Executive summary:
Method
Study on toxic potential of test item and its possible effects on reproduction and development when repeatedly administered orally (by gavage) to rats at doses of 1000, 300 and 100 mg/kg bw/day compared to control animals. As a screening test, it considered reproductive parameters such as gonadal function, mating behaviour, conception, pregnancy, parturition as well as development of F1 offspring from conception to day 13 post-partum, associated with administration of repeated maternal doses.
Groups of 12/sex animals, three dose groups and one control (only distilled water as vehicle).
Animals of parent (P) generation were dosed prior to mating (14 days) and throughout mating. After mating, males dosed up to 51 days and females up to 51 -54 days, including gestation period and lactation.
Results
At doses up to 1000 mg/kg bw/day, there was no substance-related mortality.; no clinical sign of systemic toxicity, no changes in body weight and body weight gain and no changes in food consumption were noted. No specific macroscopic alterations and no changes in weights of brain, testes and epididymes of males were seen at necropsy. No changes were noted after histopathological examinations of ovaries, uterus, vagina, pituitary, testes, epididymes, prostate and seminal vesicles with coagulating gland.
As for reproductive performance, no substance related effects on gonadal function, mating behaviour, conception, pregnancy, parturition up to 1000 mg/kg bw/day. Higher post implantation loss in comparison with control and historical control was noted at dose of 1000 mg/kg bw/day.
Based upon these results, no-observed-adverse-effect level was considered to be 300 mg/kg bw/day in rats when administered orally by gavage.
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