Registration Dossier

Administrative data

Description of key information

Repeated dose toxicity: via oral route;

NOAEL was considered to be < 1000 mg/kg bw/day for test chmical in male and female rat by oral gavage for subacute study.

Repeated dermal study;

The No Observed Adverse Effect Level (NOAEL) for the test compound D and C Red No. 7 is considered to be 130.6 mg/kg/day in male and female mice for 18 months

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
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
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Principles of method if other than guideline:
To evaluate the toxicity of test chemical in male and female rats by administrating the test chemical by gavage for 30 days.
GLP compliance:
not specified
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Pigment Red 57:1- Molecular formula (if other than submission substance): C18H14N2O6S.Ca- Molecular weight (if other than submission substance): 424.445 g/mole- Smiles notation (if other than submission substance): c12c(c(c(C(=O)[O-])cc1cccc2)O)\N=N\c1c(cc(C)cc1)S(=O)(=O)[O-].[Ca+2]- InChl (if other than submission substance): 1S/C18H14N2O6S.Ca/c1-10-6-7-14(15(8-10)27(24,25)26)19-20-16-12-5-3-2-4-11(12)9-13(17(16)21)18(22)23;/h2-9,21H,1H3, (H,22,23)(H,24,25,26);/q;+2/p-2/b20-19+;- Substance type: Organic -Supplier; ACNA
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Details on test animalTEST ANIMALS- Housing: The animals were housed under standardizedConditions.- Diet (e.g. ad libitum): pelleted standard diet ad libitum- Water (e.g. ad libitum): Water ad libitum- Acclimation period:
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Details on oral exposureVEHICLE- Justification for use and choice of vehicle (if other than water): In each study the control animals were dosed with an appropriate vehicle, chosen on the basis of the physicochemical properties of the product under test.- Concentration in vehicle: 1000 mg/kg bw/day- Amount of vehicle (if gavage): 10 ml/kg bw
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
30 days
Frequency of treatment:
Twenty two doses were given over a 30-day period. i.e., 5 times per week, one dose per day for 4 weeks plus Monday and Tuesday of the last week, no doses being given at theWeekends.
Remarks:
0 and 1000 mg/kg bw/day
No. of animals per sex per dose:
Total number of animals 400 mg/kg bw/day 20 (10 for recovery group)1000 mg/kg bw/day 20 (10 for recovery group)
Control animals:
yes, concurrent vehicle
Details on study design:
The study was preceded by an acute oral LDso determination of each test substance. In all cases the oral LD50 value in rats was in excess of 5000 mg/kg and no signs of toxicity were observed and therefore, a dose level of 1000 mg/kg body weight/day was selected for the subacute studies.
Positive control:
Not specified
Observations and examinations performed and frequency:
Observations and examinations performed & frequencyCAGE SIDE OBSERVATIONS: Not specified .DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: DailyBODY WEIGHT: Yes - Time schedule for examinations: DailyFOOD 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 - Time schedule for examinations: weekly- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: - Not specifiedFOOD 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: Not specifiedWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specifiedOPHTHALMOSCOPIC EXAMINATION: Not specifiedHAEMATOLOGY: Yes - Time schedule for collection of blood: At the end of the treatment and the recovery period, hematology was performed by standard methods on animals from control and test groups.- Parameters checked in table were examined as fallow Hematocrit, hemoglobin, erythrocytes count, total and differential leucocyte counts, median cell volume, median cell hemoglobin, platelet count, prothrombin time.CLINICAL CHEMISTRY: Yes - Time schedule for collection of blood: At the end of the treatment and the recovery period clinical chemistry was performed by standard methods on animals from control and test groups.- Parameters checked in table were examined as fallow serum alkaline phosphatase (SAP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT).URINALYSIS: Yes - Time schedule for collection of urine: At the end of the treatment and the recovery period urine analysis was performed by standard methods on animals from control and test groups.- Metabolism cages used for collection of urine: Yes - Parameters checked were examined as fallow volume, color, pH, specific gravity, bilirubin, quantitative glucose, quantitative protein, urobilinogen, and urea as well as analysis of thesediment.NEUROBEHAVIOURAL EXAMINATION: Not specified Other;Organ weight; Organ weights were determined for selected organs, including liver, kidneys, adrenals, and spleen.
Sacrifice and pathology:
Sacrifice and pathologyGROSS PATHOLOGY: Yes, At the end of the treatment period or after the recovery period, each rat was examined externally and by dissection for macroscopic abnormalities. Each rat wasautopsied and selected organs, including liver, kidneys, adrenals, and spleen were observed.HISTOPATHOLOGY: Yes, At the end of the treatment period or after the recovery period, selected organs, including liver, kidneys, adrenals, and spleen were submitted for histopathological examination, following determination of the organ weights. Other organ tissues were fixed in formalin and are held for reference in the archives.
Statistics:
Appropriate statistical analyses were performed on the different measurements.
Clinical signs:
no effects observed
Description (incidence and severity):
Other then Red colored feces ,no statically significant effect were observed at the dose level of 1000 mg/kg bw/day in trated group compare to control.
Mortality:
no mortality observed
Description (incidence):
No statically significant mortality were observed at the dose level of 1000 mg/kg bw/day in trated group compare to control.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Significant effect were observed at the dose level of 1000 mg/kg bw/day in trated group compare to control. But reversible effct were observed in recovery animals.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No statically significant effects were observed at the dose level of 1000 mg/kg bw/day in trated group compare to control.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
No statically significant effects were observed at the dose level of 1000 mg/kg bw/day in trated group compare to control.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
No statically significant effects were observed at the dose level of 1000 mg/kg bw/day in trated group compare to control.
Urinalysis findings:
no effects observed
Description (incidence and severity):
No statically significant effects were observed at the dose level of 1000 mg/kg bw/day in trated group compare to control.
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Increased kidney weight were observed at 1000 mg/kg bw/day in trated group compare to control. But reversible effct were observed in recovery animals.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No statically significant effects were observed at the dose level of 1000 mg/kg bw/day in trated group compare to control.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Changes in tubules of kidneys were observed at 1000 mg/kg bw/day in trated group compare to control. But reversible effct were observed in recovery animals.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Key result
Dose descriptor:
NOAEL
Effect level:
<= 1 000 other: mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No statically significant effect were observed at this dose
Remarks on result:
other: No toxic effct were observed
Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Conclusions:
NOAEL was considered to be < 1000 mg/kg bw/day for test chmical in male and female rat by oral gavage for subacute study.
Executive summary:

Subacute study of test chemical was assessed for its possible toxic potential. For this purpose The test chemical was administrated by oral gavage to 20(10 for recovery group) male and female rats by using test concentration of0 and1000 mg/kg/day. The animals were observed for clinical sign, mortality, food consumption, body weight, haematology, clinical chemistry, urine analysis, gross pathology and histopathology. No mortality was observed at treated group 1000 mg/kg/day. Significant effect were observed for body weight and histopatholgy at the dose level of 1000mg/kg bw/day in treated group compare to control. But reversible effect were observed in recovery animals. No significant effect were observed at this dose. Therefore NOAEL was considered to be < 1000mg/kg bw/day for test chemical in male and female rat by oral gavage for subacute study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
K2 data from qulified publication

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed publication
Qualifier:
according to
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Combined repeated dose and carcinogenicity study by the dermal route was performed to determine the dermal toxic nature of the test chemical D & C Red no.7 upon repeated application.
GLP compliance:
not specified
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): D & C Red no.7- Molecular formula (if other than submission substance): C18H14N2O6S.Ca- Molecular weight (if other than submission substance): 424.445 g/mole- Smiles notation (if other than submission substance): c12c(c(c(C(=O)[O-])cc1cccc2)O)\N=N\c1c(cc(C)cc1)S(=O)(=O)[O-].[Ca+2]- InChl (if other than submission substance): 1S/C18H14N2O6S.Ca/c1-10-6-7-14(15(8-10)27(24,25)26)19-20-16-12-5-3-2-4-11(12)9-13(17(16)21)18(22)23;/h2-9,21H,1H3, (H,22,23)(H,24,25,26);/q;+2/p-2/b20-19+;- Substance type: Organic - Physical state: Solid - Analytical purity: 98%- Impurities (identity and concentrations): 2%
Species:
mouse
Strain:
ICR
Remarks:
(Swiss Webster derived)
Details on species / strain selection:
No data
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Swiss Webster derived- Age at study initiation: No data- Weight at study initiation: No data- Fasting period before study: No data available- Housing: Each animal was assigned an identification number and individually housed in a supported wire cage.- Diet (e.g. ad libitum): Ad libitum- Water (e.g. ad libitum): Ad libitum- Acclimation period: No data availableENVIRONMENTAL CONDITIONS- Temperature (°C): No data available- Humidity (%):No data available- Air changes (per hr): No data available- Photoperiod (hrs dark / hrs light): No data availableIN-LIFE DATES: From: To: No data available
Type of coverage:
open
Vehicle:
other: Distilled water
Details on exposure:
TEST SITE- Area of exposure: 6 cm²- % coverage: No data available- Type of wrap if used: No data available- Time intervals for shavings or clipplings: Subsequent periodic clipping was performed according to the rate of hair growthREMOVAL OF TEST SUBSTANCE- Washing (if done): No data available- Time after start of exposure: No data availableTEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.1 ml of the vehicle containing 0 or 128.5 mg test material- Concentration (if solution): 0 or 128.5 mg- Constant volume or concentration used: yes- For solids, paste formed: no data availableVEHICLE- Justification for use and choice of vehicle (if other than water): Distilled water- Amount(s) applied (volume or weight with unit): 0.1 ml- Concentration (if solution): 0.1 ml of the vehicle containing 0 or 128.5 mg test material- Lot/batch no. (if required): No data- Purity: no data availableUSE OF RESTRAINERS FOR PREVENTING INGESTION: no data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data available
Duration of treatment / exposure:
471 days
Frequency of treatment:
Twice weekly
Remarks:
0 or 130.6mg/kg/day
No. of animals per sex per dose:
Total: 500130.6 mg: 50 males and 50 females0 mg/Kg bw: 150 males and 50 femalesPositive control: 50 males and 50 females
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Preliminary to establishing the dosages for the skin painting studies, the amounts of lipstick ingested by women was established in a study utilizing female volunteers- Rationale for animal assignment (if not random): No data available- Rationale for selecting satellite groups: No data available- Post-exposure recovery period in satellite groups: No data available- Section schedule rationale (if not random): No data available
Positive control:
3, 4-benzpyrene,, dissolved in acetone
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes - Time schedule: daily- Cage side observations checked in table [No.?] were included. MortalityDETAILED CLINICAL OBSERVATIONS: Yes- Time schedule: Twice weekly for gross toxicityBODY WEIGHT: no data- Time schedule for examinations: no dataFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): no data- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No dataFOOD EFFICIENCY: No data- 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 dataWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data- Time schedule for examinations: No dataOPHTHALMOSCOPIC EXAMINATION: No data - Time schedule for examinations:- Dose groups that were examined: No dataHAEMATOLOGY: No data- Time schedule for collection of blood: No data- Anaesthetic used for blood collection: No data- Animals fasted: No data- How many animals: No data- Parameters checked in table [No.?] were examined.DERMAL IRRITATION (if dermal study): No data- Time schedule for examinations: No dataCLINICAL CHEMISTRY: No data- Time schedule for collection of blood: No data- Animals fasted: No data - How many animals: No data- Parameters checked in table [No.?] were examined.URINALYSIS: No data- Time schedule for collection of urine: No data- Metabolism cages used for collection of urine: No data - Animals fasted: No data- Parameters checked in table [No.?] were examined.NEUROBEHAVIOURAL EXAMINATION: No data- Time schedule for examinations:- Dose groups that were examined:- Battery of functions tested: No data sensory activity / grip strength / motor activity / other: No dataOTHER:
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, Animals that died, those sacrificed moribund, and those surviving the 18-month experimental period were necropsied and the tissues including those of the brain, pituitary, thyroid, thymus, liver, spleen, kidney, adrenal, stomach, small intestines, large intestines, urinary bladder, axillary lymph nodes, testes, ovary, skin from area of treatment, any tissue masses, grossly abnormal organs, or tissues were preserved in 10% formalinHISTOPATHOLOGY: Yes, tissues were sectioned, stained with hematoxylin and eosin, and examined. These included skin and any grossly abnormal organs andtissues of all animals in the color experimental group; skin and any grossly abnormal organs and tissues of approximately 50 vehicle control animals (approximatelyequal number of males and females); complete pathology on five males and five females randomly selected vehicle control animals that survived the 18-month experimentalperiod; and complete pathology on five males and five females randomly selected vehicle control animals that survived the 18-month experimental period; and completepathology of five male and five female animals from the positive control group that included induced skin lesions.
Other examinations:
No data available
Statistics:
Yes ,Mean was observed
Clinical signs:
not specified
Dermal irritation:
not specified
Mortality:
mortality observed, treatment-related
Description (incidence):
Mortality: The percent survival of the treated mice changed with the duration of the treatment. The survival was 97% in 4 months, 92% in 10 months, 69% in 12 months and 41% in 18 months respectively.
Body weight and weight changes:
not specified
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
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
Histopathology: The incidence of extramedullary hematopoesis of the spleen (5 male and 9 females: 14%) in the test group was consistent with that found in the distilled water vehicle control groups. The incidence in the three distilled water control groups was 13 % , 18 % , and 22 % for a mean of 17.7 % . The test group did not show a greater incidence than a control group.The incidence of ectoparasitism was greater in the dye treated group than found in the vehicle controls. This increase in skin mite infestation may have contributed to the increase in epidermal change dermatitis, acanthosis, and hyperkeratosis observed in the dye treated groups.Although the number of neoplasias involving the mammary glands or internal organs was noted in the test group, there was, however, no apparent change in their pattern which could be attributed to the dermal application of the test dye compound.The incidence and severity of lesions of interstitial nephritis, cystitis, amyloidosis, and bronchopneumonia though observed in the test groups but there were no significant variations that could be attributed to application of the test compound.
Other effects:
not specified
Key result
Dose descriptor:
NOAEL
Effect level:
130.6 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
gross pathology
histopathology: neoplastic
Critical effects observed:
not specified

Table: Percent survival of mice

Months

5

10

16

18

D & C Red no 7

92

88

69

48

 

Table: Details of microscopic analysis

Animal

Number

Experimental Days Observed

Location of Lesion

Microscopic Diagnosis

3F

485

Tissue mass beneath the dorsal skin treatment

area (appeared to be attached to the spine)

Rather large cells with vacuolated cytoplasm and pyknotic nuclei postmortem autolysis prevented positive identification

21F

568

Tissue mass in intestine

 

Reticulam cell sarcoma

36F

568

Tissue mass in near pituitary

Abscess involving the brain and pituitary

39F

569

Nodule on liver

Reticulam cell sarcoma

40F

473

Tissue mass near tritrigerminal nerve

Mass was relatively compact bone contaningspaceswith hematogenic activity

55M

502

 

Tissue mass in near pituitary

Abscess involving pituitary

75M

446

 

Nodule on kidney

Focal granulomatous process

88M

569

Tissue mass in liver

 Hepatic cell adenoma

 93M  569   

Tissue mass in liver

 Hepatic cell adenoma 
 100M  569  Nodule in kidney  Hepatic cell adenoma
Conclusions:
The No Observed Adverse Effect Level (NOAEL) for the test compound D and C Red No. 7 is considered to be 130.6 mg/kg/dayin male and female mice for 18 months
Executive summary:

Repeated dose toxicity by the dermal route was performed to determine the dermal toxic nature of the test compoundD & C Red no. 7upon repeated application. The test chemical was applied to the clipped dorsal area mice. The animals were observed for mortality, clinical signs and gross pathology and histopathology was performed.

Repeated dermal application of 0.1 ml containing 1 mg of dye applied to the dorsal area of ICR (Swiss Webster derived) white mice twice weekly for 18 months failed to produce any adverse effects and hence the No Observed Adverse Effect Level (NOAEL) for the test compoundD & C Red no. 7 is found to be130.6 mg/kg/day in ICR male and female mouse by 18 months of repeated dermal application.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
130.6 mg/kg bw/day
Study duration:
chronic
Species:
mouse
Quality of whole database:
K2 data from qualified publication

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose toxicity: via oral route;

Experimental studies was reviewed to determine the toxic nature of target substance calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (5281-04-9 ) , Common name; Pigment Red 57:1 and Litholrubine BK upon repeated exposure by oral route. The studies are mentioned below:

 Repeated dose oral experimental study was performed by K. H. Leist (Ecotoxicology And Environmental Safety,1982) to determine the toxic nature of calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (5281-04-9 ) , Common name; Pigment Red 57:1 and Litholrubine BK by using rodent animals. Subacute study of test chemical was assessed for its possible toxic potential. For this purpose test chemical was administrated by oral gavage to 20(10 for recovery group) male and female rats by using test concentration of0 and1000 mg/kg/day. The animals were observed for clinical sign, mortality, food consumption, body weight, haematology, clinical chemistry, urine analysis, gross pathology and histopathology. No mortality was observed at treated group 1000 mg/kg/day. Significant effect was observed for body weight and histopatholgy at the dose level of 1000mg/kg bw/day in treated group compare to control. But reversible effect were observed in recovery animals. No significant effect were observed at this dose. Therefore NOAEL was considered to be < 1000mg/kg bw/day for test chemical in male and female rat by oral gavage for subacute study.

Supported by other experimental study, which was observed by National Institute of Technology and Evaluation(jcheck,2018) to determine the toxic nature of calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (5281-04-9 ) , Common name; Pigment Red 57:1 and Litholrubine BK by using rodent animals. Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test of test chemical was assessed for its possible toxiv potential.For this purpose Sub chronic study was performed according to OECD guideline 422. The test chemical was administrated by oral gavage to 13 male and female Crj: CD(SD)rats by using test concentration of0,100, 300 and 1000 mg/kg/day. The animals were observed forclinical sign, mortality, food consumption, body weight, haematology, clinical chemistry, gross pathology and histopathology. No mortality was observed at all treated group,100, 300 and 1000 mg/kg/day. Statistically significant effect was observed at the300 and 1000 mg/kg bw/day group animals in heamotology, clinical chemistry and organ weight. Degeneration or necrosis of renal tubular epithelial cells of the cortex was observed in 3 out of 5 males in the 1000 mg / kg administration group. In these examples, the cavity of the degenerated tubule was dilated, and in one case of the medulla showing the strongest change, eosin light stain which seems cytopathic substance was contained in the cavity of some collecting tubes It was. In one other case, renal tubular epithelium degeneration was not observed, but extremely slight expansion of renal tubular cavity was observed. In females of the test substance-administered group, only mild degeneration of renal tubular epithelium was observed in one case. In addition, only a few regenerated renal tubules were found in the sexes of the control group and the test substance administered group. No statically significant effct were observed at 100 mg/kg/day group. Therefore NOEL was considered to be100 mg/kg/day for males and less than 100 mg/kg/day for females for test chemical.

Supported by another experimental study, which was observed by European Food Safety Authority (EFSA) (EFSA Journal,2010) to determine the toxic nature of calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (5281-04-9 ) , Common name; Pigment Red 57:1 and Litholrubine BK by using non rodent animals. Sub chronic study of test chemical was assessed for its possible toxic potential. For this purpose The test chemical was administrated to 1 male and 1 female dog by oral feed at the concentration of125, 250, 375 and 500 mg/kg bw/day. The test chemical was feeded as fallow to the test animal

 

0.5% (weeks 1 and 2), 125mg/kg bw/day

1.0% (weeks 2 and 3), 250mg/kg bw/day

1.5% (weeks 5-10) 375mg/kg bw/day

2% (weeks 11-13)500mg/kg bw/day

The animals were observed for clinical sign. Significant effect as diarrhoea was observed a few days before the dose was increased to 375mg/kg bw/day treated group compare to control. Significant effect as vomiting was observed a few days before the dose was increased to 500mg/kg bw/day treated group compare to control. No significant effects were observed at the dose level of125 and 250 mg/kg bw/day treated group compare to control. Therefore NOAEL was considered to be 250mg/kg bw/day for test chemical in male and female dogs by oral feed for subchronic study.

Based on the data available for the target chemical calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (5281-04-9 ) , Common name; Pigment Red 57:1 and Litholrubine BK , D & C Red no. 7 does not exhibit toxic nature upon repeated exposure by oral route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

 

 

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (5281-04-9 ) , Common name; Pigment Red 57:1 and Litholrubine BK . Also considering the particle size distribution of the substance the majority of the particles was found to be in the size of 150 micron to 53 micron which is much larger size range compared to the inhalable particulate matter Thus, exposure to inhalable dust, mist and vapour of the chemical calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate is highly unlikely. Therefore this study is considered for waiver.

 

Repeated dermal study

Experimental study was reviewed to determine the toxic nature of target substance calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (5281-04-9 ) , Common name; Pigment Red 57:1 and D & C Red no. 7 upon repeated exposure by dermal route. The studies are mentioned below:

 Repeated dose dermal experimental study was performed by Steven Carson (J. Toxicol. Cut. & Ocular Toxicol., 1984) to determine the toxic nature of calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (5281-04-9 ) , Common name; Pigment Red 57:1 and Litholrubine BK by using rodent animals. Repeated dose toxicity by the dermal route was performed to determine the dermal toxic nature of the test compoundD & C Red no. 7upon repeated application. The test chemical was applied to the clipped dorsal area mice. The animals were observed for mortality, clinical signs and gross pathology and histopathology was performed. Repeated dermal application of 0.1 ml containing 1 mg of dye applied to the dorsal area of ICR (Swiss Webster derived) white mice twice weekly for 18 months failed to produce any adverse effects and hence the No Observed Adverse Effect Level (NOAEL) for the test compound D & C Red no. 7 is found to be130.6 mg/kg bw/day in ICR male and female mouse by 18 months of repeated dermal application.

Based on the data available for the target chemical calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (5281-04-9 ) , Common name; Pigment Red 57:1 and Litholrubine BK , D & C Red no. 7 does not exhibit toxic nature upon repeated exposure by dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (5281-04-9 ) , Common name; Pigment Red 57:1 and Litholrubine BK , D & C Red no. 7 does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.