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Toxicological information

Repeated dose toxicity: oral

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Administrative data

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

Data source

Reference
Reference Type:
publication
Title:
Subacute Toxicity Studies of Selected Organic Colorants
Author:
K. H. Leist
Year:
1982
Bibliographic source:
Ecotoxicology And Environmental Safety 6, 457-463 (1982)

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report): 2-Naphthalenecarboxylic acid, 3-hydroxy-4-[(4-methyl-2-sulfophenyl)azo]-, calcium salt- 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: 87%- Impurities (identity and concentrations): 13%
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

Test animals

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:

Administration / exposure

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.
Doses / concentrations
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

Examinations

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.

Results and discussion

Results of examinations

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

Effect levels

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

Target system / organ toxicity

Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

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.