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Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from a secondary literature.

Data source

Reference
Reference Type:
other: Secondary Source
Title:
Combined dataset for the test chemical
Author:
SCCS
Year:
2007
Bibliographic source:
SCCP/1115/07

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Principles of method if other than guideline:
According to OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
GLP compliance:
not specified
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Hydrogen 3,6-bis(diethylamino)-9-(2,4-disulphonatophenyl)xanthylium, sodium salt
EC Number:
222-529-8
EC Name:
Hydrogen 3,6-bis(diethylamino)-9-(2,4-disulphonatophenyl)xanthylium, sodium salt
Cas Number:
3520-42-1
Molecular formula:
C27H30N2O7S2.Na
IUPAC Name:
sodium 4-[3,6-bis(diethylamino)-2,7-dimethylxanthenium-9-yl]benzene-1,3-disulfonate; 2-(3-diethylamino-6-diethylazaniumylidene-xanthen-9-yl)-5-sulfo-benzenesulfonate
Test material form:
not specified
Details on test material:
Name: C.I. Acid Red 52
CAS No.: 3520-42-1
Molecular Formula: C27-H30-N2-O7-S2.Na
Molecular Weight: 580.65 g/mol
SMILES: [Na+].CCN(CC)c1ccc2c(c3ccc(cc3S(=O)(=O)[O-])S(=O)(=O)[O-])c4ccc(cc4[o+]c2c1)N(CC)CC

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
No Data Available

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Homogenized bi-distilled water with 1% CMC
Details on oral exposure:
No Data Available
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No Data Available
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
Control Group
Dose / conc.:
100 mg/kg bw/day (nominal)
Remarks:
Low Dose Group
Dose / conc.:
300 mg/kg bw/day (nominal)
Remarks:
Mid Dose Group
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Remarks:
High Dose Group
No. of animals per sex per dose:
20 animals (10 males & 10 females) / dose level
Control animals:
yes, concurrent vehicle
Details on study design:
No Data Available
Positive control:
No Data Available

Examinations

Observations and examinations performed and frequency:
Animals were observed twice daily for mortality/morbidity and once daily for clinical abnormalities. Individual animal weights were recorded weekly. Body weight and food consumption were recorded weekly. Ophthalmologic evaluations on control and high-dose animals were performed at the end of the study. Haematology, clinical
chemistry and urinalysis evaluations were performed once during week 13.
Sacrifice and pathology:
At the end of the treatment period, all animals were killed and grossly examined. Selected organs were weighted. All animals were submitted to a complete macroscopic examination.
Other examinations:
No Data Available
Statistics:
No Data Available

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Clinical signs were restricted to discolorations of faeces and the mucosal surface of the stomach and/or intestines at ≥100 mg/kg and discolorations of the tail and paws at 1000 mg/kg.
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No significant changes in body weight or food intake were observed.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No significant changes in body weight or food intake were observed.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
no effects observed
Description (incidence and severity):
Ophthalmological findings were unremarkable.
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Male rats treated at 1000 mg/kg showed decreased fibrinogen levels.
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
Male rats treated at 1000 mg/kg showed slightly increased beta-globulin levels compared to the control group. Female rats treated at 1000 mg/kg showed decreased bilirubin levels and increased phospholipid levels compared to the control group. The observed biochemical changes lacked histopathologic correlates.
Urinalysis findings:
effects observed, non-treatment-related
Description (incidence and severity):
Decreased uric acid levels were observed at 300 mg/kg (females) and at 1000 mg/kg (both genders) compared to the control data.
Behaviour (functional findings):
effects observed, non-treatment-related
Description (incidence and severity):
Male rats treated at 1000 mg/kg showed slightly increased locomotor activity.
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
Clinical signs were restricted to discolorations of faeces and the mucosal surface of the stomach and/or intestines at ≥100 mg/kg and discolorations of the tail and paws at 1000 mg/kg. No significant changes in body weight or food intake were observed. Ophthalmological findings were unremarkable. Decreased uric acid levels were observed at 300 mg/kg (females) and at 1000 mg/kg (both genders) compared to the control data. Male rats treated at 1000 mg/kg showed slightly increased locomotor activity, decreased fibrinogen levels, and increased beta-globulin levels compared to the control group. Female rats treated at 1000 mg/kg showed decreased bilirubin levels and increased phospholipid levels compared to the control group. The observed biochemical changes lacked histopathologic correlates. Therefore, the biochemical changes were considered to be adaptive changes with no toxicological significance

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
behaviour (functional findings)
body weight and weight gain
clinical biochemistry
clinical signs
food consumption and compound intake
gross pathology
haematology
histopathology: non-neoplastic
mortality
ophthalmological examination
organ weights and organ / body weight ratios
urinalysis
Remarks on result:
not determinable due to absence of adverse toxic effects

Target system / organ toxicity

Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
Based on all the available data, it was concluded that the study-derived NOAEL was 1000 mg/kg bw/day.
Executive summary:

The read-across analogue hydrogen 3,6-bis(diethylamino)-9-(2,4disulphonatophenyl)xanthylium, sodium salt[CAS: 3520-42-1; EC: 222-529-8]has been tested for repeated dose toxicity according to OECD 408 (1998) as reported by the Scientific Committee on Consumer Products (SCCP/1115/07). The chemical was given by oral gavage to 10 rats per sex per dose level at 0 (vehicle), 100, 300 and 1000 mg/kg bw/day for a total of 13 weeks.No mortality was observed during the treatment period. Clinical signs were restricted to discolorations of faeces and the mucosal surface of the stomach and/or intestines at ≥100 mg/kg and discolorations of the tail and paws at 1000 mg/kg. No significant changes in body weight or food intake were observed. Ophthalmological findings were unremarkable. Decreased uric acid levels were observed at 300 mg/kg (females) and at 1000 mg/kg (both genders) compared to the control data. Male rats treated at 1000 mg/kg showed slightly increased locomotor activity, decreased fibrinogen levels, and increased beta-globulin levels compared to the control group. Female rats treated at 1000 mg/kg showed decreased bilirubin levels and increased phospholipid levels compared to the control group. The observed biochemical changes lacked histopathologic correlates. Therefore, the biochemical changes were considered to be adaptive changes with no toxicological significance. The study-derived NOAEL was 1000 mg/kg bw/day. The study was performed according to GLP.