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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic 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

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:
not specified
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium 4-[(2-hydroxy-1-naphthyl)azo]benzenesulphonate
EC Number:
211-199-0
EC Name:
Sodium 4-[(2-hydroxy-1-naphthyl)azo]benzenesulphonate
Cas Number:
633-96-5
Molecular formula:
C16H12N2O4S.Na
IUPAC Name:
sodium 4-[(2-hydroxy-1-naphthyl)azo]benzenesulphonate

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Strain: Wistar
HanIbm: WIST (SPF)
Body weight males: mean 141 g (123-163 g)
Body weight females: mean 123 g (98-143 g)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: water + 1% CMC
Duration of treatment / exposure:
7 days per week for at least 13 weeks
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
2.5 mg/kg bw
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
5 mg/kg bw
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
10 mg/kg bw
Basis:
nominal in diet
No. of animals per sex per dose:
10 male and 10 females for each concentration
Control animals:
yes, concurrent no treatment

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
No mortality and no clinical signs were observed.
Mortality:
mortality observed, treatment-related
Description (incidence):
No mortality and no clinical signs were observed.
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
see "details on results"
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
see "details on results"
Details on results:
Changes in haematology were evident in males treated with 5 and 10 mg/kg bw/day.
Changes in haematological parameters like increased methemoglobin levels in males up to 2.5 mg/kg bw/day and females up to 5 mg/kg bw/day, decreased haemoglobin levels in males (5 and 10 mg/kg bw/day) increased reticulocyte counts (relative and absolute) in all test article treated males and a general shift towards high fluorescent reticulocytes in high dosed males.
The changes noted in methemoglobin levels and reticulocte counts in males treated with 2.5 mg/kg bw/day were within the upper levels of the historical control data.
When compared with similarly high values at 5 mg/kg bw/day, there was no correlation to pathomorphological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.
In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day.
No test article related macroscopic findings were observed during necropsy.
With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day.
This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen.
The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors.

Effect levels

Dose descriptor:
NOAEL
Effect level:
2.5 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The value of NOAEL for repeated dose toxicity was established at 2.5 mg/kg bw/day both for males and females.
Based on the test result, Acid Orange 7 needs to be considered as toxic for oral repeated dose with classiifcation under CLP as Cat. 1 STOT RE, H372: Causes damage to organs through prolonged or repeated exposure
Executive summary:

The value of NOAEL for repeated dose toxicity was established at 2.5 mg/kg bw/day both for males and females.

It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed.

Even if there are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. Based on the test result, Acid Orange 7 needs to be considered as toxic for oral repeated dose with classification under CLP as Cat. 1 STOT RE, H372: Causes damage to organs through prolonged or repeated exposure.