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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:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes (incl. QA statement)
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
429-240-8
EC Name:
-
Cas Number:
212652-59-0
Molecular formula:
Hill formula: C25 H22 F N8 Na3 O13 S4 CAS formula: C25 H25 F N8 O13 S4 · 3 Na
IUPAC Name:
trisodium 3-amino-4-[2-(4-{[4-({2-[2-(ethenesulfonyl)ethoxy]ethyl}amino)-6-fluoro-1,3,5-triazin-2-yl]amino}-2-sulfophenyl)diazen-1-yl]-5-hydroxynaphthalene-2,7-disulfonate

Test animals

Species:
other: Rat, HanIbm (Wistar)

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: Bidistilled water
Details on oral exposure:
Method of administration:
Gavage
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 10 animals at 0 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 200 mg/kg bw/day
Male: 10 animals at 1000 mg/kg bw/day
Female: 10 animals at 0 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 200 mg/kg bw/day
Female: 10 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
MORTALITY:

No deaths occurred during the test.


CLINICAL SIGNS:

No clinical signs of toxicity were observed. As passive

effects of the test substance, dark feces were noted in
animals of mid- and high dose group and violet discoloration
of the urine and of the limbs were noted in high dose
group.


BODY WEIGHTS:

No changes on body weights noted.


FUNCTIONAL OBSERVATION BATTERY:

No test article-related signs were noted in any animal.


GRIP STRENGTH:

No test article-related signs were noted in any animal (only
an incidental effect as greater mean forelimb strength was
noted in some males at 1000 mg/kg).



LOCOMOTOR ACTIVITY:

No test article-related differences in locomotor activity
were observed in any animal.


FOOD CONSUMPTION:

No changes observed during the whole study.

Laboratory findings:
HEMATOLOGY:

The hematology parameters were considered to be unaffected
by the test article.


CLINICAL BIOCHEMISTRY:

Plasma glucose levels were decreased in all animals treated
with 1000 mg/kg and cholesterol (males and females),
triglyceride and phospholipid levels (males) were elevated
when compared with the control animals.


URINALYSIS:

No changes were noted during the whole study.

Effects in organs:
ORGAN WEIGHTS:

No test article-related changes noted.


MACROSCOPIC FINDINGS:

Discoloration of various organs was observed in both sexes
in the high dose group.


MICROSCOPIC FINDINGS:

The high dose group animals showed the following
treatment-related findings:

heart: increased progressive myocardiopathy in males;

stomach: increased hyperkeratosis of nonglandular stomach,
increased eosinophilic inflammatory infiltration in all
animals of both sexes; cecum erosion in one high-dose male,
inflammation associated with congestion and oedema in one
male and one female; inflammation of colon in one male.

The findings in heart and stomach persisted until the end of
the recovery period.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
200 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Classified as: Not classified
Executive summary:

Classified as: Not classified