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Diss Factsheets

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
Report date:
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
Limit test:
no

Test material

Constituent 1
Reference substance name:
-
EC Number:
431-440-5
EC Name:
-
IUPAC Name:
(3-{5-[(E)-2-(3-{4-[(E)-2-{1-[3-(dimethylazaniumyl)propyl]-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl}diazen-1-yl]benzamido}phenyl)diazen-1-yl]-6-hydroxy-4-methyl-2-oxo-1,2-dihydropyridin-1-yl}propyl)dimethylazanium (3-{6-hydroxy-5-[(E)-2-(3-{4-[(E)-2-{2-hydroxy-4-methyl-1-[3-(methylazaniumyl)propyl]-6-oxo-1,6-dihydropyridin-3-yl}diazen-1-yl]benzamido}phenyl)diazen-1-yl]-4-methyl-2-oxo-1,2-dihydropyridin-1-yl}propyl)(methyl)azanium (3-{6-hydroxy-5-[(E)-2-(4-{3-[(E)-2-{2-hydroxy-4-methyl-1-[3-(methylazaniumyl)propyl]-6-oxo-1,6-dihydropyridin-3-yl}diazen-1-yl]benzamido}phenyl)diazen-1-yl]-4-methyl-2-oxo-1,2-dihydropyridin-1-yl}propyl)dimethylazanium hexaacetate

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Bidistilled water
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

Examinations

Observations and examinations performed and frequency:
outside Cage observations
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION: yes
HAEMATOLOGY: Yes
CLINICAL CHEMISTRY: Yes
URINALYSIS: Yes
Organ Weight
NEUROBEHAVIOURAL EXAMINATION: Yes
grip strength / motor activity

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
changes in clinical biochemistra parameters were restricted to animals treated with 1000 mg/kg/day; effects were mor frequently noted in males than females; all effects were reversible at the end of the treatment period;
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
changes restricted to males at all dose levels and in females at dose level 200 mg/kg/d or 1000 mg/kg/d; all effects were reversible at the end of the treatment period;
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS:
At 200 and 1000 mg/kg yellow feces were noted in all males and females until the first week of the recovery period.

Laboratory findings:
HEMATOLOGY
The hematology parameters were unaffected at the end of the study.

CLINICAL BIOCHEMISTRY:
At 1000 mg/kg, lower plasma glucose was noted in both sexes, whereas males showed higher blood urea nitrogen and creatinine levels, higher levels of total cholesterol, triglycerides and phospholipides and higher sodium and chloride levels.

URINALYSIS:
At 200 and 1000 mg/kg, changes as lower urine volumne after 18 hours, higher specific gravity and urine osmolality, higher levels of urinary protein and blood and higher ketone levels were noted in several males and/or females.

Effects in organs:
ORGAN WEIGHTS:
No test article-related differences were seen.

MACROSCOPIC & MICROSCOPIC FINDINGS:
No treatment related morphological findings noted.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
50 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
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