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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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
Study period:
November to December 2004
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyl 3-((1-(4-methylamino-3-nitrophenyl)methanoyl)pyridin-2-yl-amino)propionate
EC Number:
454-450-1
EC Name:
Ethyl 3-((1-(4-methylamino-3-nitrophenyl)methanoyl)pyridin-2-yl-amino)propionate
Cas Number:
429659-01-8
Molecular formula:
C18 H20 N4 O5
IUPAC Name:
ethyl 3-{1-[4-(methylamino)-3-nitrophenyl]-N-(pyridin-2-yl)formamido}propanoate
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
other: HSDBrl:WH Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 500 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 500 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day
Control animals:
yes

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, non-treatment-related
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Haematological findings:
no effects observed
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
Yellowish discoloration of the urine in all animals from the first day of application was observed.
Details on results:
Clinical observations:
No treatment related lesions; no relevant changes were
recorded upon necropsy; normal food intake.

Laboratory findings:
In the assessment of haematology values no changes of
toxicological relevance were found. With the exception of
the glucose values the determination of clinical chemical
parameters revealed that all mean and most individual values
were within the expected range.

Effects in organs:
Slightly increased values for the organ weights of liver and
spleen were observed but considered adaptation effects
without any toxicological relevance.

Effect levels

Dose descriptor:
NOAEL
Effect level:
ca. 1 000 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:
no

Applicant's summary and conclusion

Conclusions:
Considerimg the reported data of this toxicity study it can be stated, that the High Dose of 1000 mg/kg BW is the no observed adverse effect dose level (NOAEL) of BIBR 1048 Manamide suspended in Carboxymethylcellulose, CMC, (1% in sterile aqua dest.) after a total of 28 applications by gavage over a period of 28 days.