1,3-Benzenedicarboxamide, 5-amino-N1,N3-bis(2,3-dihydroxypropyl)-, hydrochloride (1:1)

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 1996-October 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study described in this report was conducted in compliance with the Good Laboratory Practice (GLP) Regulations

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

421-690-3

EC Name:

-

Cas Number:

203515-86-0

Molecular formula:

C14H21N3O6 . ClH

IUPAC Name:

5-amino-N1,N3-bis(2,3-dihydroxypropyl)benzene-1,3-dicarboxamide hydrochloride

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Distilled water

Duration of treatment / exposure:

Test duration: 90 days

Frequency of treatment:

Dosing regime: 7 days/week

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

2 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

Male: 15 animals at CA 0 mg/kg bw/day
Male: 10 animals at CA 100 mg/kg bw/day
Male: 10 animals at CA 500 mg/kg bw/day
Male: 15 animals at CA 2000 mg/kg bw/day
Female: 15 animals at CA 0 mg/kg bw/day
Female: 10 animals at CA 100 mg/kg bw/day
Female: 10 animals at CA 500 mg/kg bw/day
Female: 15 animals at CA 2000 mg/kg bw/day

Control animals:

yes

Results and discussion

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

2 000 mg/kg bw/day (nominal)

Remarks on result:

other: original NCD unit is mg/kg/day.

2

Dose descriptor:

NOEL

Effect level:

2 000 mg/kg bw/day (nominal)

Remarks on result:

other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

Classified as: Not classified

Male and female CD-Spraque-Dawley rats received daily oral doses by gavage of 0; 100; 500 or 2000 mg ABA-HCl/kg bodyweight for 13 weeks, followed by a 4-week recovery period for the control and top dose group.
Toxicokinetics investigations revealed dose-dependently increased exposured levels. There were no differences of toxicological importance between the treated groups and the control group in mortality, clinical signs, body weight, food consumption, ophthalomology, clinical phatology, macroscopic observations at necropsy, organ weights and histophathology.
Under the present study design, the no-observed-adverse-effect level of ABA-HCl was 2000 mg/kg body weight.

Executive summary:

Treatment with ABA-HCl did not lead to any mortality, clinical signs of toxicity or toxic effects on bodyweight, food consumption, ophthalomology, hematology, blood clotting or clinico-chemical parameters. At the end of the treatment period, statistically significant slight differences in kidney and liver weights were seen in treated groups, but their relation to the treatment was equivocal. No treatment-related effects were observed on macroscopic or histologic organ findings. Toxicokinetics investigations revealed dose-dependently increased exposured levels. Except in male rats receiving 2000 mg/kgbw no major differences in pharmacokinetic parameters obtained were seen when comparing day 1 to day 85 (week 13). While in female rats receiving 2000 mg ABA-HCl/kg bw the pharmacokinetic parameters remained unchanged over the time, in male rats they were increased at day 85 when compared to those obtained at day 1. However, due to high interindividual variations in the plasma concentrations no final conclusion was possible whether or not this increase is biologically significant.