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

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 2001-January 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study meets the requirements of the OECD Principles of Good Laboratory Practice, Paris, 1992.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

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

Constituent 2

Reference substance name:

3,5-bis[(2,3-dihydroxypropyl)carbamoyl]aniliniumchloride

IUPAC Name:

3,5-bis[(2,3-dihydroxypropyl)carbamoyl]aniliniumchloride

Details on test material:

- Name of test material (as cited in study report): ABA-HCl
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state: Powder
- Analytical purity: ≥98.5
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.: S-31308
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material:
- Other:

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: deionised water

Details on mating procedure:

Males were administered 70 days prior to mating up to 24 hours before necropsy. Females were administered 14 days prior to mating and throughout the study up to 24 hours before necropsy of the offspring at day 21 of lactation

Frequency of treatment:

Dosing regime (males): 7 days/week
Dosing regime (females): 7 days/week

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

90 mg/kg bw/day (nominal)

Remarks:

The dose volume was 10 ml per kg body weight.

Doses / concentrations 2

Dose / conc.:

300 mg/kg bw/day (nominal)

Remarks:

The dose volume was 10 ml per kg body weight.

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Remarks:

The dose volume was 10 ml per kg body weight.

No. of animals per sex per dose:

Male: 24 animals at 0 mg/kg or mg/l
Male: 24 animals at 90 mg/kg or mg/l
Male: 24 animals at 300 mg/kg or mg/l
Male: 24 animals at 1000 mg/kg or mg/l
Female: 24 animals at 0 mg/kg or mg/l
Female: 24 animals at 90 mg/kg or mg/l
Female: 24 animals at 300 mg/kg or mg/l
Female: 24 animals at 1000 mg/kg or mg/l

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

other: no NOAEL identified

Effect level:

> 90 - < 1 000 mg/kg bw/day (actual dose received)

Based on:

other: dissolved

Sex:

male/female

Basis for effect level:

mortality

dermal irritation

body weight and weight gain

Remarks on result:

not determinable due to absence of adverse toxic effects

Results: F1 generation

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 90 - <= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

mortality

dermal irritation

body weight and weight gain

Remarks on result:

not determinable due to absence of adverse toxic effects

Overall reproductive toxicity

Reproductive effects observed:

no

Applicant's summary and conclusion

Conclusions:

It was concluded from this study that administration of ABA-HCl to male and female rats had no adverse effect on the reproductive up to a dose of 1000 mg/kg bodyweight.

Executive summary:

One generation Reproduction Toxicity Study in Rats Mortality No test substance related mortality occurred in this test study Animal observation The general condition of the parental animals was unaffected by treatment. Bodyweights and food consumption There were no significant differences in the body weights and in the food consumption. Reproductive performance Mating performance, fertility, gestation length and parturition were unaffected by treatment. Significant higher post-implantation survival indices in all dosed groups compared to the control group were considered incidentally and not test substance related. Viability of offspring was not affected by treatment. Statistically significant lower live birth and viability indices in the lowest dosed group were considered incidentally and not test substance related. Sex ratio and body weight development of offspring was unaffected by treatment. The incidence of external findings in the pups was low. Anasarca (generalized oedema) and a small fissure of the abdominal wall at the navel was noted in one pup of the lowest dosed group. This malformation was assessed as being of spontaneous origin. Necropsy and hystopahthology No treatment related changes were found.