Reaction mass of N-butylphthalimide and N-sec-butylphthalimide and N-propylphthalimide

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-propylphthalimide

EC Number:

226-189-1

EC Name:

N-propylphthalimide

Cas Number:

5323-50-2

Molecular formula:

C11H11NO2

IUPAC Name:

2-propyl-1H-isoindole-1,3(2H)-dione

Constituent 2

Reference substance name:

N-sec-butylphthalimide

EC Number:

233-295-1

EC Name:

N-sec-butylphthalimide

Cas Number:

10108-61-9

Molecular formula:

C12H13NO2

IUPAC Name:

2-sec-butyl-1H-isoindole-1,3(2H)-dione

Constituent 3

Reference substance name:

N-butylphthalimide

EC Number:

216-157-5

EC Name:

N-butylphthalimide

Cas Number:

1515-72-6

Molecular formula:

C12H13NO2

IUPAC Name:

2-butyl-1H-isoindole-1,3(2H)-dione

impurity 1

Reference substance name:

Unknown impurities.

Molecular formula:

Not available as unknown impurities.

IUPAC Name:

Unknown impurities.

1

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

Test material form:

liquid

Details on test material:

Batch CNAA053604
Color: clear yellowish
Form: liquid
Storage conditions: Room temperature in a closed container, protected from light.

Administration / exposure

Route of administration:

oral: gavage

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

50 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

300 mg/kg bw/day (actual dose received)

Results and discussion

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

> 0 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

mortality

Remarks on result:

other: preliminary results, study in progress

Target system / organ toxicity

Key result

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Under the conditions of the present study, Reaction mass of N-butylphthalimide and n-propylphthalimide and N-sec-butylphthalimide administered at 50, 100 or 300 mg/kg bw/day by oral gavage did not cause signs of systemic toxicity and did not adversely influence the reproductive performance (gonad function, mating behavior, conception, parturition) in parental male and female Hsd.Han: Wistar rats.

Executive summary:

Under the conditions of the present study, Reaction mass of N-butylphthalimide and n-propylphthalimide and N-sec-butylphthalimide administered at 50, 100 or 300 mg/kg bw/day by oral gavage did not cause signs of systemic toxicity and did not adversely influence the reproductive performance (gonad function, mating behavior, conception, parturition) in parental male and female Hsd.Han: Wistar rats.

The development of the F1 offspring was not impaired from birth to post-natal day 13 at any dose level after repeated oral administration of dams.

Based on these observations the No Observed Adverse Effect Levels (NOAEL) were determined as follows:

NOAEL for systemic toxicity of male/female rats: 300 mg/kg bw/day

NOAEL for reproductive performance of male/ female rats: 300 mg/kg bw/day

NOAEL for F1 Offspring: 300 mg/kg bw/day