3-Morpholinone, 4-(4-aminophenyl)-

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Study period:

May to Jun 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well reported GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

no special functional observations and motor activity assessment

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-(4-aminophenyl)morpholin-3-one

EC Number:

610-147-8

Cas Number:

438056-69-0

Molecular formula:

C10 H12 N2 O2

IUPAC Name:

4-(4-aminophenyl)morpholin-3-one

Details on test material:

almost white, solid; batch BXR387U; content 100.0% and 99.5%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% awueous Tylose

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 days (males) or 29 days (females)

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.1, 2 and 40 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No toxicologically relevant adverse effects were observed in male and female rats up to and including the highest administered dose of 40 mg/kg.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

One control animal died during blood sampling but no treatment-related mortalities occurred.

No substance-related clinical signs were observed.

Body weight development was neither dose-dependently nor toxicologically relevantly affected in any treated animal group.

Water consumption was not toxicologically relevantly affected in any dose group. Food intake was slightly decreased in males at 40 mg/kg; because body weight was inconspicuous, no adverse effect was assumed.

MCHC slightly increased in males at 2 mg/kg and above and MCH was slightly increased in males at 40 mg/kg whereas MET-HB was slightly decreased in females at 40 mg/kg; without histopathological correlate no adverse effects were considered.

Enzymes, substrates and electrolytes in the peripheral blood were unremarkable.

Necropsy, organ weights and histopathology revealed no treatment-related effects.

Applicant's summary and conclusion

Executive summary:

Anilinomorpholinon was administered orally by gavage to 10 male and female Wistar rats per dose group, in doses of 0, 0.1, 2 and 40 mg/kg body weight for a period of 28 (males)/29 (females) days. The animals were regularly observed and weighed. Food and water intakes were determined. Clinical laboratory investigations of blood samples were performed. Organs and tissues were subjected to gross and histopathological investigation. Selected organs were weighed. No treatment-related adverse effects were observed up to and including the highest dose administered and therefore, the NOAEL for Anilinomorpholinon given orally by gavage was established at 40 mg/kg in male and female rats.