2-methyl-1-(4-methylthiophenyl)-2-morpholinopropan-1-one

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test compliant with GLP and Guideline OECD 408

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Year:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methyl-1-(4-methylthiophenyl)-2-morpholinopropan-1-one

EC Number:

400-600-6

EC Name:

2-methyl-1-(4-methylthiophenyl)-2-morpholinopropan-1-one

Cas Number:

71868-10-5

Molecular formula:

C15H21NO2S

IUPAC Name:

2-methyl-1-(4-methylthiophenyl)-2-morpholinopropan-1-one

Test animals

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: 0.5% carboxymethylcellulose 0.1% Tween 80 in distilled water

Details on oral exposure:

Method of administration:gavage

Duration of treatment / exposure:

Test duration: 90 days

Frequency of treatment:

Dosing regime: 5 days/week

No. of animals per sex per dose:

Male: 10 animals at 10 mg/kg bw/day
Male: 10 animals at 25 mg/kg bw/day
Male: 10 animals at 75 mg/kg bw/day
Male: 10 animals at 220 mg/kg bw/day
Female: 10 animals at 10 mg/kg bw/day
Female: 10 animals at 25 mg/kg bw/day
Female: 10 animals at 75 mg/kg bw/day
Female: 10 animals at 220 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
Mortality:
No treatment related mortality occurred.
Signs of systemic toxicity:
In animals treated with 220 mg/kg bw paresis of the hind limbs and loss of hair was observed. The effects on locomotor activity became less at the end of the study.
Starting the second week of treatment dim and opaque eyes at the highest dose level were noted.
Laboratory findings:
Hematology and blood chemistry:
The number of segmented neutrophiles and plateles were increased in females at 75 mg/kg bw and 220 mg/kg bw. Small effects on liver-derived enzymes were observed in the highes dose group.
Effects in organs:
Eye cataract formation and segmental demyelination of peripheral nerve fibres was noted. In some animals spleen hemosiderosis was observed.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

75 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day

2

Dose descriptor:

NOEL

Effect level:

10 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day

Target system / organ toxicity

Critical effects observed:

not specified