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

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test type (migrated information)

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 414(2001) and OECD 415 (1983)

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:

other: "Combined one generation and prenatal developmental toxicity study in rat", OECD 414 (2001) and 415 (1983)

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:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: 0.5% aqueous carboxymethylcellulose

Details on exposure:

Method of adminstration or exposure: gavage

Frequency of treatment:

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

Details on study schedule:

Number of litters per dose/conc.: 24 at mg/kg or mg/l

No. of animals per sex per dose:

Male: 24 animals at 40 mg/kg or mg/l
Male: 24 animals at 80 mg/kg or mg/l
Male: 24 animals at 120 mg/kg or mg/l
Female: 48 animals at 40 mg/kg or mg/l
Female: 48 animals at 80 mg/kg or mg/l
Female: 48 animals at 120 mg/kg or mg/l

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

Statistically significant decreases in body weight were observed in the high dose males on Day 22 and from Day 36 to Day 99 of the study. A statistically significant decrease in body weight gain was observed in the mid-dose males on Day 43 of the study.
A reduction in body weight gain was noted in all group females allowed to give birth on gestation Day 9. This reduction was statistically significant for the mid-dose group.
Fertility index was, in general, decreased in all treated females with particular emphasis in the high dose group.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

40 mg/kg bw/day

Sex:

male/female

Results: F1 generation

Details on results (F1)

Effects on F1 generation:
Stillbirths or total litter loss were noted the day of parturition or the day after parturition in all high dose females which gave birth. Statistically significant increases in pup loss on Day 1 post-partum, cumulative loss on Days 4 and 14 post-partum were observed in the mid-dose group.
In addition, litter weight was statistically significantly decreased in the mid-dose group on Days 1, 4 and 14 post-partum. Litter size and mean pup weight were also statistically significantly decreased in the mid-dose group on Day 14 post-partum. The survival of pups was drastically decreased in the mid-and high dose groups.
Pre-weaning clinical signs showed marked mortality of the pups in the high dose group.
Statistically significant decreases in terminal body weight were observed in the high dose males and in the high dose females.
Lateral ventricles of the brain enlarged, head with domed shape limbs short or malrotated, cleft palate, anasarca and alteration on the tail were present at necropsy of the decedent pups or pups at weaning.

Effect levels (F1)

Dose descriptor:

LOAEL

Generation:

F1

Effect level:

40 mg/kg bw/day

Sex:

male/female

Overall reproductive toxicity

Reproductive effects observed:

not specified