2-amino-6-methyl-4-propyl-1,2,4-triazolo[1,5-a]pyrimidin-5(4H)-one

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1970

Report date:

1970

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Twenty pregnant rats per dose were dosed with 0, 0.25, and 1.25 mg/kg bw test substance on day 6 - 15 of the pregnancy by oral gavage.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-amino-6-methyl-4-propyl-1,2,4-triazolo[1,5-a]pyrimidin-5(4H)-one

EC Number:

248-383-5

EC Name:

2-amino-6-methyl-4-propyl-1,2,4-triazolo[1,5-a]pyrimidin-5(4H)-one

Cas Number:

27277-00-5

Molecular formula:

C9H13N5O

IUPAC Name:

2-amino-6-methyl-4-propyl-1,2,4-triazolo[1,5-a]pyrimidin-5(4H)-one

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

other: albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: between 100 and 144 g
- Housing: 5 to a cage
- Diet: standard pelleted diet, ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: nonylphenolethyleneoxide 0.1%, sodium salt of sulphated cetyl/oleyl alcohol mixture 0.1%, polyglyceryl ricinoleate 0.1 %, and water to 100 %

Details on exposure:

VEHICLE
The suspensions of 0.1 % (w/v), 0.025 % (w/v), and 0.005% (w/v) were prepared by ball milling the drug into a solution of nonylphenolethyleneoxide 0.1 %, sodium salt of sulphated cetyl/oleyl alcohol mixture 0.1 %, polyglyceryl ricinoleate 0.1 %, and water to 100 % .

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

days 6 - 15 of pregnancy

Frequency of treatment:

daily

Duration of test:

Until one day before parturition or after the weaning period.

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.25, and 1.25 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

20

Control animals:

yes, concurrent vehicle

Examinations

Maternal examinations:

Body weight was monitored

Ovaries and uterine content:

The foetuses removed from the uteri one day before parturition were dissected and closely inspected for soft tissue changes and then submitted for alizarin examination.

Fetal examinations:

Offspring that died before weaning were dissected and then sent for alizarin examination. The young that survived to wean were then killed and examined for soft tissue changes.

Indices:

Stillbirths and resorption rates were observed.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Female rats dosed with 1.25 mg/kg bw test substance failed to gain as much weight as the controls. This was probably due to an anorexic effect.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Maternal abnormalities

Abnormalities:

no effects observed

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Dosing the mothers during pregnancy with the test substance had no significant effect on stillbirths or resorption rates. Also litter size and mean weights of the offspring were not statistically different from control values. Alizarin and tissue examinations showed no gross abnormalities due to the test substance dosing and all changes were within the normal limits for this strain of rat. Two foetuses in the control group exhibited mild wrist flexure and one had scoliosis. In the 0.25 mg/kg bw dose group, one offspring had a compressed rib cage. Apart from hydronephrosis no other abnormalities were detected.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: developmental toxicity

Fetal abnormalities

Abnormalities:

no effects observed

Overall developmental toxicity

Developmental effects observed:

no

Applicant's summary and conclusion

Conclusions:

Under the conditions of the test no teratogenic effects were observed.

Executive summary:

Twenty pregnant rats per dose were dosed with 0, 0.25, and 1.25 mg/kg test substance on day 6 - 15 of the pregnancy by oral gavage. At 1.25 mg/kg signs of maternal toxicity were observed i.e. lack of appetite and poor maternal weight gain. Under the conditions of the test no teratogenic effects were observed.