2-aminopyridin-3-ol

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14.06. - 06.07.1993

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

yes

Test material

Test material information

1

Reference substance name:

2-aminopyridin-3-ol

EC Number:

240-886-8

EC Name:

2-aminopyridin-3-ol

Cas Number:

16867-03-1

Molecular formula:

C5H6N2O

IUPAC Name:

2-aminopyridin-3-ol

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

Number of animals: 55 males, 55 females.
Age: approx. 10 weeks (females), older than 12 weeks (males).
Acclimatisation period: 11 days.
Animal identification: tattoo in the right pinna (females), labeling on the tail with felt tip pen (males).

Conditions:
Room temperature: approx. 22 °C
Relative humidity: approx. 55 %
Air exchange: 12 / h.
Light: artificial light from 6 a.m. to 6 p.m.
Bedding material: Aspen woord chips
Food: Ad libitum
Water: Ad libitum, deionisied water

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Duration of treatment / exposure:

day 6 throughout day 15 of gestation, dose volume: 10 mL/kg bw

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Remarks:

vehicle control, group K

Doses / concentrations 2

Dose / conc.:

15 mg/kg bw/day (nominal)

Remarks:

group A

Doses / concentrations 3

Dose / conc.:

45 mg/kg bw/day (nominal)

Remarks:

group B

Doses / concentrations 4

Dose / conc.:

135 mg/kg bw/day (nominal)

Remarks:

group C; Dosage was 135 mg/kg body weight in the beginning of the
study and was lowered to 90 mg/kg body weight after 5 days dosing as mortality occurred.

No. of animals per sex per dose:

25 (females)

Control animals:

yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Key result

Dose descriptor:

NOAEL

Effect level:

45 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

behaviour (functional findings)

body weight and weight gain

changes in number of pregnant

changes in pregnancy duration

clinical biochemistry

clinical signs

dead fetuses

early or late resorptions

effects on pregnancy duration

food consumption and compound intake

gross pathology

haematology

histopathology: neoplastic

maternal abnormalities

mortality

necropsy findings

number of abortions

ophthalmological examination

organ weights and organ / body weight ratios

pre and post implantation loss

total litter losses by resorption

urinalysis

water consumption and compound intake

Results (fetuses)

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEL

Effect level:

45 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

reduction in number of live offspring

changes in sex ratio

fetal/pup body weight changes

changes in litter size and weights

changes in postnatal survival

external malformations

skeletal malformations

visceral malformations

Overall developmental toxicity

Key result

Developmental effects observed:

yes

Lowest effective dose / conc.:

90 mg/kg bw/day (nominal)

Treatment related:

yes

Relation to maternal toxicity:

developmental effects as a secondary non-specific consequence of maternal toxicity effects

Dose response relationship:

yes

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

It is concluded that none of the effects observed indicate a direct embryotoxic or teratogenic induction to the foetus.
The "no adverse effect level" is 45 mg "A-132"/kg
body weight for the dams and foetuses.

Executive summary:

This study was performed to·reveal possible maternal, embryotoxic and/or Leratogenic effects of the test substance after oral administration.

A toxic effect of the test substance to the dams of the highest dosed group, expressed by mortality and statistically significant decreased body weight gain with corresponding decreased food consumption at the beginning of the dosing period was noted

At skeletal examination of the foetuses statistically significant more foetuses with rudimentary lumbar ribs and variations in general were observed in the highest dose group and this was considered tobe due to maternal toxicity.

The occurrence of statistically significant more foetuses with uncompletely ossified caudal vertebrae of animals of group B and of statistically significant more foetuses with uncompletely ossified pelvis of animals of groups A and B is considered of no relevance as it is not dose dependent.

At visceral examination the occurrence of significant more foetuses with slightly enlarged brain ventricles of groups A and B was also considered of no relevance as it was not dose dependent.

Therefore it is concluded that none of the effects observed indicate a direct embryotoxic or teratogenic induction to the foetus.

The "no adverse effect level" is 45 mg "A-132"/kg body weight for the dams and foetuses.