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Toxicological information

Developmental toxicity / teratogenicity

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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

1
Chemical structure
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 / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
vehicle control, group K
Dose / conc.:
15 mg/kg bw/day (nominal)
Remarks:
group A
Dose / conc.:
45 mg/kg bw/day (nominal)
Remarks:
group B
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.

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