2-amino-4,6-dinitrophenol

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Data source

Reference

Reference Type:

secondary source

Title:

OPINION ON Picramic acid and sodium picramate COLIPA n° B28

Author:

Scientific Committee on Consumer Safety

Year:

2012

Bibliographic source:

Scientific Committee on Consumer Safety, (SCCS) 18 September 2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-amino-4,6-dinitrophenol

EC Number:

202-544-6

EC Name:

2-amino-4,6-dinitrophenol

Cas Number:

96-91-3

Molecular formula:

C6H5N3O5

IUPAC Name:

2-amino-4,6-dinitrophenol

Test material form:

other: Dark red needles

Details on test material:

- Name of test material (as cited in study report): picramic acid
- Molecular formula (if other than submission substance): C6H5N3O5
- Molecular weight (if other than submission substance): 199.12 g/mol
- Substance type: Organic
- Physical state: solid
- Purity: 100% pure

Test animals

Species:

rat

Strain:

other: Wistar derived SPF-Albino Crl:Wi/Br

Details on test animals or test system and environmental conditions:

Sex: Female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% sodium carboxymethylcellulose

Details on exposure:

VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: 0, 10, 30 and 60 mg/kg bw/day.
- Amount of vehicle (if gavage): 10 ml/kg bw

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

No data available

Duration of treatment / exposure:

During day 5 to day 15 of gestation

Frequency of treatment:

Daily

Duration of test:

10 days

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 10, 30 and 60 mg/kg bw/day
Basis:
no data

No. of animals per sex per dose:

Total no of animals-80
0 mg/kg bw/day- 20 female rats
10 mg/kg bw/day - 20 female rats
30 mg/kg bw/day- 20 female rats
60 mg/kg bw/day - 20 female rats

Control animals:

yes

Examinations

Maternal examinations:

The mortality, signs of intoxication, body weight and food consumption were recorded.

Ovaries and uterine content:

For each ovary, corpora lutea were counted.

Fetal examinations:

Foetuses were individually weighed and sexed.

Statistics:

Yes ,appropriate data is not available.

Indices:

Yes ,appropriate data is not available.

Historical control data:

No data available.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
No mortality was observed during the treatment period. No toxic effects were reported during the study. Females of all dose groups had orange-brown discolored urine throughout the application period at dose related intensity. Mean maternal bodyweight gains and mean food consumptions over the gestation period were normal when compared to the control group. Gross necropsy did not reveal any organ alterations related to treatment. No significant differences in the number of viable fetuses, the male to female sex ratio, birth- position, number of runts, post-implantation losses, implantations, resorptions and corpora lutea between dosage groups and the control group were observed. The highest dose (60 mg/kg/day) group showed an increase in fetal body weight and uteri weights with a tendency towards dose-relation.

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Examination of the fetuses yielded minor variations (wavy ribs) at comparable inter-group frequencies and incidences within the historical control animals of this strain. There were no biologically significant differences in the number of litters with malformations or developmental variations between any of the dose groups and the control group.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

30 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL was found to be 30 mg/kg/day for Picramic acid in male and female Wistar derived SPF-Albino Crl:Wi/Br rats where there dams were exposed at concentration 0, 10, 30 and 60 mg/kg bw/day during gestation period of 5-15 days by oral gavage.

Executive summary:

In devlopmental study of Picramic acid was assessed in male and female Wistar derived SPF-Albino Crl:Wi/Br rats where there dams were exposed at concentration 0, 10, 30 and 60 mg/kg bw/day during gestation period of 5-15 days.

At 60mg/kg/day dose group, there was an increase in foetal body weight and uterine weights and it was dose related change. No significant chage was observed at 30 mg/kg/day.

Therefore the No Observed Adverse Effect Level (NOAEL) of picramic acid in female rats after daily oral treatment is determined to be 30 mg/kg bw/day for the maternal and foetal organisms.