2-amino-4,6-dinitrophenol

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: no data

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:

other:

Principles of method if other than guideline:

Evaluation on the Reprotoxicity of Picramic acid in rats

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

Sex:

female

Details on test animals or test system and environmental conditions:

No data available.

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
- Lot/batch no. (if required):
- Purity

Details on mating procedure:

No data available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

During day 5 to day 15 of gestation

Frequency of treatment:

Daily

Details on study schedule:

80 pregnant rats of the Wistar strain were treated once daily by oral gavage of picramic acid in 0.5% sodium carboxymethylcellulose during day 5 to day 15 of gestation atdoses of 0, 10, 30 and 60 mg/kg bw/d. The animals received a constant volume of 10 ml/kg bw/d. The test procedure followed the OECD guideline and was conducted in compliance with the principles of GLP.During the study the mortality, signs of intoxication, body weight and food consumption were recorded. All mated females were sacrified on day 20 of gestation. In the pregnant female, a complete autopsy and a macroscopic examination of the organs were carried out. Uterus were weighed and examined. For each ovary, corpora lutea were counted and foetuses were individually weighed and sexed. A gross examination of all foetuses was performed and one-third of the foetuses were examined for visceral anomalies. The other foetuses were evaluated for skeletal defects.

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, concurrent vehicle

Examinations

Parental animals: Observations and examinations:

The mortality, signs of intoxication, body weight and food consumption were recorded. For each ovary, corpora lutea were counted.

Oestrous cyclicity (parental animals):

No data available.

Sperm parameters (parental animals):

No data available.

Litter observations:

Foetuses were individually weighed and sexed.

Postmortem examinations (parental animals):

All mated females were scarified on day 20 of gestation. In the pregnant female, a complete autopsy and a macroscopic examination of the organs were carried out. Uterus were weighed and examined

Postmortem examinations (offspring):

A gross examination of all foetuses was performed and one-third of the foetuses were examined for visceral anomalies. The other foetuses were evaluated for skeletal defects

Reproductive indices:

No data available.

Offspring viability indices:

Yes, appropriate data is not available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Description (incidence and severity):

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.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Mean maternal bodyweight gains and mean food consumptions over the gestation period were normal when compared to the control group

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Mean maternal bodyweight gains and mean food consumptions over the gestation period were normal when compared to the control group

Organ weight findings including organ / body weight ratios:

no effects observed

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

30 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No significant effect were observed in foetal body weight and uteri weights

Results: F1 generation

Details on results (F1)

No significant differences in the number of viable foetuses, 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 group showed an increase in foetal body weight and uteri weights with a tendency towards dose-relation. Examination of the foetuses 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

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL was found to be 30 mg/kg/day for Picramic acid in female Wistar derived SPF-Albino Crl:Wi/Br rats when they 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 a reprotox study of Picramic acid was assessed in female Wistar derived SPF-Albino Crl:Wi/Br rats when they were exposed at concentration0, 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 toxicity.