Purine-2(3H),6(1H)-dione

Endpoint summary

Description of key information

Oral: OECD Guideline 425; rat LD50 >2000 mg/kg. Reliability = 1

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

GLP compliance:

yes

Limit test:

yes

Specific details on test material used for the study:

Purity: 99.9%

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Females: yes; 5 females total; nulliparous and non-pregnant
- Age at study initiation: Young adult (9-10 weeks)
- Weight at study initiation: 194.0- 223.8 grams
- Housing: Animals individually housed in plastic solid bottom polycarbonate cages; enrichment (e.g., toy) placed in each cage; Corncob bedding used and changed at least once per week
- Diet (e.g. ad libitum): ad libitum except during fasting (replaced~3-4 hours after dosing)
- Water (e.g. ad libitum): ad libitum (filtered water)
- Fasting: Prior to each dosing, rats fasted overnight by removing feed from cages; during fasting period, rats examined for health and weighed (initial).
- Acclimation period: 14-21 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 -26°C (Temperature was above upper targeted limit for 6 days during study; excursion was considered minor and had no impact on study).
- Humidity (%): 51-85% (Humidity was above targeted upper limit for 6 days during study; portable dehumidifier used to lower humidity levels during this time; excursion was considered minor and had no impact on study).
- Air changes (per hr): 12
- Photoperiod (hrs dark/hrs light): 12-hour light/dark cycle

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40%; 2000 mg/kg
- Lot/batch no. (if required): PSL Reference Number 210421-3H
- Purity: > 99%,

DOSAGE PREPARATION AND ADMINISTRATION: Administered as 40% w/w mixture in distilled water because preliminary sample preparation assessments conducted by testing facility indicated that mixtures in excess of 40% (i.e., 50-80%) were too viscous to be administered properly; test mixture administered to stomach using stainless steel ball-tipped gavage needle attached to syringe.





:

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 females

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Within 30 minutes post-dosing, during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing.
- Necropsy of survivors performed: Yes
- Clinical signs observed: Gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern; attention directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Statistics:

Statistical analysis was limited to calculation of mean density value for dosing.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived test substance administration.

Clinical signs:

other:

Body weight:

lower than 10% body weight loss

Remarks:

All animals gained weight during the study.

Gross pathology:

No gross abnormalities noted for any animals when necropsied at conclusion of 14-day observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of the test material > 2000 mg/kg of body weight in female rats.

Executive summary:

An acute oral toxicity test was conducted with rats to determine the potential for the test material to produce toxicity from a single dose via the oral route. An initial limit dose of 2000 mg/kg was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, four additional females received the same dose level, sequentially. Since these animals survived, no additional animals were tested. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing. Body weights were recorded prior to administration (initial) and again on Days 7 and 14 (terminal) following dosing. Necropsies were performed on all animals at terminal sacrifice. All animals survived test substance administration, gained body weight, and appeared active and healthy during the study. There were no signs of gross toxicity, adverse clinical effects, or abnormal behavior. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period. Under the conditions of this study, the acute oral LD50 of the test substance is greater than 2000 mg/kg of body weight in female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Guideline, GLP study

Justification for classification or non-classification

Based on the oral rat LD50 of > 2000 mg/kg, the substance does not need to be classified for acute oral toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.