[1,2,4]Triazolo[1,5-a]pyrimidin-2-amine, 5,7-dimethoxy-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 10 - 24, 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5,7-dimethoxy-[1,2,4]triazolo[1,5-a]pyrimidin-2-amine

EC Number:

603-562-0

Cas Number:

13223-43-3

Molecular formula:

C7H9N5O2

IUPAC Name:

5,7-dimethoxy-[1,2,4]triazolo[1,5-a]pyrimidin-2-amine

Details on test material:

- Name of test material (as cited in study report): ADTP
- Physical state: off-white solid
- Analytical purity: 99.8%
- Lot/batch No.: 041206-5D
- Expiration date of the lot/batch: n/a
- Stability under test conditions: Test substance was expected to be stable for the duration of testing.
- Storage condition of test material: room temperature
- pH: 7-8 (by wetted pH paper)

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Received from Charles River Laboratories, Raleigh, NC on December 28, 2004.
- Age at study initiation: Young adult (9-10 weeks)
- Weight at study initiation: males 198-212 grams and females 126-132 grams at experimental start.
- Fasting period before study: no
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Certified Rodent Diet (PMI #5002)
- Water (e.g. ad libitum): Filtered tap water was supplied ad-libitum by an automatic water dispensing system.
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22°C
- Humidity (%): 30-67% RH
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Type of coverage:

semiocclusive

Details on dermal exposure:

TEST SITE
- Area of exposure: 2-inch x 3-inch
- % coverage: approximately 10% of the body surface
- Type of wrap if used: A 4-ply gauze pad was placed on a dose area. The gauze pad and entire trunk of each animal were then wrapped with 3-inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The pads were removed and the test sites were cleansed of residual test substance.
- Time after start of exposure: After 24 hours of exposure to the test substance

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Five thousand mg/kg of body weight of the test substance was applied.
- Concentration (if solution): Prior to application, the test substance was moistened with distilled water to achieve a dry paste by preparing a 60% w/w mixture.
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): In order to ensure adequate contact with the skin, the sample was applied as a dry paste (60% w/w mixture in distilled water). Preliminary solubility testing indicated mixtures in excess of 60% (i.e., 70%-90%) were too dry to ensure adequate skin contact.

Duration of exposure:

24 hours

Doses:

5000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for mortality, signs of gross toxicity, and behavioral changes for several hours after application and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.
Individual body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination).
- Necropsy of survivors performed: yes
- Other examinations performed: All rats were euthanized via CO2 inhalation on Day 14. Gross necropsies were performed on all animals. The external surface of the body and all orifices, tissues, and organs of the thoracic and abdominal cavities were examined.

Statistics:

no data

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived exposure to the test substance.

Clinical signs:

other: Apart from reduced fecal volume noted for most animals between Days 1 and 2, there were no other signs of gross toxicity, dermal irritation, adverse clinical signs, or abnormal behavior.

Gross pathology:

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

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the single dose acute dermal LD50 of ADTP was greater than 5,000 mg/kg of body weight in male and female rats.

Executive summary:

An acute dermal toxicity test was conducted in accordance with EPA OPPTS 870.1200 (Acute Dermal Toxicity) with F344 rats to determine the potential for ADTP to produce toxicity from a single topical application. Under the conditions of this study, the single dose acute dermal LD50 of the test substance was greater than 5,000 mg/kg of body weight in male and female rats.

Five thousand milligrams of the test substance per kilogram of body weight was moistened with distilled water and applied to the skin of five male and five female healthy rats for 24 hours. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days. Body weights were recorded prior to application on Day 0, and again on Days 7 and 14 (termination). Necropsies were perfolllled on all animals at sacrifice.

All animals survived exposure to the test substance and gained body weight during the study.

Apart from reduced fecal volume noted for most animals between Days 1 and 2, there were no other signs of gross toxicity, dermal irritation, adverse clinical signs, or abnormal behavior. No gross abnormalities were noted for the animals when necropsied at the conclusion of the 14-day observation period.