1,2,4-Oxadiazole, 3-phenyl-5-(2-thienyl)-

Endpoint summary

Description of key information

The test substance is considered to be of low acute oral and dermal toxicity with LD50 values >5,000 mg/kg bw.

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

Study period:

From August 24, 2011 to September 9, 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD Guideline 425 and OPPTS 870.1100, in compliance with GLP.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories
- Age at study initiation: 9 weeks
- Weight at study initiation: 160-171 grams
- Fasting period before study: Fasted overnight
- Housing: Singly housed in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 or 9 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23°C
- Humidity (%): 57-85%
- Air changes (per h): 15
- Photoperiod (h dark / h light): 12 h light/dark cycle

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30% w/w
- Preliminary solubility testing indicated that mixtures in excess of 30% (i.e., 40 to 80%) were too viscous to be administered properly

Doses:

5,000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Individual body weights of the animals were recorded on Days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: All animals were observed for mortality, signs of gross toxicity, and behavioural changes during the first several hours post-dosing and at least once daily thereafter for 14 d after dosing. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, and coma. All rats were euthanized via CO2 inhalation at the end of the 14 d observation period. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed

Clinical signs:

other: No signs of gross toxicity, adverse pharmacologic effects, or abnormal behaviour were observed.

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute oral LD50 of the test substance was >5,000 mg/kg bw in female rats.

Executive summary:

A study was conducted to assess the acute oral toxicity of the test substance in rats according to OECD Guideline 425 and OPPTS 870.1100. The test substance was administered by gavage to overnight fasted female rats. An initial limit dose of 5,000 mg/kg was administered to one healthy animal. Due to the absence of mortality in this animal, two additional animals received the same dose level, simultaneously. Since these animals survived, no additional animals were tested. All animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 d after dosing. Body weights were recorded prior to test substance administration and then on Day 7 and 14 (termination). Necropsies were performed at terminal sacrifice. All animals survived, gained body weight and appeared active and healthy during the study. There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behaviour. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14 d observation period. Based on the results of the study, the acute oral LD₅₀of the test substance was >5,000 mg/kg bw in female rats (Durando J, 2011a).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

High quality database.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From August 23, 2011 - September 21, 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD Guideline 402 and U. S. EPA OPPTS 870.1200, in compliance with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 295-318 grams (males) and 205-225 grams (females)
- Housing: Singly housed in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 21 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23°C
- Humidity (%): 50-74%
- Air changes (per h): 12 and 14
- Photoperiod (h dark / h light): 12 h light/dark cycle

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- On the day prior to application of test substance, a group of animals was prepared by clipping the dorsal area and the trunk. After clipping and prior to application, the animals were examined for health, weighed (initial), and the skin checked for any abnormalities.
- Area of exposure: 2 inches x 3 inches.
- % coverage: Test substance was then applied evenly over a 2-inch x 3-inch, 4-ply gauze pad and placed on a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface). 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): Test sites were gently cleansed with 3% soap solution and a water rinse.
- Time after start of exposure: 24 h.

TEST MATERIAL
- Ground test substance was moistened with distilled water to achieve a dry paste by preparing a 65% w/w mixture.

Duration of exposure:

24 h

Doses:

5,000 mg/kg bw

No. of animals per sex per dose:

5/sex

Control animals:

not required

Details on study design:

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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed

Clinical signs:

other: All rats exhibited ocular and/or nasal discharge on Day 1 or 2, and three females showed signs of ano-genital staining from Days 1 through 13. Dermal irritation was noted at the dose site and/or mechanical damage due to unwrapping around the dose site for

Gross pathology:

No gross abnormalities were noted for any of the animals.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of the study, the acute dermal LD50 of the test substance was >5,000 mg/kg bw in rats.

Executive summary:

A study was conducted to assess the acute dermal toxicity of the test substance to rats according to OECD Guideline 402 and OPPTS 870.1200. 5,000 mg/kg bw of the test substance were moistened with distilled water and then applied to the approximately 2 inches x 3 inches skin of ten healthy rats for 24 h (approximately 10% of the body surface). The animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 d. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed at terminal sacrifice. No mortality was observed. Following patch removal, all rats exhibited ocular and/or nasal discharge on Day 1 or 2, and three females showed signs of ano-genital staining from Day 1 through 13. Dermal irritation was noted at the dose site and/or mechanical damage due to unwrapping around the dose site for four of five males on Day 1. Although three females lost body weight through Day 7, all animals gained weight over the entire observation period. No gross abnormalities were noted when necropsied at the conclusion of the 14 d observations period. Based on the results, the acute dermal LD₅₀of the test substance was >5,000 mg/kg bw in rats (Durando J, 2011b).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

High quality database.

Additional information

Oral

A study was conducted to assess the acute oral toxicity of the test substance in rats according to OECD Guideline 425 and OPPTS 870.1100. The test substance was administered by gavage to overnight fasted female rats. An initial limit dose of 5,000 mg/kg was administered to one healthy animal. Due to the absence of mortality in this animal, two additional animals received the same dose level, simultaneously. Since these animals survived, no additional animals were tested. All animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 d after dosing. Body weights were recorded prior to test substance administration and then on Day 7 and 14 (termination). Necropsies were performed at terminal sacrifice. All animals survived, gained body weight and appeared active and healthy during the study. There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behaviour. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14 d observation period. Based on the results of the study, the acute oral LD₅₀ of the test substance was >5,000 mg/kg bw in female rats (Durando J, 2011a).

Dermal

A study was conducted to assess the acute dermal toxicity of the test substance to rats according to OECD Guideline 402 and OPPTS 870.1200. 5,000 mg/kg bw of the test substance were moistened with distilled water and then applied to the approximately 2 inches x 3 inches skin of ten healthy rats for 24 h (approximately 10% of the body surface). The animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 d. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed at terminal sacrifice. No mortality was observed. Following patch removal, all rats exhibited ocular and/or nasal discharge on Day 1 or 2, and three females showed signs of ano-genital staining from Day 1 through 13. Dermal irritation was noted at the dose site and/or mechanical damage due to unwrapping around the dose site for four of five males on Day 1. Although three females lost body weight through Day 7, all animals gained weight over the entire observation period. No gross abnormalities were noted when necropsied at the conclusion of the 14 d observations period. Based on the results, the acute dermal LD₅₀ of the test substance was >5,000 mg/kg bw in rats (Durando J, 2011b).

Justification for selection of acute toxicity – oral endpoint
The study followed internationally accepted guidelines and conducted in compliance with GLP.

Justification for selection of acute toxicity – dermal endpoint
The study followed internationally accepted guidelines and conducted in compliance with GLP.

Justification for classification or non-classification

Oral route:

Based on the results of an acute oral toxicity study, the test substance does not need to be classified for this endpoint according to the CLP criteria (EC 1272/2008) as well as Directive 67/548/EEC.

Dermal route:

Based on the results of an acute dermal toxicity study, the test substance does not need to be classified for this endpoint according to the CLP criteria (EC 1272/2008) as well as Directive 67/548/EEC.