1H-1,2,4-triazole, sodium salt

Endpoint summary

Description of key information

LD0 (oral) >1000 mg/kg bw (Dufour 1992 (1), OECD guideline study ).
LD50 (oral) <2000 mg/kg bw (Dufour 1992 (2), OECD guideline study ).
LD0 (dermal) > 2000 mg/kg bw (Ollivier 2003, OECD guideline and GLP study).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From Aug. 18, 1992 to Sep. 24, 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 401/423). No GLP study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

year of guideline not reported

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

reliability scoring based on 2001

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

no

Route of administration:

oral: gavage

Vehicle:

other: 0.5% (w/v) methylcellulose in water

Details on oral exposure:

no

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

no

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

< 2 000 mg/kg bw

Mortality:

9 rats in 10 died in less than 24 hours. 3 animals (2 males, 1 female) died between 6 and 7 hours after the start of the test. The following day, 6 rats (3 males, 3 females) were found dead. The only one surviving animal (female) was in a coma. No amelioration of its state was observed during the following 48 hours. The last one, moribund was sacrificed 3 days after the treatment.

Clinical signs:

other: One hour after the treatment, the spontaneous motor activity of all animals decreased. Some showed symptoms of respiratory difficulties (gasping). A few rats showed symptoms like piloerection and hollow side. The first severe signs of toxicity were observ

Gross pathology:

The necropsy carried out on all animals revealed stomach (meteorism, glandular mucosa diffusely red) and intestinal (small intestine distended and inflamed) changes.

Other findings:

no

Conclusions:

Under the experimental conditions adopted, the oral LD50 of the substance 1,2,4-TRIAZOLE SODIUM SALT in male and female rats is smaller than 2000 mg/kg.

Executive summary:

Groups of 5 rats/sexe were exposed to 1,2,4 -triazole sodium salt by gavage at 2000 mg/kg bw, according to the OECD guideline. 1,2,4 -triazole sodium salt was dilued in 0.5%(w/v) methylcellulose in water. 9 rats in 10 died in less than 24 hours. Under the experimental conditions adopted, the oral LD50 of 1,2,4 -triazole sodium salt in male and female rats is smaller than 2000 mg/kg.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From Sep. 1, 1992 to Sep. 24, 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 401/420). No GLP study.

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

year of guideline not reported

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: IFFA CREDO (69210-L'ARBRESLE, FRANCE)
- Age at study initiation: 6 weeks
- Weight at study initiation: males: 201 to 215 g; females: 177 to 191 g
- Fasting period before study: overnight
- Housing: 5 animals/sex in polypropylene cages
- Diet (e.g. ad libitum): complete pelleted rat maintenance diet A04 UAR (91360-EPINAY SUR ORGE, FRANCE)
- Water (e.g. ad libitum): not reported
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
Housing conditions in accordance with the requirements of the 86/609/EEC guideline
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Route of administration:

oral: gavage

Vehicle:

other: methylcellulose 0.5% (w/v) in water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.5% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg

Doses:

1000 mg/kg

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily. The continuous observations during the six hours following the ingestion are renewed each following day. Body weight taken before fasting, prior to dosing, and at days 3, 7, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights
Interpretation of the results was done according to European Commission Directive 67/548/EEC

Statistics:

no

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 1 000 mg/kg bw

Mortality:

none

Clinical signs:

other: No specific changes related to treatment were found one hour after the gavage. The first signs of toxicity appeared one hour later. They increased during the following 5 hours. The main symptoms observed were: piloerection, dyspnea, sedation, hyptonia, ab

Gross pathology:

The post-mortem examination of the animals 14 days after the treatment does not show any visible organic or tissular lesions.

Other findings:

no

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

In this study, the LD0 exceeds the administered dose of 1000 mg/kg body weight.

Executive summary:

Groups of 5 rats/sexe were exposed to 1,2,4 -triazole sodium salt by gavage at 1000 mg/kg bw, according to the OECD guideline. 1,2,4 -triazole sodium salt was dilued in 0.5%(w/v) methylcellulose in water. Rats were observed during 14 days after administration.

No deaths occured (0% mortality) during the study. No specific changes related to treatment were found one hour after the gavage. The first signs of toxicity appeared one hour later and increased during the following 5 hours (piloerection, dyspnea, sedation, hyptonia, abnormal gait). In this study, the LD0 exceeds the administered dose of 1000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 1 000 - < 2 000 mg/kg bw

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 Oct. 7, 2003 to Dec. 17, 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study (OECD 402)

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

other: limit test

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: 8 weeks old
- Weight at study initiation: 293 ± 8 g for males and 240 ± 3 g for females
- Housing:During the acclimation period, one to seven animals of the same sex were housed in polycarbonate cages with stainless steel lid. During the treatment period, the animals were housed individually in polycarbonate cages with stainless steel lid. Each cage contained autoclaved sawdust (SICSA, Alfortville, France).
- Diet (e.g. ad libitum): free access to A04 C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France)
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: October 7, 2003 To: October 21, 2003

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal area
- % coverage: 10%
- Type of wrap if used: adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test item was removed using a moistened cotton pad.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg

Duration of exposure:

24 hours

Doses:

Single dose of 2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: Observations were made at least once daily until day 15
- Frequency of observations and weighing:The animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until day 15. The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Mortality:

No deaths occured during the study (0% mortality).

Clinical signs:

other: No clinical signs were observed during the study. Crusts were noted in 4/5 females and 1/5 males between day 2 and the end of the observation period (day 15). Dryness of the skin was also recorded in 2/5 females from day 11 up to day 14.

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Other findings:

no

Interpretation of results:

GHS criteria not met

Conclusions:

Under experimental conditions, the dermal LD0 of the test item 1, 2, 4-TRIAZOLE, SODIUM SALT is equal to or higher than 2000 mg/kg in rats.
According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), the test item does not present a significant acute toxic risk in contact with skin.

Executive summary:

Groups of 5 male and female rats were exposed to 1, 2, 4-TRIAZOLE, SODIUM SALT at 2000 mg/kg bw by dermal route (semiocclusive) during 24 hours. Observations were made at least once daily until day 15. No deaths occured during the study (0% mortality), and no clinical signs were observed during the study.

Under experimental conditions, the dermal LD0 of the test item 1, 2, 4-TRIAZOLE, SODIUM SALT is equal to or higher than 2000 mg/kg in rats.According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), the test item does not present a significant acute toxic risk in contact with skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

> 2 000 mg/kg bw

Additional information

Acute toxicity oral :

Two guideline studies was available for this endpoint. In these studies, groups of 5 male and 5 female rats were exposed to 1000 or 2000 mg/kg bw 1,2,4-Triazole sodium salt by gavage. Animals were observed during 14 days after the administration.

In the first study (Dufour 1992 (1)), rats were exposed to 1000 mg/kg bw, and no deaths occured (0% mortality). No specific changes related to treatment were found one hour after the gavage. The first signs of toxicity appeared one hour later and increased during the following 5 hours (piloerection, dyspnea, sedation, hyptonia, abnormal gait). According this study, the LD50 exceeds the administered dose of 1000 mg/kg body weight.

In the second study (Dufour 1992 (2)), rats were exposed to 2000 mg/kg bw, and 9 rats in 10 died in less than 24 hours. The first severe signs of toxicity were observed in the 10 animals between the 1h30 and 2 hours after the administration of the test article. There were strong piloerection, dyspnea, signs of pain (hollow side, sudden starts), absence of response to external stimuli such as noise, prostration, coma.Under the experimental conditions adopted, the oral LD50 of 1,2,4-Triazole sodium salt is smaller than 2000 mg/kg.

To sum up of these two studies, the oral LD50 was between 1000 and 2000 mg/kg bw.

Acute toxicity dermal :

One OECD 402 guideline study (Ollivier 2003) was available for this endpoint. Groups of 5 male and female rats were exposed to

1,2,4-Triazole sodium salt at 2000 mg/kg bw by dermal route (semiocclusive) during 24 hours. Observations were made at least once daily until day 15. No deaths occured during the study (0% mortality), and no clinical signs were observed during the study.

Under experimental conditions, the dermal LD0 of the test item 1,2,4-Triazole sodium salt is equal to or higher than 2000 mg/kg in rats.

Acute toxicity inhalation : No available data.

Justification for classification or non-classification

According to EU regulation (EC) No 1272/2008 (CLP) :

Acute Toxicity Oral : 1,2,4-Triazole sodium salt was classified in the category 4 "Warning" (1000< LD50 < 2000 mg/kg bw).

Acute Toxicity Dermal : 1,2,4-Triazole sodium salt was not classified (LD0>2000 mg/kg bw)