Registration Dossier

Administrative data

Description of key information

Acute oral : LD50 is 1320 mg/kg bw in rat exposed to 1,2,4-triazole (GLP guideline study).
Acute dermal : LD50 is higher to 2000 mg/kg bw in rat exposed to 1,2,4-triazole (GLP guideline (OECD 402) study).
Acute inhalation : No reliable study is available for this endpoint.

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 Sep. 6, 1989 to Dec. 4, 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 401/423)
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987 followed
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
1984 followed
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
reliability scoring based on 2001
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wölferstrasse 4 CH-4414 Füllinsdorf
- Age at study initiation: males 8 to 9 weeks; females 9 to 11 weeks
- Weight at study initiation: males 179 to 235 g; females 159 to 199 g
- Fasting period before study: 12 to 18 hours
- Housing: Groups of 5 in Makrolon type-3 cages with standard bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet (e.g. ad libitum): pelleted standard Kliba 343, Batch 55/89 rat maintenance diet ("Kliba" Klingentalmuehle AG, CH-4303 Kaiseraugst) ad libitum
- Water (e.g. ad libitum): community tap water from Itingen ad libitum
- Acclimation period: one week under laboratory conditions after veterinary examination


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40 to 70
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
other: bi-distilled water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg
Doses:
1000, 1500, and 2000 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: 15 days
- Frequency of observations and weighing: Each animal was examined for changes in appearance and behavior 4 times during day 1 and daily during days 2 to 15. Weighing: Test day 1 (pre-administration), 8, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights
Statistics:
LD50 LOGIT-ESTIMATION
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 320.39 mg/kg bw
95% CL:
> 1 104.09 - < 1 490.9
Mortality:
refer to attached file
Clinical signs:
refer to attached file
Body weight:
The body weight gain of the surviving animals was not affected by the test article treatment throughout the entire study period.
Gross pathology:
refer to attached file
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Harmful if swallowed Criteria used for interpretation of results: other: CLP (EC1272/2008)
Conclusions:
According this study, 1,2,4-triazole is classified in category 4 according to the Regulation EC no.1272/2008 (CLP) with a LD50 of 1320 mg/kg bw.
Executive summary:

A guideline study (OECD 401) was performed in rats to calculate LD50. Rats were exposed to 1,2,4 -triazole at 1000, 1500, and 2000 mg/kg1000, 1500, and 2000 mg/kg bw (a single exposure), and were observed during 15 days. The mortality of each animal was reported and the LD50 was calculated. The LD50 of 1,2,4-triazole is 1320 mg/kg bw in rats.

1,2,4 -triazole is classified in Category 4 according to the regulation EC no.1272/2008 (CLP).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 320 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
1976
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study (OECD 402)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
reliability scoring based on 1987 guideline
Deviations:
yes
Remarks:
Source, purity, chemical characteristics of test substance, temperature, light cycle, and humidity not provided; grading scale not provided
GLP compliance:
no
Remarks:
study pre-dates GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: from the breeder Winkelmann (Borchen)
- Age at study initiation: no data
- Weight at study initiation: 160-180g
- Fasting period before study: no data
- Housing: in tyupe-III Makrolon cages
- Diet (e.g. ad libitum): Altromin R standard diet, ad libitum
- Water (e.g. ad libitum): not precised, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data
Type of coverage:
occlusive
Vehicle:
other: Cremophor EL
Details on dermal exposure:
Test substance was applied to shaven dorsal skin. After 24 hours of application, the skin was washed with water and soap.
Duration of exposure:
24 hours
Doses:
1000, 2000 (females only), 2500, 3500, 4000 (females), 5000 mg/kg body weight
No. of animals per sex per dose:
1000 (5 males; 5 females), 2000 (10 females), 2500 (10 males; 10 females), 3500 (10 males; 10 females), 4000 (10 females), 5000 (10 males; 20 females)
Control animals:
not required
Details on study design:
14 day observation period
Statistics:
The calculation of the mean lethal dose (LD50) in carried out using probit analysis.
Sex:
male
Dose descriptor:
LD50
Effect level:
4 200 mg/kg bw
95% CL:
> 3 081 - < 5 725
Sex:
female
Dose descriptor:
LD50
Effect level:
3 129 mg/kg bw
95% CL:
> 2 203 - < 3 648
Mortality:
Yes
Clinical signs:
The animals exhibited; reduction in general well-being, accompanied by sedation and breathing disorders. At higher doses, the animals were lying in the abdominal or side position. The symptoms appeared within an hour of administration and were observed for a maximum of up to 13 days after administration.
Body weight:
no data
Gross pathology:
Gross pathology examination of the animals revealed no major changes.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (EC1272/2008)
Executive summary:

A guideline study (OECD 402) was performed in rats to calculate LD50 in dermal route. Rats were exposed to 1,2,4 -triazole at 1000, 2000 (females only), 2500, 3500, 4000 (females), 5000 mg/kg body weight (a single exposure), and were observed during 14 days. The mortality of each animal was reported and the LD50 was calculated. The LD50 of 1,2,4-triazole is 4200 mg/kg bw in male rats, and 3129 mg/kg bw in female rats.

1,2,4 -triazole is not classified for acute dermal toxicity according to the regulation EC no.1272/2008 (CLP).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
3 129 mg/kg bw

Additional information

Acute oral :

A guideline study (OECD 401) was performed in rats to calculate LD50. Rats were exposed to 1,2,4 -triazole at 1000, 1500, and 2000 mg/kg1000, 1500, and 2000 mg/kg bw (a single exposure), and were observed during 15 days. The mortality of each animal was reported and the LD50 was calculated. The LD50 of 1,2,4-triazole is 1320 mg/kg bw in rats.

A guideline study (OECD 423) was performed in rats to calculate LD50 (Thyssen, 1976). Rats were exposed to 1,2,4 -triazole 100 (female only), 250, 500, 1000, 1250, 1500, 1750, 1850 (males only), 2000, and 2500 mg/kg body weight (a single exposure), and were observed during 14 days. The mortality of each animal was reported and the LD50 was calculated. The LD50 of 1,2,4-triazole is 1650 mg/kg bw in rats.

A guideline study (OECD 423) was performed in rats to calculate LD50 (Prococio, 1992). The LD50 was estimated between 500 and 5000 mg/kg.

Acute dermal :

A guideline study (OECD 402) was performed in rats to calculate LD50 in dermal route. Rats were exposed to 1,2,4 -triazole at 1000, 2000 (females only), 2500, 3500, 4000 (females), 5000 mg/kg body weight (a single exposure), and were observed during 14 days. The mortality of each animal was reported and the LD50 was calculated. The LD50 of 1,2,4-triazole is 4200 mg/kg bw in male rats, and 3129 mg/kg bw in female rats.

Acute inhalation :

No reliable study is available for this endpoint.

Justification for classification or non-classification

Acute oral :

1,2,4 -triazole is classified in Category 4 (H302: Harmful if swallowed) according to the Regulation EC no.1272/20008 (CLP), and classified "R22 - harmful if swallowed" according to the EU Directive 67/548/EEC.

Justification : LD50 is between 300 and 2000 mg/kg bw (CLP).

Acute dermal :

1,2,4 -triazole is not classified for acute dermal toxicity according to the regulation EC no.1272/2008 (CLP) and according to the EU Directive 67/548/EEC.

Justification : LD50 (males and females) is higher to 2000 mg/kg bw.

Acute inhalation :

1,2,4 -triazole is not classified for acute inhalationl toxicity.

Justification : No reliable study is available for this endpoint.