Sodium 4(or 5)-methyl-1H-benzotriazolide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well performed and documented study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 4(or 5)-methyl-1H-benzotriazolide

EC Number:

265-004-9

EC Name:

Sodium 4(or 5)-methyl-1H-benzotriazolide

Cas Number:

64665-57-2

Molecular formula:

C7H7N3.Na

IUPAC Name:

sodium 4(or5)-methylbenzotriazol-1-ate

Test material form:

other: solution

Details on test material:

- Name of test material (as cited in study report): Preventol CI 7-50
- Substance type: organic
- Physical state: solution
- Composition of test material, percentage of components: 50 % aqueous solution
- Lot/batch No.: 150-5-45
- Storage condition of test material: tightly closed container

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sasco, Inc., Omaha, Nebraska
- Weight at study initiation: 229 to 391 g (male), 232 to 289 g (female)
- Fasting period before study: yes
- Housing: stainless steel cages, 5 animals per cage
- Diet: Purina laboratory rodent checkers
- Water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 23.5
- Humidity (%): 35 - 55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 362 - 1080 mg/kg bw
- Amount of vehicle (if gavage): 1 % of body weight

Doses:

female: 362/434/521/625/685/750/822/900/1080 mg/kg
male: 362/434/521/625/750/822/900/1080 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
observation: yes, nofrequency mentioned
weighing: on the day of treatment, on day 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

LD50 values were calculated by probit analysis using software from SAS Institute, Inc., Cary, North Carolina. Mortality data at each dose level was utilized in the calculation of the LD50 value and confidence interval.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

735 mg/kg bw

Based on:

test mat.

95% CL:

> 660 - < 832

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

930 mg/kg bw

Based on:

test mat.

95% CL:

> 831 - < 1 114

Mortality:

Mortality occurred in female rats at doses of 685 mg/kg or higher and in male rats at doses of 822 mg/kg or higher. The time of death was within 7 hours after application, only in the female group treated with 822 mg/kg bw death occured 23 hours after application

Clinical signs:

other: Clinical signs occurred in both sex at doses of 362 mg/kg or higher. Signs progressed from decreased physical activity at lower doses to ataxia at higher doses with lacrimation being observed prior to death. Additional signs observed in surviving animals,

Gross pathology:

Gross lesions observed in female animals found dead within the first 24 hours postadministration included:
white to tan nasal discharge, fluid-filled gastrointestinal tract, salivation, dark red or mottled lungs.
Incidental findings in female animals included:
ocular abnormality, dilated right renal pelvis and cannibalism.
Gross lesions observed in male animals found dead within the first 24 hours postadministration included:
fluid in the gastointestinal tract.
Incidental findings in male animals included:
dark red lungs, hyperemia of the gastric mucosa.

The surviving animals showed after 14 days no copound-related lesions.

Applicant's summary and conclusion

Conclusions:

The study is well performed and gives following results for the Endpoint:
The LD50 for the acute oral toxicity is 735 mg/kg bw (for female animals, for males a higher value and therefore less concerning value is found).
The NOEL is less than 362 mg/kg.