Sodium 5-N-butylbenzotriazole

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11.08.1988 - 01.09.1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 5-N-butylbenzotriazole

EC Number:

404-450-2

EC Name:

Sodium 5-N-butylbenzotriazole

Cas Number:

118685-34-0

Molecular formula:

CCCCc1ccc2c(c1)nnn2[Na]

IUPAC Name:

sodium 5-butyl-1H-1,2,3-benzotriazol-1-ide

Test material form:

solid - liquid: suspension

Remarks:

37% aqueous solution

Details on test material:

Identification: Butyl benzotriazole-sodium salt (37% solution)
Physical state: Brown liquid
Purity: 37% aqueous solution
Storage: Ambient conditions of humidity and temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Equal numbers of male and female CFY (Sprague-Dawley origin) rats were obtained from Interfauna U.K. Ltd., Huntingdon, Cambridgeshire, England. They were in a weight range of 98 to 150 g prior to dosing (Day 1) in the main study and approximately four to six weeks of age. All the rats Were acclimated to the experimental environment for a period of 8 days prior to the start of the main study.
The rats were allocated to cages within the treatment groups. They were housed in groups of up to five rats of the same sex in metal cages with wire mesh floors.
A standard Iaboratory rodent diet (Labsure LAD 1) and domestic quality potable water were provided ad libitum. Access to food only was prevented overnnight prior to and approximately 4 hours after dosing.
The mean daily minimum and maximum temperatures of the animal room were 22°C and 23°C respectively and the mean daily relative humidity value was 68% R.H. The rate of air exchange was maintained at approximately 15 air changes/hour. Lighting was controlled by means of a time switch to provide 12 hours artificial lÍght in each 24-hours period.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The appropriate dose volume of the test substance was administered to each rat using a syringe and plastic catheter (8 choke)

Doses:

Preliminary test: 0.80 and 2.50 g a.i./kg
Main study: 0.80, 1.26 and 2.00 g a.i./kg

No. of animals per sex per dose:

Preliminary test: 2 males and 2 females per dose
Main study: 5 males and 5 females per dose

Control animals:

no

Results and discussion

Preliminary study:

Mortality data for group of rats dosed orally with butyl benzotriazole-sodium salt (37% solution)

Dose (g a.i./kg) Mortality ratio (No; of deaths/No. dosed) Time of death after dosing
0.80; Male: 0/2; Female: 1/2; Combined: 1/4 ; Day 3
2.50; Male: 2/2; Female: 2/2; Combined: 4/4 ; < 4 h - < 22 h

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 400 mg/kg bw

Based on:

act. ingr.

95% CL:

>= 1 100 - <= 1 900

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 1 400 mg/kg bw

Based on:

act. ingr.

95% CL:

>= 1 000 - <= 2 400

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 1 300 mg/kg bw

Based on:

act. ingr.

95% CL:

>= 900 - <= 2 100

Mortality:

There was a single male death amongst rats dosed at 0.80 g a.i/kg and deaths amongst both sexes of rat treated at 1.26 g a.i./kg and above. The majority of rats died from within six hours of dosing until Day 4. A single male, treated at the low dose Ievel, was found dead on Day 10.

Autopsy of rats that died commonly revealed no macroscopic abnormalities. The only exception was the presence of brown Iiquid within the urinary bladder of a single male dosed at 2.00 g a.i./kg.

Clinical signs:

other: Common signs of reaction to treatment within four hours of dosing were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), Iethargy, decreased respiratory rate, ptosis, pallor of the extremities, increased salivation and pro

Gross pathology:

Autopsy of rats that died commonly revealed no macroscopic abnormalities. The only exception was the presence of brown Iiquid within the urinary bladder of a single male dosed at 2.00 g a.i./kg.

Other findings:

Terminal autopsy findings were normal.

Any other information on results incl. tables

Mortality data for groups of rats dosed orally with butyl benzotriazole-sodium salt (37% solution)

Main Study  Sex  Dose (g a.i./kg bw)  Number of deathsin a group of 5  Time of the death  Male  0.80  1  Day 10  Male  1.26  1  Day 2  Male  2.00  4  2 at 6 h of day 1; 2 at day 2  Female  0.80  0    Female  1.26  3  2 at day 2; 1 at day 4  Female  2.00  4  2 at 6 h of day 1; 2 at day 2

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute median lethal oral doses (LD50) and their 95% confidence limits to rats of butyl benzotriazole-sodium salt,dosed as a 37% solution,were estimated to be:
Males and females combined: 1.4 (1.1 to 1.9) g a.i./kg bodyweight.
Males only: 1.4 (1.0 to 2.4) g a.i./kg bodyweight.
Females only: 1.3 (0.9 to 2.1) g a.i./kg bodyweight.

The results of this study established that Butyl benzotriazole, sodium salt hac to be classified:
Harmful with the risk phrase R22 (harmful if swallowed), according directive 67/548/EEC (DSD)
Acute Tox. 4 with Hazardous Statement H302 (harmful if swallowed), according regulation (CE) 1272/2008 (CLP)

Executive summary:

A study was performed to assess the acute oral toxicity to rats of Butyl benzotriazole, sodium salt

The study was conducted in accordance wilth under Annex V of the EEC direcetíve 79/831/EEC, Part B Methods for determínation of toxicity, Method B1 Acute OraI Toxicity, and the OECD guideline for Testing of Chemicals No. 401 "Acute OraI Toxicity"

The acute median lethal oral doses (LD50) and their 95% confidence limits to rats of butyl benzotriazole, sodium salt, dosed as a 37% solution,were estimated to be:

Males and females combined: 1.4 (1 .1 to 1.9) g a.i./kg bodyweight.

Males only: 1.4 (1.0 to 2.4) g a.i./kg bodyweight

Females only: 1.3 (0.9 to 2.1) g.a.i./kg bodyweight

Main study shows

Mortality: There was a single male death amongst rats dosed at 0.80 g a.i/kg and deaths amongst both sexes of rat treated at 1.26 g a.i./kg and above. The majority of rats died from within six hours of dosing until Day 4. A single male, treated at the low dose Ievel, was found dead on Day 10.

Autopsy of rats that died commonly revealed no macroscopic abnormalities. The only exception was the presence of brown Iiquid within the urinary bladder of a single male dosed at 2.00 g a.i./kg.

Clinical signs: Common signs of reaction to treatment within four hours of dosing were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), Iethargy, decreased respiratory rate, ptosis, pallor of the extremities, increased salivation and prostration. Other clinical signs apparent at the same time or at later intervals on Day 1 were:

- ataxia amongst rats treated at all dose levels,

- increased lachrymation amongst females dosed at 0.80 g .i./kg and in all rats treated at 1.26 and 2.00 g.a.i/kg.

Recovery of rats surviving treatment, as judged by external appearance and behaviour, was apparently complete by Days 4 and 5 (0.80 and 1.26 g a.i./kg) or Day 7 (2.00 g a.i./kg).

Delayed signs of toxicity including pilo-erection , abnormal body carriage, abnormal gait, lethargy and pallor of the extremities reappeared on Day 9 in one male dosed at 0.80 ga.i./kg and preceded death on the following day.

Bodyweight: Low bodyweight gains during the first week of the study were recorded for all surviving rats.

Single male and female rats dosed at 0.80 and 1.26 g a.i./kg and a further male treated at the high dose level showed low bodyweight, gains between Days 8 and 15.

Terminal autopsy findings were normal

It is concluded that butyl benzotriazol, sodium salt has to be classifiedhas harmful with risk phrase R22 (DSD) and Acute Tox. 4 with hazardous Statement H302 (CLP/GHS)