Sodium 1H-benzotriazolide

Endpoint summary

Description of key information

Read across from two studies (one sub-acute, one chronic) for the oral route,
one 14 day Range-finding study available supporting the Read across.
The selected NOAEL of 150 mg/kg bw/day is observed in the sub-acute study for the analogue Tolyltriazole.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Versuchstierzucht Winkelmann, Borchen
- Age at study initiation: 5 - 6 weeks
- Weight at study initiation: mean: 89 g (male) 86 g (female)
- Fasting period before study: no
- Housing: standard Makrolon-cages type II
- Diet: Altromin 1324 Pellets, ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 2 °C
- Humidity (%): 50 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: the test item was grounded and solved in the vehicle

DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:

VEHICLE
- Justification for use and choice of vehicle (if other than water): the test item is soluble and stable in the vehicle which is commonly used
- Concentration in vehicle: 10 to 90 mg / ml
- Amount of vehicle (if gavage): 5 ml / kg bw

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The stability of the test item in the vehicle was determined and no significant changes of the composition was observed after 48 hours.

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
0 mg/kg
Basis:
actual ingested

Remarks:

Doses / Concentrations:
50 mg/kg
Basis:
actual ingested

Remarks:

Doses / Concentrations:
150 mg/kg
Basis:
actual ingested

Remarks:

Doses / Concentrations:
450 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

6

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: the doses were selected based on a range finding study

Positive control:

No

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once or twice daily

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes

HAEMATOLOGY: Yes
- Time schedule for collection of blood: only at end of study
- Animals fasted: Yes
- How many animals: all

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: only at end of study
- Animals fasted: Yes
- How many animals: all

OTHER:

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

arithmetic means and standard deviation
for organ weights the confidence levels 95 and 99 %
Comparision of test and control group results are done with test of significance (U-test) with a= 5 % and a = 1%

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

in 450 mg/kg bw groups

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
one animal (450 mg/kg bw, female) died during the study
after the daily application, all animals in the dose group of 450 mg/kg bw showed apathy

BODY WEIGHT AND WEIGHT GAIN
no findings

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
no findings

HAEMATOLOGY
no findings in the dose groups 50 and 150 mg/kg bw
reduced levels of eryhtocytes, hematocrit and hemoglobine in the male dose group 450 mg/kg bw

CLINICAL CHEMISTRY
Raised activity of alanin-aminotransferase in male/female dose group 450 mg/kg bw
Reduced concentration of the plasma protein concentration in male/female dose group 450 mg/kg bw

ORGAN WEIGHTS
no findings

GROSS PATHOLOGY
two male and one female animal had pale kidneys

HISTOPATHOLOGY: NON-NEOPLASTIC
no findings


OTHER FINDINGS

Dose descriptor:

NOAEL

Effect level:

ca. 150 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Critical effects observed:

not specified

Conclusions:

Benzotriazole has a NOAEL of 150 mg/kg bw for the 28 days repeated dose toxicity.

Executive summary:

For Tolyltriazole a well-conducted in vivo study is available showing a NOAEL of 150 mg/kg bw for the 28 days repeated dose toxicity. This means that a similar result for Sodium Benzotriazolate can be anticipated.

 

Sodium Benzotriazolate has a NOAEL of 150 mg/kg bw for the 28 days repeated dose toxicity.

 

A DNEL for oral, dermal and/or inhalation route can be based on this information.

Classification and labeling are / are not needed for this endpoint.

A risk characterisation will be performed because the substance is classified for oral toxicity.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

150 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Two studies from analogues (Benzotriazole and Tolyltriazole) available.
A 14-day Range-finding study for the substance is available and supports the selection (A LOEL of 183.6 mg/kg bw/day was derived).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
No study for sub-acute or sub-chronic repeated dose toxicity available for this substance.
The sub-acute study of the analogue Tolyltriazole is selected as it provides the most sensitive NOAEL

Justification for classification or non-classification

The information on repeated dose toxicity are conclusive but not sufficient for a classification according Regulation (EC) No. 1272/2008.