Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD-Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Reference substance name:
Methylbenzotriazol
IUPAC Name:
Methylbenzotriazol
Constituent 2
Chemical structure
Reference substance name:
Methyl-1H-benzotriazole
EC Number:
249-596-6
EC Name:
Methyl-1H-benzotriazole
Cas Number:
29385-43-1
Molecular formula:
C7H7N3
IUPAC Name:
5-methyl-1H-1,2,3-benzotriazole
Test material form:
other: granules
Details on test material:
- Name of test material (as cited in study report): Preventol CI 7-100

- Physical state: solid
- Analytical purity: 99.2 %
- Composition of test material, percentage of components: 40 % 4- Methylbenzotriazole, 60 % 5- Methylbenzotriazole
- Lot/batch No.: 868
- Storage condition of test material: room temperature

Test animals

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: the test item was gounded 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
Doses / concentrationsopen allclose all
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

Examinations

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%

Results and discussion

Results of examinations

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

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
ca. 150 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical biochemistry
haematology

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In doses up to 150 mg/kg bw / day, no adverse effects were observed.
A dose of 450 mg/ kg bw/day lead to apathy after gavage, to a changed blood count and raised plasma activity of transaminases GOT and GPT