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EC number: 239-269-6 | CAS number: 15217-42-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: study performed by regulatory organisation, but no guideline followed
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 978
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD 451
- Deviations:
- yes
- Remarks:
- only two dose groups
- Principles of method if other than guideline:
- Groups of animals are administered to the test substance for 78 weeks and observed for 26 weeks additionally.
Two dose groups and a control group are chosen per sex.
Body weights and clinical signs are collected and killed animals are pathologicaly examined - GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 1H-1,2,3-Benzotriazol
- IUPAC Name:
- 1H-1,2,3-Benzotriazol
- Reference substance name:
- Benzotriazole
- EC Number:
- 202-394-1
- EC Name:
- Benzotriazole
- Cas Number:
- 95-14-7
- Molecular formula:
- C6H5N3
- IUPAC Name:
- 1H-Benzotriazole
- Test material form:
- not specified
- Details on test material:
- - Name of test material (as cited in study report): 1H-Benzotriazole
- Molecular formula (if other than submission substance): C6H5N3
- Molecular weight (if other than submission substance): 119.14 g/mol
- Smiles notation (if other than submission substance): c12c(cccc1)N=NN2
- InChl (if other than submission substance): 1S/C6H5N3/c1-2-4-6-5(3-1)7-9-8-6/h1-4H,(H,7,8,9)
- Structural formula attached as image file (if other than submission substance):
- Distributor: Aldrich Chemical Company, Milwaukee, Wisconsin
- Analytical purity: >99 %
- Purity test date:
- Lot/batch No.: 122917 and 030737
- Storage condition of test material: 4 °C
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- second test animals:
Species : mice
Strain: B6C3F1
Sex: male/ female
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, Massachusetts
- Age at study initiation: 42 days (rat), 44 days (mice)
- Weight at study initiation: ca. 90 g (rat), ca. 20 - 25 g (mice)
- Fasting period before study: no
- Housing: steel wire-mesh cages, solid polycarbonate cages
- Diet: ground Wayne Lab Blox animal feed, ad libitum
- Water: Tap water (0.75 - 1 ppm chlorine), ad libitum
- Acclimation period: two weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-24 °C
- Humidity (%): no data
- Air changes (per hr): 6
- Photoperiod (hrs dark / hrs light): 12
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
Mixing a weighed amount of chmical with an aliquot of food in a mortar.
When the premix is homogeneous, it is blended with the remaining feed and
mixed for 20 min.
DIET PREPARATION
- Rate of preparation of diet (frequency): once a week
- Mixing appropriate amounts with (Type of food): Ground Wane Lab Blox animal feed
- Storage temperature of food: 4 °C - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analysis by ultraviolet spectroscopy at intervals of 2 - 6 weeks after mixing.
Concentrations were within 25 % of the theoretical value - Duration of treatment / exposure:
- 78 weeks
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
6700 ppm
Basis:
other: rats, nominal in diet, low-dose group; time-weighted average dose
- Remarks:
- Doses / Concentrations:
12100 ppm
Basis:
other: rats, nominal in diet, high-dose group; time-weighted average dose
- Remarks:
- Doses / Concentrations:
11700 ppm
Basis:
other: mice, nominal in diet, low-dose group; time-weighted average dose
- Remarks:
- Doses / Concentrations:
23500 ppm
Basis:
other: mice, nominal in diet, high-dose group; time-weighted average dose
- No. of animals per sex per dose:
- 50
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: based on subchronic study
- Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: every 2 weeks in the first 12 weeks, then every month - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table)
HISTOPATHOLOGY: Yes (see table) - Statistics:
- Probabilities of survival are estimated by the product-limit procedure of Kaplan and Meier (1958).
Statistical analyses for a possible dose-related effect on survial use the method of Cos (1972) and Tarone's (1975) extensions.
One-tailed P values have been reported for all tests except the departure from linearity test, which is only reported when its two-tailed P value is less than 0.05. The one-tailed Fisher exact test (Cox 1970) is used to compare the tumor incidence of a control group with that of a group of dosed animals at each dose level.
The Cochran-Armitage test for linear trend in proportions, with continuity correction (Armitage 1971) is also used
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- lowered mean body weights
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Rats:
Eye discoloration or inflammation up to two animals per group (also control).
Inflammation of the posterior ventral surface in one high-dose male.
Alopecia in one control male.
Survival ranged from 64 to 86 %, with the lower values observed in the control groups (For details see table 1)
Mice:
Alopecia in 1 low-dose female, 2 high-dose females, 27 control males, 30 control females
distension of the stomach in 1 control male and female
swelling and inflammation in the anal region in 1 low-dose male
abscess in the anal region in 1 high-dose male
poor balance at the end of study in 1 high-dose female
Survival ranged from 60 to94 %, with the lower values observed in the control groups (For details see table 2)
BODY WEIGHT AND WEIGHT GAIN
Rats:
Mean body weights of the dosed male and female rats were lower than those of the corresponding controls throughout most of the bioassay. A dose-related effect was generally indicated by the data for each sex, except for the last 24weeks in the females when the mean body weights of both the low- and high-dose groups gradually rose toward those of the controls.
Mice:
Mean body weights of the dosed male and female mice were lower than those of the corresponding controls throughout most of the bioassay, and a dose-related effect was indicated by the data for each sex.
PATHOLOGY (gross pathology, histopathology)
Rats:
Hepatic lesions observed in male and female rats consisted of neoplastic nodules of the liver in five males and two females from the high-dose groups. No animals in the control or low-dose groups had neoplastic nodules. Morphologic features of the neoplastic nodules were similar to those described in the literature. Neoplastic nodules were spherical lesions up to several liver lobules in size composed of plates of hepatocytes which were sharply demarcated and compressed the adjacent normal parenchyma. Hepatocytes within these nodules showed varying degrees of cytoplasmic change, including clear cell, eosinophilic, and basophilic alterations. Mitotic figures and varying degrees of nuclear atypia including multinucleation and hyperchromasia were noted. Brain lesions observed in rats as early as week 21 consisted of an oligodendroglioma in one low-dose male and gliomas in two low-dose males and one high-dose female. These tumors were not present in the control animals. In female rats a non-dose-related increase in the incidence of C-cell adenomas and carcinomas of the thyroid was noted. The incidence in the controls was 0/43, the low-dose group 5/43, and
the high-dose group 3/50. Most of the remaining neoplasms occurred randomly in control and dosed groups, and their incidences and types, with few exceptions, were similar to those observed historically in Fischer 344 rats. With the possible exception of the liver in male rats and the brain in male and female rats, no particular organ or system seemed to be the target of this chemical. One high-dose female had a rare and unusual neoplasm which appeared to be a primary nonchromaffin paraganglioma of the heart. The mass was visible microscopically in the wall of the left ventricle and was composed of sheets of cells arranged in small organoid-like packets. The cells had large oval and round vesicular nuclei, high nuclear cytoplasmic ratios, and a light gray-blue cytoplasm. The endocrine-like appearance of the mass suggested it might be a chemodectoma, since all efforts to
demonstrate chromaffin granules were negative. A variety of degenerative, proliferative, and inflammatory lesions were observed in the control and dosed rats, but none were believed to be related to administration of 1H-benzotriazole.
Mice:
In female mice, a non-dose-related increase in the incidence of alveolar/bronchiolar adenomas and carcinomas was noted. The incidence in the controls was 0/49, the low-dose group 10/49, and the high-dose group 4/49. The remaining neoplasms occurred randomly in control and dosed groups, and their incidence and type, with few exceptions, were similar to those observed historically in B6C3F1 mice. No particular organ or system seemed to be the target of this chemical. A variety of degenerative, proliferative, and inflammatory lesions were seen in the control and dosed mice.
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- ca. 6 700 ppm
- Based on:
- test mat.
- Remarks:
- nominal in diet, time weighted average in rats
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: Mean body weights of the dosed male and female (both species) were lower than those of the corresponding controls throughout most of the bioassay
- Dose descriptor:
- LOAEL
- Effect level:
- ca. 11 700 ppm
- Based on:
- test mat.
- Remarks:
- nominal in diet, time weighted average in mice
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: Mean body weights of the dosed male and female (both species) were lower than those of the corresponding controls throughout most of the bioassay
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1: Survival of rats
Group | absolute numbers | Survival |
high-dose males | 36/50 | 72 % |
low-dose males | 34/50 | 68 % |
control males | 32/50 | 64 % |
high-dose females | 43/50 | 86 % |
low-dose females | 40/50 | 80 % |
control females | 36/50 | 72 % |
Table 2: Survival of mice
Group | absolute numbers | Survival |
high-dose males | 42/50 | 84 % |
low-dose males | 36/50 | 72 % |
control males | 33/50 | 66 % |
high-dose females | 47/50 | 94 % |
low-dose females | 39/50 | 78 % |
control females | 30/50 | 60 % |
The recalculation of the dosage from ppm in food to mg/kg bw/day is performed according to Lehman, A.J. (1954). Association of Food and Drug Officials Quarterly Bulletin 18: 66.
rat: 6700 ppm = 335 mg/kg bw/day
12100 ppm = 605 mg/kg bw/day
Applicant's summary and conclusion
- Conclusions:
- Concerning the body weight gain, a LOAEL of 6700 ppm in rats and 11700 ppm in mice was observed. Organo-toxicological effects related to the substance were not observed. The LOAEL of 6700 ppm is equivalent to 335 mg/kg bw/day, 11700 ppm to 1755 mg/kg bw/day.
Although only two dose groups were administerd, the study is rated as reliable with restrictions. This deviation is considered as acceptable as long as a reasonable Assessment Factor is applied in order to account for Dose-response relationship.
Although administration of this chemical to rats may be associated with neoplastic nodules of the liver in male Fischer 344 rats, there was no convincing evidence, based on the histopathologic examination, that administration of 1H-benzotriazole was carcinogenic under the conditions of this bioassay.
In the B6C3F1 mouse, based on the histopathologic examination, there was no evidence for the carcinogenicity of IH-benzotriazole under the conditions of this bioassay. - Executive summary:
For Benzotriazole a well-conducted in vivo study is available showing a LOAEL of 325 mg/kg bw / day for the chronic repeated dose toxicity. The study was designed as carcinogenicity study.
This means that a similar result for Sodium Benzotriazolate can be anticipated.
Sodium Benzotriazolate has a LOAEL of 325 mg/kg bw/day for chronic repeated dose toxicity based on a read-across approach.
A DNEL for oral, dermal and/or inhalation route can be based on this information.
Classification and labelling are / are not needed for this endpoint.
A risk characterisation will be performed because the substance is classified for oral toxicity.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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