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EC number: 265-004-9 | CAS number: 64665-57-2
- 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
Endpoint summary
Administrative data
Description of key information
One orale subaute toxicity study is available, giving a NOAEL of 150 mg/kg bw/day.
As the former read-across to the proposed analogueous substance Benzotriazole (CAS 95-14-7) proofed to be
scientifcly not adequate, a read-across based on a category developed in OECD QSAR Toolbox
was used to fulfill the data gap which arose.
Category read-across Predictions taking into account studies with durations > 28 d
resulted in dose descriptors for the two main constituents.
While 4-Methyl-1H-Benzotriazole was predicted to have a NOAEL/NOEL of 435 resp. 168 mg/kg bw/day,
the results for 5-Methyl-1H-Benzotriazole are more consistent:
Ttwo predictions were made, one included substances for which a NOEL is available and one prediction
with substances with a NOAEL.
Both predictions resulted in a NOEL/NOAEL for 5-Methyl-1H-Benzotriazole (repeated dose toxicita, duration > 28 d) of
19 mg/kg bw/day.
However this information cannot be used for Hazard conclusion, as the approach does not give information on target organ(s) and
details of effects.
As a test is proposed, the information from this read across approach could be used for dose selection.
In a prenatal developmental toxicity study, a NOAEL of 90 mg/kg bw/day for systemic toxicity was determined.
For Hazard and risk assessment the lowest dose descriptor available is used.
A recalculation from the constituent to the substance, taking into account the typical concentration of the constituent
is not performed.
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Sodium Tolyltriazolate is expected to have a similar repeated dose toxicity over 28-days compared to the analogue Tolyltriazole resulting in a similar no observed adverse effect level (NOAEL), which is 150 mg/kg bw/day. The NOAEL of Tolyltriazole was determined in a well performed study. The source chemical Tolyltriazole is sufficiently similar to read-across towards Sodium Tolyltriazolate.
- Reason / purpose for cross-reference:
- read-across source
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Frequency of treatment:
- daily
- 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
- Basis for effect level:
- clinical biochemistry
- haematology
- Critical effects observed:
- not specified
- 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 - 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 Tolyltriazolate can be anticipated.
Sodium Tolyltriazolate 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 labelling are / are not needed for this endpoint.
A risk characterisation will be performed because the substance is classified for orale toxicity.
Reference
1. Source Chemical(s)
Benzotriazoles have two fused rings, one 1,2,3-triazole and one benzene ring. In Tolyltriazole, the benzene ring is substituted with one methyl group, while in Benzotriazole all substituents are hydrogen.
The Benzotriazoles can be deprotonated at the Nitrogen, leading to the conjugated base as sodium salt.
The differences in the chemical structure (from Benzotriazole to Tolyltriazole) are not expected to change the toxicological properties significantly.
The sodium salts are more basic than the neutral substances (Benzotriazole and Tolyltriazole) and present therefore irritant and corrosive properties, as seen in in vivo studies. Nevertheless, systemic effects are expected to be comparable between the salts and the neutral substances due to the fact that in physiological environment (pH 6-8) protonation of the slat occurs and the neutral species is yielded.
2. Purity/impurities
The impurities in the target substance do not indicate toxicological relevence to this endpoint. The impurities are all below 1 %.
The excess sodium hydroxide of sodium benzotriazolate and sodium tolyltriazolate increases the toxicological irritation/corrosion properties as seen in valid in vivo tests. Further on, it is assumed that no other influence then the basic reservoir is changed by this impurity
3. Analogue approach justification
According to Annex XI, 1.5 a read-across approach can be used to fill the data gap when certain criteria are fulfilled. The fulfillment of these criteria is discussed below. The information from the REACH technical guidance document R.6 are used for this assessment as well as ECHA's Practical guide 6 on category and read-across approaches (ECHA REACH TGD; ECHA, 2009).
Quality of the experimental data of the analogues
The source chemical has been tested in a well-conducted study (According to OECD TG 407). The study results receive reliability 1.
Toxicokinetics
The source and target chemicals indicate similarity in toxicokinetic behavior based on the molecular weight (< 200), physical form (all are solids), vapor pressure (< 10 Pa) and Log POW(0-2).
The difference between the neutral species and the salts in respect to log POWis in the range of 1 and expected to be of minimal relevance. The charge of the Benzotriazolate anion in the salts will decrease the bioavailability but in contact with water the neutral species will be formed in dependence of the pH.
Reactivity towards proteins and DNA
(Q)SAR modeling
The (Q)SAR modeling as such is not used for predictivity but it is used for showing that the Benzotriazoles have the same toxicological profile according to these models.
The OECD (Q)SAR toolbox program is used to obtain the toxicological profile for the source and target substances.
The benzotriazole structures result in two alerts with regard to toxicity:
- Toxic Hazard Classification by Cramer: High (Class III)
- In vivo mutagenicity (Micronucleus) alerts by ISS: H-Acceptor-path 3-H-acceptor for DNA-binding for in vivo mutagenicity.
No alerts were found for DNA or protein binding.
The Toxic Hazard Classification by Cramer: High (Class III) is verified by the observed oral toxicity of the different benzotriazoles (data matrix).
The “in vivo mutagenicity (Micronucleus) alert by ISS” is a false positive alert as the available in vivo genetic toxicity data is negative for this endpoint.
Similarities in results for toxicological endpoints between the target and the source chemical(s) to support read-across for acute dermal toxicity
As it is presented in the data matrix the acute oral toxicity is in the same range for the target and source chemical(s).
The neutral substances (Benzotriazole and Tolyltriazole) show no skin irritation, skin sensitization properties and only mild eye irritation, the salts (Sodium benzotriazolate and sodium tolyltriazolate) show severe skin irritation / corrosion which is caused by the high basicity and the pH of a solution of these substances.
The negative genotoxicity profile is also similar between the source and the target chemical.
For Benzotriazole the Ames test, the mammalian mutation test and the mouse micronucleus test are negative.
For Tolyltriazole the Ames test and the mouse micronucleus test are negative.
Systemic toxicity is seen for Benzotriazole in a two year study and for Tolyltriazole in a 28 days-repeated dose test. No target organ was identified.
A LOAELchronicof 325 mg/kg bw for Benzotriazole and a NOAELsub-acuteof 150 mg/kg bw for Tolyltriazole was established.
Toxicity to reproduction and fertility was tested in a Screening test according to OECD Guideline 421 for Benzotriazole. In this study, a NOAELReprotox-screeningof 200 mg/kg bw/day was found. Higher doses were not tested due to the systemic toxicity of the substance.
4. Data matrix (IUCLID: „Results and discussion“)
Separate document
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 150 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- The study is a well conducted GLP-Study following the OECD-Guideline
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
Mode of Action Analysis / Human Relevance Framework
based on the available data, no mode of action can be identified.
Additional information
Justification for classification or non-classification
Based on the available data and the low severity of effects observed in experimental studies, criteria for classification is not met.
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.
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