Registration Dossier
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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 406-850-2 | CAS number: 133855-98-8 BAS 480 F
- 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
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Jun 1991 (first study), Nov 1991 (second study)
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days)
- Version / remarks:
- Nov 1984
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- (2RS,3RS)-3-(2-chlorophenyl)-2-(4-fluorophenyl)-[(1H-1,2,4-triazol-1-yl)methyl]oxirane
- EC Number:
- 406-850-2
- EC Name:
- (2RS,3RS)-3-(2-chlorophenyl)-2-(4-fluorophenyl)-[(1H-1,2,4-triazol-1-yl)methyl]oxirane
- Cas Number:
- 133855-98-8
- Molecular formula:
- C17 H13 Cl F N3 O
- IUPAC Name:
- 1-{[(2R,3R)-3-(2-chlorophenyl)-2-(4-fluorophenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazole
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- none given
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dr. Karl Thomae, Biberach/Riss, FRG
- Age at study initiation: not specified
- Weight at study initiation: male: 253-283 g (first study), 264-280 g (second study); female: 218-241 g (first study), 211-224 g (second study)
- Fasting period before sacrifice: about 16 h
- Housing: single
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 9 days
DETAILS OF FOOD AND WATER QUALITY: The feed batches used in the study were tested for impurities. The drinking water has been regularly assayed for chemical contaminants.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12 (illumination: 6 am to 6 pm)
IN-LIFE DATES: From: May 27, 1991 (first study) and Nov 18, 1991 (second study) To: Jun 26, 1991 (first study), Dec 18, 1991 (second study)
Administration / exposure
- Type of coverage:
- semiocclusive
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.5% Tylose (cleaned sodium-carboxymethylcellulose in aqua bidest.)
- Details on exposure:
- TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: at least 10% of the bodu surface
- Type of wrap if used: (4 layers of absorbent gauze and an elastic dressing).
- Time intervals for shavings or clipplings: at least thrice a week. Only the first clipping was carried out at least 24 hours before the first application.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 ml/kg
- Concentration (if solution): 1.000; 400 and 100 mg/kg body. Volumes of test substance preparations and solvent (0.5% solution of Tylose CB 30.000 in aqua bidest.) to be applied were calculated for each animal once a week on the day of body weight determination.
- Constant volume or concentration used: yes
- Preparation interval: daily
VEHICLE
- Tylose CB 30.000
- Amount(s) applied (volume or weight with unit): 2 ml/kg
- Concentration (if solution): 0.5% - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- To verify the correctness of the concentrations and the homogeneity of the test substance preparations, samples of each concentration were sent for analysis at the beginning of each study section. The content of the active ingredient was determined by HPLC.
- Duration of treatment / exposure:
- 3 weeks
- Frequency of treatment:
- 6 h per day
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day
- Dose / conc.:
- 400 mg/kg bw/day
- Dose / conc.:
- 1 000 mg/kg bw/day
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
An acute oral toxicity study in the rat, an acute dermal toxicity study in the rat, an acute dermal irritation/corrosivity study to the intact dorsal skin of the white rabbit, and an acute irritation to the eye of the white rabbit
- Rationale for animal assignment (if not random): random
- Other: Treatment had been performed in two consecutive study sections. In the first study section 1,000 mg/kg body weight and in the second study section 400 and 100 mg/kg body weight have been administered. In both study sections respectively, a control group for comparison was used. - Positive control:
- not included
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily (before and after exposure)
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: daily (about 30 min after removal of the dressing)
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION: Yes
- Time schedule: weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
FOOD EFFICIENCY: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Day 21; Males and females first study June 26, 1991; males and females second study Dec 18, 1991
- Anaesthetic used for blood collection: No
- Animals fasted: Yes
- How many animals: all
- Parameters checked: Leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, differential blood count, thromboplastin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 21; Males and females first study June 26, 1991; males and females second study Dec 18, 1991
- Animals fasted: No
- How many animals: all
- Parameters checked: sodium, potassium, chloride, inorganic phosphate, calcium, urea, creatinine, glucose, total bilirubin, total protein, albumin, globulins, triglycerides, cholesterol, magnesium, ALT, AST, ALP, GGT
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- the exsanguinated animals were necropsied and assessed by gross pathology.
- Organ weights from all animals: liver, kidneys, spleen, testes and adrenal glands
HISTOPATHOLOGY: Yes
- Organs examined for all test groups and all animals: treated skin, normal skin, liver, kidneys, spleen
- all gross lesions: all animals affected per group - Statistics:
- Wilcoxon test, Kruskal-Wallis-H-test, Mann-Whitney-U-test, Kruskal-Wallis
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Dermal irritation:
- no effects observed
- Description (incidence and severity):
- No signs of irritation on the treated skin could be observed in test or control animals.
Adhesive tape caused mechanical skin lesions beside the treated area. - 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):
- - 1000 mg/kg bw/day: slight decrease in red blood cells and hematocrit in the peripheral blood in males
No substance—induced changes were observed in the clotting analyses of both sexes - Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- No substance-induced changes were observed in the enzyme activities of both sexes. No substance—induced changes were observed in the clinicochemical examinations of both
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- - 1000 mg/kg bw/day: significantly increased absolute mean liver weights in male and female rats; significantly increased absolute mean kidney weight in female rats, without a morphological equivalent
- 400 mg/kg bw/day: significantly increased relative mean liver weight in female rats, without a morphological equivalent - Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- - 1000 mg/kg bw/day: slight centrilobular liver cell hypertrophy in male rats
- Details on results:
- The application of 1000 mg/kg body weight to the skin resulted in a treatment related increase of the absolute liver weight in male female rats. In males, a slight (grade 2) hypertrophy of the hepatocytea is in accordance with
the weight increase. Although no morphological alteration was noted in the females, the weight increase most likely represents a treatment related effect, too.
In contrast to this, the observed significant increase of the absolute weight of the testes does not represent a treatment related effect, as two control animals had exceptional low testes weights — due to spontneous tubular atrophy - and hence the mean value of dose group 1 was compared with a too low mean valuein the concurrent control group 0.
Although no morphological observation was made that may explain the significantly increased mean absolute kidney weights in the female rats of dose group 1000 mg/kg, it can not be excluded that this observation represents a marginal toxic effect. Its biologic relevance, however, is of little if any importance. No treatment related effects were seen in the treated skin.
In the untreated skin of the abdomen of one control and four treated females of dose group 1000 mg/kg, crust formation was noted grossly in the abdominal region where the adhesive fleece of the semiocclusive dressing stuck to the skin. This gross lesion proved to be hyperkeratosis, focal acanthosis, crust formation, focal necrosis, and/or dermal fibrosis histopathologically. None of these findings represent a treatment related effect as they are only linked with the technical procedure used for the application of the test article to the treated
site of the skin.
In the second part of the study (control group 00 and dose groups 3 [100 mg/kg body weight] and 2 [400 mg/kg body weight]), the only possible treatment related effect might be traced from the significantly increased relative live: weight of the female rats of dose group 2 (400 mg/kg body weight). However, no microscopic finding was noted that may refer to the increased weight. Moreover, the application
of 1000 mg/kg body weight to the skin did not result in significantly increased relative liver weights in the female rats. Therefore, the significance of this observation is of little if any biological relevance.
The increased absolute kidney weights in the females of dose group 3 are a by chance observation as the mean of this group is lower than that one of dose group 2 which does not show a statistically significant deviation from the concurrent control group 00.
All other gross lesions or microscoPic findings are regarded to have occurred incidentally and they could not be related to the application of the test article.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed
Target system / organ toxicity
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 400 mg/kg bw/day
- System:
- hepatobiliary
- Organ:
- liver
- Treatment related:
- yes
- Dose response relationship:
- yes
Any other information on results incl. tables
Table 1: Absolute weights of test groups 0 (control) and 1 (1000 mg/kg bw/day)
ABSOLUTEWEIGHTS- MEANVALUES (FEMALE)-GROUPS 0AND1
Sacrifice |
|
group |
Fl |
|
||
|
|
Sex |
F |
|||
Dose |
|
group |
0 |
1 |
||
Body weight |
g |
M |
220.22 |
228.5 |
||
|
|
|
SD |
8.327 |
16.833 |
|
|
|
|
n |
5. |
5. |
|
Liver |
|
g |
M |
7.278 |
8.788* |
|
|
|
|
SD |
0.44 |
1.348 |
|
|
|
|
n |
5. |
5. |
|
Kidneys |
|
g |
M |
1.876 |
2.076** |
|
|
|
|
SD |
0.107 |
0.094 |
|
|
|
|
n |
5. |
5. |
|
Spleen |
|
g |
M |
0.54 |
0.526 |
|
|
|
|
SD |
0.02 |
0.121 |
|
|
|
|
n |
5. |
5. |
|
Adrenal |
glands |
mg |
M |
103.6 |
111. |
|
|
|
|
SD |
11.739 |
7.517 |
|
|
|
|
n |
5. |
5. |
|
ABSOLUTE WEIGHTS - MEAN VALUES (MALE) - GROUPSOAND1
Sacrifice |
group |
Fl |
|
||
|
Sex |
M |
|||
Dose |
group |
0 |
1 |
||
Body weightg |
M |
291.44 |
306.56 |
||
|
SD |
16.477 |
11.225 |
||
|
n |
5. |
5. |
||
Liver |
g |
M |
10.142 |
11.428** |
|
|
|
|
SD |
0.702 |
0.169 |
|
|
|
n |
5. |
5. |
Kidneys |
|
g |
M |
2.486 |
2.622 |
|
|
|
SD |
0.186 |
0.118 |
|
|
|
n |
5. |
5. |
Testes |
|
g |
M |
2.844 |
3.108* |
|
|
|
SD |
0.237 |
0.178 |
|
|
|
n |
5. |
5. |
Spleen |
|
g |
M |
0.594 |
0.682 |
|
|
|
SD |
0.074 |
0.064 |
|
|
|
n |
5. |
5. |
Adrenal |
glands |
mg |
M |
86.8 |
80.4 |
|
|
|
SD |
14.255 |
12.502 |
|
|
|
n |
5. |
5. |
Wilcoxon-Test (two-sided)
* P<=0.05 ** P<=0.01
Table 2: Relative weights of test groups 00 (control), 3 (100 mg/kg bw/day), and 2 (400 mg/kg bw/day)
RELATIVE WEIGHTS - MEAN VALUES (FEMALE) GROUPS 00, 3 AND2
Sacrifice group |
|
|
Fl |
|
||||||
Sex |
|
|
F |
|
|
|
|
|||
Dosegroup |
|
|
00 |
|
3 |
2 |
|
|||
Body weight |
M |
100. |
|
100. |
|
100. |
|
|||
|
|
SD |
|
|
|
|||||
|
|
n |
5. |
5. |
5. |
|||||
Liver |
% |
M |
3.394h |
3.544 |
3.686** |
|||||
|
|
SD |
0.063 |
0.241 |
0.186 |
|||||
|
|
n |
5. |
5. |
5. |
|||||
Kidneys |
|
M |
0.877 |
0.921 |
0.903 |
|||||
|
|
SD |
0.015 |
0.049 |
0.097 |
|||||
|
|
|
n |
5. |
5. |
5. |
|
|||
Spleen |
|
% |
M |
0.265 |
0.293 |
0.254 |
|
|||
|
|
|
SD |
0.032 |
0.039 |
0.048 |
|
|||
|
|
|
n |
5. |
5. |
5. |
|
|||
Adrenal |
glands |
% |
M |
0.049 |
0.051 |
0.053 |
|
|||
|
|
|
SD |
0,005 |
0.004 |
0.009 |
|
|||
|
|
|
n |
5. |
5. |
5. |
|
|||
h P<=0.05 |
|
|
:Kruskal-Wallis-H-Test |
* P<=0.05** |
P |
<=0.01 |
:Kruskal-Wallis-H-+Wilcoxon-Test |
two-sided |
|
|
|
Applicant's summary and conclusion
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.