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EC number: 223-445-4 | CAS number: 3896-11-5
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Treatment of dams was limited to gestation periods Day 6-15 of gestation only as opposed to a day before scheduled kill - certain maternal parameters not checked e.g corpora lutea was not determined.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 976
- Report date:
- 1976
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- (test substance administered on day 6-15 of gestation only, certain maternal parameters not checked e.g corpora lutea was not determined)
- Principles of method if other than guideline:
- The test compound was administered orally to pregnant rats from day 6 until 15 of gestation. Dams were observed during the pregnancy and then killed on day 21 of the pregnancy and an autopsy performed to examine the dam and the foetuses.
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Bumetrizole
- EC Number:
- 223-445-4
- EC Name:
- Bumetrizole
- Cas Number:
- 3896-11-5
- Molecular formula:
- C17 H18 Cl N3 O
- IUPAC Name:
- 2-tert-butyl-6-(5-chloro-2H-benzotriazol-2-yl)-4-methylphenol
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): TK 10048
- Physical state: solid
- Lot/batch No.: EN 26580 (1/75)
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Closed SPF breeding colony
- Age at study initiation: not stated
- Weight at study initiation: 240 g
- Fasting period before study: not stated
- Housing: Macrolon cages
- Diet: ad libitum; Nafag No. 890
- Water: ad libitum; tap water
- Acclimation period: not stated
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 0.5
- Humidity (%): 60 ± 5
- Air changes (per hr): air-conditioned room
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- (2%, aqueous)
- Details on exposure:
- VEHICLE
- Justification for use and choice of vehicle (if other than water): not stated
- Amount of vehicle (if gavage): 1mL/100 g bw
- Lot/batch no. (if required): not stated
- Purity: not stated - Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1:3
- Length of cohabitation: overnight
- Further matings after two unsuccessful attempts: no data
- Verification of same strain and source of both sexes: yes, the albino rats were Sprague -Dawley derived and obtained from a closed SPF breeding colony
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- Day 6 until day 15 of pregnancy inclusive.
- Frequency of treatment:
- once daily
- Duration of test:
- 21 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 300 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 3 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 25 females
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: not stated
- Rationale for animal assignment (if not random): not stated
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: daily
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes, a mean food consumption graph was present in the study, but no details about individual animal food consumption.
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No, as not a feeding study.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21
- Organs examined: Assessment of the dam's organs, especially the ovaries and uterus.
OTHER:The foetuses were subjected to careful external inspection and the condition of their body orifices was checked. They were then weighed individually followed by examination of the viscera and skeletal assessment. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Not stated
- Number of corpora lutea: No
- Number of implantations: Yes
- Number of early resorptions: Yes
-Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 2/3 per litter
- Head examinations: No - Statistics:
- Some statistics were present in the tables, although not in much detail. Standard deviation was only applied to weight of live foetuses. Confidence limits of the CMC-control for the skeletal assessment was present.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
No reactions to treatment were observed. Body-weight gain and food consumption were comparable for all groups.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 3 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 3 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
The implantation ratio and embryolethality were comparable for all groups. The average body weights of foetuses in each group were not significantly different from controls. Histopathology revealed the following minor anomalies: Two foetuses of one litter from the 300 mg/kg dose group showed either hypoplasia of the lungs or slight oedema-like changes of subcutaneous tissue (anasarca). One foetus from the 3000 mg/kg dose group and one from the vehicle control also showed hypoplasia. The aforementioned types of minor anomalies were also found in the cumulative control at incidences of 0.4% (hypoplasia of lungs) and 1.3% (anasarca). Based on these findings, no substance-related effect on embryonic or foetal development is assumed.
Skeletal assessment did not reveal any clearcut differences between the foetuses of the experimental group and those of the vehicle control.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 3 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
Table 1: Results of uterus examinations.
|
Dose groups (mg/kg bw) |
||||
|
Historical controls |
300 |
1,000 |
3,000 |
Control |
No. of dams |
510 |
25 |
25 |
25 |
25 |
Spontaneous deaths |
0 |
0 |
0 |
0 |
0 |
No of females with implantations |
453a |
24 |
24 |
24 |
23 |
Mean No. of implantations |
13.18 |
14.33 |
14.13 |
13.88 |
12.87 |
Embryonic resorptions (%) |
6.7 |
9.0 |
11.2 |
7.2 |
11.8 |
Foetal resorptions (%) |
0.1 |
0.3 |
0.3 |
0 |
0.3 |
Dead foetuses (%) |
0.1 |
0.6 |
0 |
0 |
0.3 |
Live foetuses (%) |
93.1 |
90.1 |
88.5 |
92.8 |
87.9 |
Live foetuses with malformations |
10 / 5,546b |
0 / 310 |
0 / 300 |
0 / 309 |
0 / 259 |
Mean weight of live foetuses (g) |
5.25 ± 0.44 |
5.19 ± 0.39 |
5.18 ±0.38 |
5.28 ± 0.39 |
5.20 ± 0.45 |
(a) Including one female with totally aborted litter (not taken into further consideration of data)
(b) Two cleft palates (one associated with mandibular hypoplasia), 2 mandibular aplasias, 3 general oedemas, 3 “open eyes”
Table 2: Skeletal changes in the foetuses.
Dose group (mg/kg bw) |
No. of skeletons examined |
Phalangeal nucleia |
Calcaneusa |
Sternebraed |
Vertebraee |
Vertebraef |
Sternebraeg |
Ribs |
|
|
|
Fore limb |
Hind limb |
|
|
|
|
|
|
Control |
173 |
3 (1.7) |
39 (22.5) |
33 (19.1) |
48 (27.7) |
0 |
1 (0.6) |
1 (0.6) |
1 (0.6)j |
300 |
208 |
4 (1.9) |
69 (33.2) |
75 (36.1) |
56 (26.9) |
1 (0.5) |
0 |
0 |
0 |
1,000 |
200 |
2 (1.0) |
34 (17.0) |
48 (24.0) |
60 (30.0) |
1 (0.5) |
0 |
0 |
1 (0.5)h |
3,000 |
205 |
6 (2.9) |
32 (15.6) |
23 (11.2) |
73 (35.6) |
0 |
0 |
0 |
1 (0.5)i |
|
|
|
|
|
|
|
|
|
|
99 % confidence limits of the controls n= 170 |
|
0.2 – 6.31 |
15.15 – 32.21 |
12.19 – 28.29 |
19.22 – 37.3 |
0.00 – 3.07 |
0.00 – 4.29 |
0.00 – 4.29 |
0.00 – 4.29 |
Figures in parenthensis represent %.
a) ossification
b) proximal phalanges V
c) proximal phalanges
d) particularly ossification centres of the 5thsternebrae still incompletely ossified (bipartite)
e) centres of some throracic vertebrae still dumbbell-shaped
f) centres of some throracic vertebrae bipartite
g) centres displaced and irregularly ossified
h) Basal fusion of left ribs 10 + 11
i) Bifurcation of right rins no. 13
j) Navy rib no. 13 (right)
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.
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