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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 247-415-5 | CAS number: 26021-57-8
- 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
Acute Toxicity: oral
Administrative data
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 7 june 1989 to 24 november 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Version / remarks:
- 24 February 1987
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- no
Test material
- Reference substance name:
- 3,4-dihydro-2H-1,4-benzoxazin-6-ol
- EC Number:
- 247-415-5
- EC Name:
- 3,4-dihydro-2H-1,4-benzoxazin-6-ol
- Cas Number:
- 26021-57-8
- Molecular formula:
- C8H9NO2
- IUPAC Name:
- 3,4-dihydro-2H-1,4-benzoxazin-6-ol
- Test material form:
- solid: particulate/powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: OFA.SD. (lOPS Caw)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable) : not applicable
- Source: Iffa-Credo (69210 L'Arbresle- France)
- Females (if applicable) nulliparous and non-pregnant: yes
- Rationale for use of males (if applicable) : not applicable
- Age at study initiation: young adults between 5 and 7 weeks old
- Weight at study initiation: from 127 g to 172 g (the individual weights for each sex varied by no more than 20 % of the mean weights of the animals).
- Fasting period before study: test article was administered after about 17 to 18 hours of fasting (water regimen only). Animals received food again 4 hours after the administration.
- Housing: housed by sex and in groups of 5 in type MI polycarbonate cages (interior dimensions 365 x 225 x 180 mm);bedding changed once a week ; cages changed for each study
- Historical data: not specifed in the study report
- Diet (e.g. ad libitum): complete pelleted rat-mouse maintenance diet ad libitum (U.A.R., formule A.04 CR- U.A.R., Villemoisson- 91360 Epinay-S/Orge- France)
- Water (e.g. ad libitum): softened and filtered (15 m) mains drinking water ad libitum. Bacteriological and chemical analyses twice a year.
No known contaminant was present in the food or the at a concentration which could have prejudiced the study. Certificates and water analysis results are kept in the testing facility.
- Acclimation period: at least 8 days before the start of treatment
- Microbiological status when known : not specified in the study report
- Method of randomisation in assigning animals to test and control groups: they were taken from the animal house stock after the acclimatisation period and after weighing were allocated to groups according to weight in order to obtain homogeneous groups of each sex. They were then taken as they came to hand from these weight classified groups in order to obtain the required number of groups for the study.
Clinical examinations of animals were performed at reception then before the start of treatment to ensure that only healthy animals are included in the study.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°
- Humidity (%): 30 to 70 R.H
- Air changes (per hr): at least 10 per hour
- Photoperiod (hrs dark / hrs light): artificial, 12 hours out of 24 (photoperiod= 7h30- 19h30)
IN-LIFE DATES: From: To: not specified in the study report
.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- as a 0.5 % (W/V) dispersion in distilled water (house preparation)
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: test article in a 2.5 - 5.0 - 10.0 and 25.0 % (W/V) suspension in the vehicle.
- Amount of vehicle (if gavage): not specified
- Justification for choice of vehicle: vehicle requested by the sponsor
- Lot/batch no. (if required): 85133
- Purity: not specified
MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg of test article
DOSAGE PREPARATION (if unusual): not applicable
CLASS METHOD (not applicable) - Doses:
- 5000, 2000, 1000 and 500 mg/kg bw.
- No. of animals per sex per dose:
- 20 males and 20 non-pregnant females.
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: any deaths and abnormal clinical signs were noted 15 minutes after administration of the test article, then at 1, 2 and 4 hours and then daily for the 14 day study period detailing the nature and duration of any clinical signs observed. Animals were weighed the day before treatment (Day -1), immediately before administration of the test article (Day 1), at Days 8 and 15 as well as at time of death from Day 2 onwards.
- Necropsy of survivors performed: yes, performed in all animals that died during the study. After the 14 days study period and the final observation (Day 15), all surviving rats were killed by means of overdosing with carbon dioxide and then necropsied. The abdominal and thoracic cavities were opened and particular attention was paid to the·following organs: liver, heart, kidneys and lungs.
- Clinical signs including body weight: the daily observations performed, amongst others, included changes in the skin and fur, the eyes, mucous membranes, respiratory system, circulator system, autonomic and central nervous systems, as well as somata-motor activity and behaviour. Shivering, convulsions, salivation, diarrhoea, lethargy, sleeping and coma were noted with particular attention.
- Other examinations performed: none.
- Data analyisis:
-> The data were recorded indicating for each group employed the number of animals of each sex at the start of the study, the cumulative mortality for each observation period and for each sex, the number of animals presenting with signs of toxicity, a description of the toxic effects and the individual results of the necropsy examinations.
-> The body weights of the animals were evaluated for each group and each sex, calculating the mean of the values obtained, the standard deviation, the variation coefficient which indicates the homogeneity of the data.
The evaluation:- of these data included the relationship, if any, between exposure of the animals to the test article and the incidence as well as the severity of all abnormalities including changes in behaviour and clinical abnormalities, macroscopic lesions, changes in body weight, mortality and any other toxic effects.
-> LD50 calculation: taking into account the choice of the different dose levels, the dose level which is lethal for 50 out of 100 animals (LD 50) could only be estimated. The results of the LD 50 were expressed in mg of test article per kg of animal for both males and females combined. - Statistics:
- None.
Results and discussion
Effect levels
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 1 000 - < 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- Cumulative mortality rates were as follows:
Dose of 5000 mg/kg bw: 100%
Dose of 2000 mg/kg bw: 100%
Dose of 1000 mg/kg bw: 20%
Dose of 500 mg/kg bw: 0%
Details on mortality are presented in Table 1 in section "Any other information on results incl. tables". - Clinical signs:
- other: The following significant changes were noted: . at 5000 mg/kg: a comatose state associated with clonic convulsions was observed in all animals within 1/4 hour after treatment and in the 6 survivors at 1 hour, then lethargy was noted in the last survivor a
- Gross pathology:
- Areas of congestion were observed in the lungs of animals that died during the study. No abnormality was noted in the rats sacrificed at the end of the test (Day 15).
- Other findings:
- None.
Any other information on results incl. tables
Table 1. Cumulative mortality results
Dose level (mg/kg bw) |
Sex |
Day |
Total mortality (%) |
|||||||||||||||||
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
15 |
||||||
¼ H |
1H |
2H |
4H |
|||||||||||||||||
500 |
M |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
||
1000 |
M |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
20 |
F |
0 |
0 |
0 |
0 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
||
2000 |
M |
0 |
0 |
0 |
1 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
100 |
F |
0 |
1 |
3 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
5000 |
M |
0 |
1 |
4 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
100 |
F |
0 |
3 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Table 2. Evolution of the body weights
|
|
Day -1 |
Day 1 |
Day 8 |
Day 15 |
Day 15 - D -1 |
Dead |
|
Group 4 (500 mg/kg bw) |
||||||||
Males |
|
175 |
159 |
215 |
271 |
96 |
|
|
176 |
160 |
202 |
274 |
98 |
|
|||
187 |
164 |
234 |
288 |
101 |
|
|||
181 |
160 |
203 |
254 |
73 |
|
|||
174 |
153 |
204 |
259 |
85 |
|
|||
Mean |
178.60 |
159.20 |
211.6 |
269.20 |
90.60 |
|
||
S.D |
5.41 |
3.96 |
13.58 |
13.37 |
11.55 |
|
||
C.V. (%) |
3.03 |
2.49 |
6.42 |
4.97 |
12.74 |
|
||
t |
|
|
|
|
|
|
||
Females |
|
156 |
142 |
190 |
222 |
66 |
|
|
162 |
142 |
205 |
225 |
63 |
|
|||
151 |
137 |
183 |
218 |
67 |
|
|||
139 |
127 |
167 |
188 |
49 |
|
|||
153 |
138 |
179 |
195 |
42 |
|
|||
Mean |
152.20 |
137.20 |
184.80 |
209.60 |
57.40 |
|
||
S.D |
8.47 |
6.14 |
14.04 |
16.89 |
11.24 |
|
||
C.V. (%) |
5.56 |
4.48 |
7.60 |
8.06 |
19.58 |
|
||
t |
|
|
|
|
|
|
||
Group 2 (1000 mg/kg bw) |
||||||||
Males |
|
178 |
155 |
161 |
220 |
42 |
|
|
180 |
158 |
152 |
189 |
9 |
|
|||
190 |
166 |
169 |
226 |
36 |
|
|||
183 |
159 |
152 |
215 |
32 |
|
|||
175 |
156 |
145 |
190 |
15 |
|
|||
Mean |
181.20 |
158.80 |
155.80 |
208.00 |
26.80 |
|
||
S.D |
5.72 |
|
|
|
14.13 |
|
||
C.V. (%) |
3.16 |
2.72 |
5.98 |
8.33 |
52.73 |
|
||
t |
|
|
|
|
|
|
||
Females |
|
162 |
143 |
136 |
198 |
36 |
|
|
162 |
145 |
156 |
190 |
28 |
|
|||
168 |
148 |
*** |
*** |
*** |
146 |
|||
152 |
139 |
162 |
197 |
45 |
|
|||
158 |
141 |
*** |
*** |
*** |
140 |
|||
Mean |
160.40 |
143.20 |
151.33 |
195.00 |
36.33 |
|
||
S.D |
5.90 |
3.49 |
13.61 |
4.36 |
8.50 |
|
||
C.V. (%) |
3.68 |
2.44 |
9.00 |
2.24 |
23.41 |
|
||
t |
|
|
|
|
|
|
||
Group 3 (2000 mg/kg bw) |
||||||||
Males |
|
191 |
171 |
*** |
*** |
*** |
169 |
|
|
177 |
159 |
*** |
*** |
*** |
158 |
||
|
170 |
152 |
*** |
*** |
*** |
|
||
|
185 |
163 |
*** |
*** |
*** |
162 |
||
|
179 |
156 |
*** |
*** |
*** |
154 |
||
Mean |
180.40 |
160.20 |
|
|
|
|
||
S.D |
7.99 |
7.26 |
|
|
|
|
||
C.V. (%) |
4.43 |
4.53 |
|
|
|
|
||
t |
|
|
|
|
|
|
||
Females |
|
150 |
132 |
*** |
*** |
*** |
|
|
162 |
146 |
*** |
*** |
*** |
|
|||
155 |
138 |
*** |
*** |
*** |
|
|||
163 |
142 |
*** |
*** |
*** |
|
|||
157 |
142 |
*** |
*** |
*** |
|
|||
Mean |
157.40 |
140.00 |
|
|
|
|
||
S.D |
5.32 |
5.29 |
|
|
|
|
||
C.V. (%) |
3.38 |
3.78 |
|
|
|
|
||
t |
|
|
|
|
|
|
||
Group 3 (5000 mg/kg bw) |
||||||||
Males |
|
191 |
171 |
*** |
*** |
*** |
169 |
|
177 |
159 |
*** |
*** |
*** |
158 |
|||
170 |
152 |
*** |
*** |
*** |
|
|||
185 |
163 |
*** |
*** |
*** |
162 |
|||
179 |
156 |
*** |
*** |
*** |
154 |
|||
Mean |
180.40 |
160.20 |
|
|
|
|
||
S.D |
7.99 |
7.26 |
|
|
|
|
||
C.V. (%) |
4.43 |
4.53 |
|
|
|
|
||
t |
|
|
|
|
|
|
||
Females |
|
150 |
132 |
*** |
*** |
*** |
|
|
162 |
146 |
*** |
*** |
*** |
|
|||
155 |
138 |
*** |
*** |
*** |
|
|||
163 |
142 |
*** |
*** |
*** |
|
|||
157 |
142 |
*** |
*** |
*** |
|
|||
Mean |
157.40 |
140.00 |
|
|
|
|
||
S.D |
5.32 |
5.29 |
|
|
|
|
||
C.V. (%) |
3.38 |
3.78 |
|
|
|
|
||
t |
|
|
|
|
|
|
***: dead animal.
Applicant's summary and conclusion
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- Under the conditions of this study, the maximal non-lethal dose of hydroxybenzomorpholine was 500 mg/kg, the minimal lethal dose was 1000 mg/kg, and the median lethal dose (LD50) was between 1000 and 2000 mg/kg.
- Executive summary:
A single oral (gavage) 5000 mg/kg bw dose of the test substance to 5 week old rats (5 per sex) after overnight fasting. Due to the mortalities, 5 days later, further groups were dosed at 2000 and 1000 mg/kg bw as 10 and 5% (w/v) suspension, followed by a final group 14 days later, at 500 mg/kg bw dose as 2.5% (w/v) suspension.
Animals were observed at 15 min, 1, 2 and 4h and then daily for clinical signs and mortality. Body weights were recorded on the Day -1, 1, 8 and 15. Post-mortems were carried out on all animals. No organ/tissue samples were taken.
Results
All animals given 5000 mg/kg were found dead within 4 h. The initial effect of clonic convulsions and lethargy were noted in 15 minutes of dosing leading to coma and death.
All females and 1 male given 2000 mg/kg were found dead within 4 h. The remaining males were dead by Day 2. Lethargy and prostration were noted in the first 4 hours of dosing leading to coma and death after showing unconsciousness and clonic convulsions.
At 1000 mg/kg, 2 females were found dead on day 2, and all animals showed unconsciousness and prostration mainly on the day of dosing. Surviving animals resumed normal appearance and behaviour within day 8.
There were no deaths at 500 mg/kg, no body weight changes, and clinical signs were limited to prostration on the day of dosing.
Conclusion
Under the conditions of this study, the maximal non-lethal dose of hydroxybenzomorpholine was 500 mg/kg, The minimal lethal dose was 1000 mg/kg, and the median lethal dose (LD50) was between 1000 and 2000 mg/kg.
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.