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EC number: 801-694-5 | CAS number: 1392325-86-8
- 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:
- The study was conducted between 23 April 2014 and 28 May 2014.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
- Version / remarks:
- 2001
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- fixed dose procedure
- Limit test:
- yes
Test material
- Reference substance name:
- 7,7,8,9,9-pentamethyl-5H,6H,6aH,7H,8H,9H,9aH-cyclopenta[h]quinazoline
- EC Number:
- 801-694-5
- Cas Number:
- 1392325-86-8
- Molecular formula:
- C16H24N2
- IUPAC Name:
- 7,7,8,9,9-pentamethyl-5H,6H,6aH,7H,8H,9H,9aH-cyclopenta[h]quinazoline
- Test material form:
- other: Solid
- Details on test material:
- Identification: IFF TM 12-206 (FRET 10-0199)
Description: White solid block
Storage conditions: Approximately 4 °C, in the dark
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatization period of at least five days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The body weight variation did not exceed ±20% of the body weight of the initially dosed animal.
The animals were housed in groups of up to five in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- DMSO
- Details on oral exposure:
- For the purpose of the study the test item was freshly prepared, as required, as a solution in dimethyl sulphoxide. Dimethyl sulphoxide was used because the test item did not dissolve/suspend in distilled water or arachis oil BP.
The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement. - Doses:
- Following a sighting test at dose levels of 2000 mg/kg and 300 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a solution in dimethyl sulphoxide, at a dose level of 2000 mg/kg body weight. Due to mortalities and signs of systemic toxicity at a dose level of 2000 mg/kg, an additional group of five animals was similarly treated at a dose level of 300 mg/kg body weight.
- No. of animals per sex per dose:
- Sighting test at dose levels of 2000 mg/kg and 300 mg/kg: One per dose
Main test at dose levels of 2000 mg/kg: Four per dose
Main test at dose levels of 300 mg/kg: Five per dose - Control animals:
- no
- Details on study design:
- Using available information on the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
A single animal was treated as follows:
300 mg/kg (at a concentration of 30 mg/mL) at a dose volume of 10 mL/kg administered to 1 female rat.
In the absence of mortality at a dose level of 300 mg/kg, an additional animal was treated as follows:
2000 mg/kg (at a concentration of 200 mg/mL) at a dose volume of 10 mL/kg administered to 1 female rat.
In the absence of mortality at a dose level of 2000 mg/kg, an additional group of animals was treated as follows:
2000 mg/kg (at a concentration of 200 mg/mL) at a dose volume of 10 mL/kg administered to 4 female rats.
A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.
Due to mortality and signs of systemic toxicity at a dose level of 2000 mg/kg, an additional group of animals was treated as follows:
300 mg/kg (at a concentration of 30 mg/mL) at a dose volume of 10 mL/kg administered to 5 female rats.
A total of six animals were therefore treated at a dose level of 300 mg/kg in the study.
Due to a technician error and Study Director oversight, the final group of animals, treated at a dose level of 300 mg/kg body weight, comprised of five animals instead of the required four animals meaning that a total of six animals were treated at this dose level instead of the required five. This deviation was considered not to affect the purpose or integrity of the study.
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose level to confirm the survival of the previously dosed animals.
Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and then daily for up to fourteen days. Morbidity and mortality checks were made twice daily.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.
At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Results and discussion
Effect levels
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 300 - 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- Dose Level - 2000 mg/kg
Two animals were found dead 1 or 4 days after dosing. One animal was killed for humane reasons, 6 days after dosing, due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence.
Dose Level - 300 mg/kg
One animal was killed for humane reasons, during the day of dosing, due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence. - Clinical signs:
- other: Dose Level - 2000 mg/kg Signs of systemic toxicity noted were hunched posture, lethargy, pilo erection, decreased respiratory rate, labored respiration, splayed or tiptoe gait, occasional body tremors, ataxia, dehydration, diarrhea and emaciation. Dose
- Gross pathology:
- Dose Level - 2000 mg/kg
Abnormalities noted at necropsy of animals that died or were humanely killed during the study were dark liver or patchy pallor of the liver, dark kidneys, solid substance present in the stomach, epithelial sloughing of the gastric mucosa and hemorrhagic non glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.
Dose Level - 300 mg/kg
Clear liquid or solid substance present in the stomach and thickened non glandular epithelium were noted at necropsy of the animal that was humanely killed during the study. No abnormalities were noted at necropsy of animals that were killed at the end of the study.
Any other information on results incl. tables
Individual Clinical Observations and Mortality Data -2000mg/kg
Dose Level mg/kg |
Animal Number and Sex |
Effects Noted After Dosing |
Effects Noted During Period After Dosing |
||||||||||||||||
½ |
1 |
2 |
4 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
||
2000 |
2-0 Female |
H |
HLRd |
HPL |
HLP |
HPWt |
H |
H |
H |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
3-0 Female |
HWs |
WsToL |
WsL |
WsL |
HLA |
HRl |
HRl |
H |
H |
HRdEm |
|
|
|
|
|
|
|
|
|
3-1 Female |
Ws |
WsToL |
WsL |
WsL |
HLA |
HRl |
HRl |
H |
H |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3-2 Female |
Ws |
HLA |
HLA |
WsL |
HLA |
HRlRd |
HRlRd |
X |
|
|
|
|
|
|
|
|
|
|
|
3-3 Female |
WsH |
HLA |
HLA |
HLA |
HLA |
|
|
|
|
|
|
|
|
|
|
|
|
|
0= No signs of systemic toxicity
H = Hunched posture
L = Lethargy
P = Pilo‑erection
A = Ataxia
Rd = Decreased respiratory rate
Rl = Labored respiration
Ws = Splayed gait
Wt = Tiptoe gait
To = Occasional body tremors
Dh = Dehydration
D = Diarrhea
Em = Emaciation
X = Animal dead
X* = Animal killed for humane reasons due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence
Individual Body Weights and Body Weight Changes -2000mg/kg
Dose Level mg/kg |
Animal Number and Sex |
Body Weight (g) at Day |
Body Weight (g) |
Body Weight Gain (g) During Week |
|||
0 |
7 |
14 |
1 |
2 |
|||
2000 |
2-0 Female |
171 |
158 |
169 |
|
-13 |
11 |
3-0 Female |
158 |
- |
- |
120 |
- |
- |
|
3-1 Female |
171 |
164 |
192 |
|
-7 |
28 |
|
3-2 Female |
163 |
- |
- |
134 |
- |
- |
|
3-3 Female |
155 |
- |
- |
135 |
- |
- |
-= Animal dead
Individual Necropsy Findings -2000 mg/kg
Dose Level |
Animal Number |
Time of Death |
Macroscopic Observations |
2000 |
2-0 Female |
Killed Day 14 |
No abnormalities detected |
3-0 Female |
Humanely killed Day 6 |
Liver: dark Kidneys: dark Gastric mucosa: epithelial sloughing |
|
3-1 Female |
Killed Day 14 |
No abnormalities detected |
|
3-2 Female |
Found dead Day 4 |
Liver: dark Kidneys: dark |
|
3-3 Female |
Found dead Day 1 |
Liver: patchy pallor Stomach: solid substance present Non-glandular epithelium of the stomach: hemorrhage |
Individual Clinical Observations and Mortality Data -300mg/kg
Dose Level mg/kg |
Animal Number and Sex |
Effects Noted After Dosing |
Effects Noted During Period After Dosing |
||||||||||||||||
½ |
1 |
2 |
4 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
||
300 |
1-0 Female |
0 |
0 |
HL |
HLP |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
4-0 Female |
0 |
H |
H |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4-1 Female |
HWt |
HWt |
HWt |
H |
H |
H |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4-2 Female |
H |
HWt |
HWsL |
PrRdRl |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
4-3 Female |
0 |
H |
H |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4-4 Female |
H |
H |
H |
H |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0= No signs of systemic toxicity
H = Hunched posture
L = Lethargy
P = Pilo‑erection
Pr = Prostration
Ho = Hypothermia
Rd = Decreased respiratory rate
Rl = Labored respiration
Ws = Splayed gait
Wt = Tiptoe gait
X* = Animal killed for humane reasons due to the occurrence of clinical signs of toxicity that exceeded the severity limit set forth in the UK Home Office Project Licence
Individual Body Weights and Body Weight Changes -300mg/kg
Dose Level mg/kg |
Animal Number and Sex |
Body Weight (g) at Day |
Body Weight (g) |
Body Weight Gain (g) During Week |
|||
0 |
7 |
14 |
1 |
2 |
|||
300 |
1-0 Female |
167 |
183 |
196 |
|
16 |
13 |
4-0 Female |
157 |
171 |
183 |
|
14 |
12 |
|
4-1 Female |
178 |
200 |
218 |
|
22 |
18 |
|
4-2 Female |
178 |
- |
- |
164 |
- |
- |
|
4-3 Female |
167 |
190 |
199 |
|
23 |
9 |
|
4-4 Female |
175 |
195 |
211 |
|
20 |
16 |
-= Animal dead
Individual Necropsy Findings -300mg/kg
Dose Level |
Animal Number |
Time of Death |
Macroscopic Observations |
300 |
1-0 Female |
Killed Day 14 |
No abnormalities detected |
4-0 Female |
Killed Day 14 |
No abnormalities detected |
|
4-1 Female |
Killed Day 14 |
No abnormalities detected |
|
4-2 Female |
Humanely killed Day 0 |
Stomach: clear liquid present Non-glandular epithelium of the stomach: thickened |
|
4-3 Female |
Killed Day 14 |
No abnormalities detected |
|
4-4 Female |
Killed Day 14 |
No abnormalities detected |
Applicant's summary and conclusion
- Interpretation of results:
- other: Harmful
- Remarks:
- in accordance with EU CLP (EC no. 1272/2008 and its amendments)
- Conclusions:
- The acute oral LD50 for the substance in male and female rats was determined to be between 300 and 2000 mg/kg bw (and roughly estimated to be 1850).
- Executive summary:
The substance was tested in an acute oral toxicity test, using the fixed dose method (OECD TG 420) at doses of 2000 and 300 mg/kg bw. At 2000 mg/kg bw, mortality occurred in two out of five animals, while a third animal was killed for humane reasons due to severe clinical signs of toxicity. At 300 mg/kg bw, one animal was killed out of humane reasons due to severe clinical signs of toxicity. Clinical signs at 2000 mg/kg bw included hunched posture, lethargy, pilo-erection, decreased respiratory rate, labored respiration, splayed or tiptoe gait, occasional body tremors, ataxia, dehydration, diarrhea and emaciation. Macroscopy in animals that either died or were humanely killed during the study at 2000 mg/kg bw showed a dark liver or patchy pallor of the liver, dark kidneys, solid substance present in the stomach, epithelial sloughing of the gastric mucosa and hemorrhagic non-glandular epithelium of the stomach. At 300 mg/kg bw, clinical signs included hunched posture, lethargy, pilo-erection. For the animal that was humanely killed during the study, clinical signs included a decreased respiratory rate, labored respiration, splayed gait, prostration and hypothermia. Macroscopy in the animal that was humanely killed during the study at 300 mg/kg bw showed presence of a clear liquid or solid substance in the stomach and a thickened non-glandular epithelium. All surviving animals appeared normal at the end of the study and no abnormalities were noted for these animals during macroscopy. The acute oral LD50 resulted in 300 -2000 mg/kg bw and is roughly estimated to be 1850 mg/kg bw.
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