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EC number: 455-560-2 | CAS number: -
- 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
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.76 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 132.24 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The systemic NOAEL of 150 mg/kg/day from a 28 -day repeat dose oral study with rats was used. Assuming an oral /inhalation
absorption of 0.5 a dose descriptor of 132.26 mg/m3 was derived as the starting point. This study was was used for DNEL derivation as it is the only repeated dose study and the study is of good quality (GLP, OECD guideline).
- AF for dose response relationship:
- 1
- Justification:
- based on REACH guidance
- AF for differences in duration of exposure:
- 6
- Justification:
- based on REACH guidance: subacute to chronic
- Justification:
- Not applicable for inhalation DNEL, per REACH guidance
- AF for other interspecies differences:
- 2.5
- Justification:
- based on REACH guidance
- AF for intraspecies differences:
- 5
- Justification:
- based on REACH guidance
- AF for the quality of the whole database:
- 1
- Justification:
- based on REACH guidance
- AF for remaining uncertainties:
- 1
- Justification:
- based on REACH guidance
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 300
- Dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The systemic NOAEL of 150 mg/kg/day from a 28 -day repeat dose oral study in rats was used. Assuming a dermal absorption of 50% a dose descriptor of 300 mg/kg/day was derived as the starting point.This study was was used for DNEL derivation as it is the only repeated dose study and as it is a study of good quality (GLP, OECD guideline).
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Route of original study:
- Dermal
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
DNEL Calculations for 3,3,5,7,7-pentamethyl-1,2,4-trioxepane
WS |
g/L, in water (measured) |
5.54 at 20.1oC |
Log Pow |
(OECD 117) |
2.4 at 22oC |
VP |
Pa (measured) |
274 at 20oC |
Skin/eye irritation |
(measured) |
Non irritant |
Skin sensitization |
|
Non-sensitizer |
NOAEL, oral, rat |
Mg/kg bw/day |
150 |
Although the oral LD50 is 300 - 2000 mg/kg and classified for acute toxicity (Cat 4), the LD50 for dermal and inhalation routes are high and are not classified. The latter route-specific data were not appropriate to calculate short term Worker DNELs. Hydrophilic substances, by dissolving in the mucus lining of the respiratory tract are effectively removed from the air in the upper respiratory tract. Occupational exposure, if any, may only be by dermal or inhalation exposures. Therefore two long-term DNELs are calculated for workers - inhalation and dermal.
.
The OECD TG 407 study is selected for DNEL derivation as it is the only repeated dose study available and is a study of good quality (GLP, OECD guideline). The following treatment related microscopic findings were observed: (1) Bile duct proliferation of minimal or slight degree (2/5 males and 2/5 females at 150 mg/kg/day, 4/5 males and 4/5 females at 450 mg/kg/day); (2) Diffuse midzonal/centrilobular hypertrophy of the liver at minimal or slight degree (4/5 males at 450 mg/kg/day); (3) Increased severity of cortical hyaline droplets in the kidneys to slight or moderate degree (4/5 males at 150 mg/kg/day and 5/5/ males at 450 mg/kg/day); (4) Very slight increase in the severity of splenic hemopoiesis (primarily erythropoiesis) to a moderate degree (1/5 males at 450 mg/kg/day). The bile duct effects observed at 150 mg/kg/day were not indicative of clear organ dysfunction and were not regarded to be adverse in toxicological terms. Reduced red blood cell counts, hemoglobin level, and hematocrit level in females at 150 and 450 mg/kg/day were seen, but reticulocytosis was seen only at the high dose. Liver weight of males and females at 450 mg/kg/day were increased, while liver to body weight ratios were increased in males and females at 150 and 450 mg/kg/day. There were no increases in the enzymes indicative of liver pathology. The liver changes were considered as typical adaptive changes to xenobiotics. A slightly increased kidney to body weight ratio was measured for males at 450 mg/kg/day. The kidney microscopic observation (hyaline droplets formation) is a well-known species (rat) and gender (male) specific finding with certain chemicals. This finding, although adverse in male rats, is irrelevant for human hazard assessment. Deaths at 450 mg/kg/day were considered treatment-related, and as such considered to be clear evidence for an adverse effect of the test substance at this dose level. Therefore, from the results presented in this report, a definitive systemic No Observed Adverse Effect Level (NOAEL) for Pentamethyl-trioxepane of 150 mg/kg/day was established.
DNEL inhalation-systemic-workerfor 3,3,5,7,7-pentamethyl-1,2,4-trioxepane:
Corrected inhalatoary NOAEC: Oral NOAEL x (1/sRVrat) x (ABSoral-rat/ABSinh-human) x (sRVhuman/wRV)
Correction for inhalation and oral absorption rates: Assume ABSoral-rat/ABSinh-human is 50/100 = 0.5 based on phys-chem properties and Endpoint Specific Guidance chapters 8 and 7c (R.7.12).
Conversion into an inhalatory rat NOAEC: dividing by 0.38 m3/kg (8-hour respiratory volume in the rat)
Correction for activity driven differences in respiratory volume in workers compared to individuals at rest: (6.7 m3/10 m3) [ABS: absorption; sRV: standard Respiratory Volume; wRV: worker Respiratory Volume]
Corrected NOAEC = 150 mg/kg/day x (1/0.38 m3/kg/day) x (0.5) x 6.7 m3/10m3 = 132.24 mg/m3 (Dose descriptor)
Applying remaining assessment factors in accordance with Endpoint Specific Guidance Chapter 8:
Correction for interspecies differences: 2.5
132.24 mg/m3/2.5 = 52.9 mg/m3
Correction for intraspecies differences:5
52.9 mg/m3 /5 = 10.58 mg/m3
Correction for duration between subacute to chronic: 6
10.58 mg/m3/6 = 1.76 mg/m3
Correction for dose-response:1
1.76 mg/m3/1 = 1.76 mg/m3
Correction for whole database: 1 due to quality of study
1.76 mg/m3/1 = 1.76 mg/m3
Total AF = 75
1.76 mg/m3, DNEL inhalation-systemic-worker
DNEL dermal-systemic-workerfor 3,3,5,7,7-pentamethyl-1,2,4-trioxepane:
Correction for dermal and oral absorption rates of 3,3,5,7,7-pentamethyl-1,2,4-trioxepane (based on Guidance on information requirements and chemical safety assessment, Chapter R 7.12): Dermal absorption is assumed to be low for several reasons. 1. highly soluble in water (5.54 g/L); and 2. the experimental log Kow is 2.4. Most importantly, the substance is not a skin irritant, and a non-sensitizer to the skin. Therefore, low skin absorption is expected based on these biological behaviors and may be reasonably assumed to be 50% (correction factor= 0.5). No data is available on absorption by oral route. It is therefore assumed that oral absorption factor is 100 %.
Oral NOAEL (150 mg/kg/day) / 0.5 = 300 mg/kg/day = dermal dose descriptor.
Applying assessment factors in accordance with Endpoint Specific Guidance Chapters 8 and 7.c:
Correction for interspecies differences (apply factor for allometric scaling 4 for rat x 2.5 for additional factors): 10
300 mg/kg/day/10 = 30 mg/kg/d
Correction for intraspecies difference: 5
30 mg/kg/day/5 = 6 mg/kg/d
Correction for duration between sub-acute to chronic: 6
6 mg/kg/day/6 = 1 mg/kg/d
Correction for dose-response: 1 due to NOAEL
6 mg/kg/day/1 = 6 mg/kg/d
Correction for whole database: 1 due to quality of study
6 mg/kg/day/1 = 6 mg/kg/d
Total AF = 300
1 mg/kg/day, DNEL Dermal-worker-systemic
General population is not exposed to the substance by inhalation, dermal or oral exposure. The discharge of the substance in the environment (water, air) is extremely low. Therefore no inhalation and no dermal DNEL is derived for general population.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
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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