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EC number: - | 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
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- Oxidation reduction potential
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- Endpoint summary
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- Environmental data
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- 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
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- Toxicological Summary
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- Specific investigations
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- 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:
- 1.06 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):
- 25
- Dose descriptor starting point:
- NOAEL
- Value:
- 1.06 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 1.06 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Corrected inhalatory NOAEC from oral NOAEL: Oral NOAEL x (1/sRVrat) x (ABSoral-rat/ABSinh-human) x (sRVhuman/wRV); 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); Corrected NOAEC = 30 mg/kg/day x (1/0.38 m3/kg/day) x (0.5) x 6.7 m3/10m3 = 26.4474 mg/m³. Applying the remaining assessment factors of 25, the long-term systemic inhalation DNEL = 1.06 mg/m³.
- AF for dose response relationship:
- 1
- Justification:
- The most sensitive NOAEL was 30 mg/kg/day in males, based on a subchronic study in rats (OECD 408). The dose response relationship is considered unremarkable. therefore, no additional factor is used.
- AF for differences in duration of exposure:
- 2
- Justification:
- REACH Guidance: The assessment factors for exposure durations of subchronic to chronic is 2.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- REACH Guidance not applicable when setting an inhalatin DNEL. Respiratory intraspecies differences are fully covered by the factors used for route to route extrapolation.
- AF for other interspecies differences:
- 2.5
- Justification:
- REACH Guidance
- AF for intraspecies differences:
- 5
- Justification:
- REACH Guidance
- AF for the quality of the whole database:
- 1
- Justification:
- REACH Guidance
- AF for remaining uncertainties:
- 1
- Justification:
- 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:
- 1.2 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):
- 100
- Dose descriptor starting point:
- NOAEL
- Value:
- 1.2 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1.2 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Based on the phys-chem properties (low water solubility, higher logKow) and the lack of skin (and eye) irritating property, the dermal absorption was estimated to be 25% of oral. Thus, the oral NOAEL of 30 mg/kg bw/d was converted to the modified dose descriptior starting point of 120 mg/kg bw/d.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 2
- Justification:
- Based on REACH Guidance: REACH Guidance: The assessment factors for exposure durations of subchronic to chronic is two.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Based on 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:
- medium hazard (no threshold derived)
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
MW |
Water Solubility |
Log P |
Vapor Pressure |
Skin irritation |
Systemic Toxicity |
Average: 273 (range: 264 -306) |
19.6 mg/L @ 20oC |
6 @ 20oC |
66 Pa @ 25oC |
No |
Yes, oral; OECD 408 study; |
DNEL Discussion
An oral repeat dose study (OECD 408) in rats was used. The oral (gavage) administration of 1,2,4,5,7,8-Hexoxonane, 3,6,9-trimethyl-, 3,6,9-tris(Ethyl and Propyl) derivatives (CAS No. 1613243-54-1) for ninety consecutive days, to Wistar rats of both sexes, at dose levels of 10, 30 or 120 mg/kg bw/day resulted in adverse liver changes in males treated with 120 mg/kg bw/day, non-adverse kidney changes (hyaline droplets) in males treated with 120 mg/kg bw/day and adaptive liver changes in females treated with 120 mg/kg bw/day. The hyaline droptlets formation in male rats is a known species-specific and gender restricted phonomenon and is not considered relevant for human health assessment. Adverse changes in the liver of males were as follows: Bile duct hyperplasia was present in five males treated with 120 mg/kg bw/day with associated inflammatory cell infiltration evident in three of these males. Pigment deposits were also present in the bile ducts of seven males treated with 120 mg/kg bw/day. Following the treatment-free period, bile duct hyperplasia persisted, albeit at a lower incidence and at minimal severity in two males previously treated with 120 mg/kg bw/day and pigment deposits in the bile ducts was evident in five males previously treated with 120 mg/kg bw/day. Pigment was apparent in the bile ducts of one female previously treated with 120 mg/kg bw/day. Centrilobular hypertrophy was evident in five males and seven females treated with 120 mg/kg bw/day. Recovery was complete following the treatment-free period. No treatment-related effects were evident in animals of either sex treated with 30 or 10 mg/kg bw/day. The ‘No Observed Effect Level’ (NOEL) for systemic toxicity was therefore considered to be 30 mg/kg bw/day for both sexes. The No Observed Adverse Effect Level (NOAEL) for males was also considered to be 30 mg/kg bw/day.This was considered to be the most sensitive and conservative NOAEL and therefore was used for DNEL derivation. Hypertrophy in the liver of females treated with 120 mg/kg bw/day was considered to represent an adaptive response to treatment, therefore, a NOAEL for females was considered to be 120 mg/kg bw/day. Following the treatment-free period, complete recovery in the kidney changes and adaptive liver changes (centrilobular hypertrophy) were evident in recovery animals and the adverse liver changes (bile duct hyperplasia and pigment deposits) were evident at lower incidence and severity.
In a previous OECD 422 study in rats, oral administration of CAS#1613243 -54 -1 to rats by gavage, at dose levels of 50, 150 and 500 mg/kg bw/day, resulted in treatment related effects in animals of either sex from all treatment groups. A ‘No Observed Effect Level’ (NOEL) for systemic toxicity was therefore not established for either sex. Hypertrophy in the liver of females treated with 50 mg/kg bw/day was considered to represent an adaptive response to treatment; therefore a No Observed Adverse Effect Level for females was considered to be 50 mg/kg bw/day. The microscopic change evident in the heart of males from all treatment groups and the brown pigment in bile ducts, bile duct hyperplasia and peribilary inflammation in the liver of 50 mg/kg bw/day males were considered to represent an adverse effect of treatment. The Lowest Observed Adverse Effect Level (LOAEL) for males was therefore considered to be 50 mg/kg bw/day. The ‘No Observed Effect Level’ (NOEL) for reproductive toxicity was considered to be 150 mg/kg bw/day based on reduced offspring viability, offspring body weight gain, litter size and litter weights on Days 1 and 4 post partum at 500 mg/kg bw/day. Conclusion: LOAEL of 50mg/kg/day for males was established as the most sensitive endpoint. It should be noted that the NOAEL for pregnant females was 50 mg/kg bw/d, which is close to the most recent NOAEL from the subchronic study above.And, the microscopic effects seen in myocardial tissue of males was totally absent in the recent OECD 408 study [performed by the same laboratory, same strain of rat etc].
Long term, systemic DNEL for occupational exposures to the test substance may occur mainly by dermal route, but may also occur by inhalation route. Therefore two long term DNELs were derived for Workers. However, as described elsewhere also, the substance is a skin sensitizer, whose risk is assessed qualitatively. The references used for all these approaches are from: (1). ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: characterization of dose [concentration] response for human health. Version 2. ECHA-2010 -G-19 -EN; (2) ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.7.12: Endpoint specific guidance: Guidance on toxicokinetics. May 2008; (3) ECHA (2012). Practical guide 15: How to undertake a qualitative human health assesmentand documnet it in a chemical safety report. November 2012.
Worker Inhalation Systemic DNEL:
Corrected inhalatory NOAEC from oral LOAEL
Oral LOAEL x (1/sRVrat) x (ABSoral-rat/ABSinh-human) x (sRVhuman/wRV)
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)
(ABS: absorption; sRV: standard respiratory volume; wRV: worker respiratory volume)
Corrected NOAEC = 30 mg/kg/day x (1/0.38 m3/kg/day) x (0.5) x 6.7 m3/10m3
= 26.4474 mg/m3
Applying remaining assessment factors (to the above dose descriptor) in accordance with Endpoint Specific Guidance Chapter 8:
Correction for interspecies differences: 2.5
26.4474 mg/m3/2.5 = 10.579 mg/m3
Correction for intraspecies differences: 5
10.579 mg/m3/5 = 2.1157 mg/m3
Correction for duration between subchronic to chronic: 2
2.1157 mg/m3/2 = 1.0579 mg/m3
Correction for dose-response: 1
1.0579 mg/m3/1 = 1.0579 mg/m3
Correction for whole database: 1 due to quality of study
1.0579 mg/m3/1 = 1.0579 mg/m3
Total AF = 25
Conclusion: DNEL inhalation-systemic-worker = 1.06 mg/m3
Worker Dermal Systemic DNEL:
Oral absorption rat – oral/dermal absorption human: Assume 25% absorption based on the phys-chem properties of low water solubility and higher logKow, and the lack of skin (and eye) irritating properties in
accordance with Endpoint Specific Guidance Chapter 8 and 7c (R.7.12). however, a qualitative approach is used to assess and control risks from dermal exposure (Guidance on information requirements and chemical safety assessment, Part E).
30 mg/kg/day/0.25 = 120 mg/kg/day = dermal dose descriptor (NOAEL)
Applying assessment factors in accordance with Endpoint Specific Guidance Chapter 8:
1. Correction for interspecies differences (factor for allometric scaling, 4 [rat] x 2.5, additional factors = 10; 120 mg/kg/day/10 = 12 mg/kg/day
2. Correction for intraspecies difference: 5; 12 mg/kg/day/5 = 2.4 mg/kg/day
3. Correction for duration between subchronic to chronic: 2; 2.4 mg/kg/day/2 = 1.2 mg/kg/day
4. Correction for dose-response: 1 (unremakable): 1; 1.2 mg/kg/day/1 = 1.2 mg/kg/day
5. Correction for whole database: 1 due to quality of study; 1.2 mg/kg/day/1 = 1.2 mg/kg/day
Total AF = 100
Conclusion: DNEL dermal-worker-systemic = 1.2 mg/kg/day
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
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