Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.8 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
Modified dose descriptor starting point:
NOAEC
Value:
44 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 = 50 mg/kg/day x (1/0.38 m3/kg/day) x (0.5) x 6.7 m3/10m3 = 44 mg/m3. Applying the remaining assessment factors of 25, the long-term systemic inhalation DNEL = 1.8 mg/m3.
AF for dose response relationship:
1
Justification:
REACH Guidance
AF for differences in duration of exposure:
2
Justification:
REACH Guidance
Justification:
REACH Guidance not applicable when setting an inhalatin DNEL
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:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal absorption was estimated to be 20% of oral.
AF for dose response relationship:
1
Justification:
Based on REACH Guidance
AF for differences in duration of exposure:
2
Justification:
Based on REACH Guidance
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:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

MW

Water Solubility

Log P

Vapor Pressure

Surface Tension

Systemic Toxicity

264

13.1 mg/L

(slightly soluble)

4.84

4.1 Pa (0.0041 KPa)

Log10 Koc 3.16

Yes 90-day oral

DNEL Discussion

1,2,4,5,7,8-Hexoxonane, 3,6,9-triethyl-3,6,9-trimethyl- CAS# 24748-23-0 is a cyclic peroxy ketone

Study: 90-day repeat dose oral

NOAEL: 50 mg/kg/day

Summary: Findings at 50 mg/kg/day were of a minimal nature and did not indicate an adverse effect on

functional integrity. Based on the findings in the liver, kidneys and blood at 150 and 450

mg/kg/day,a No Observed Adverse Effect Level (NOAEL) of 50 mg/kg/day

was established.

 

Worker Inhalation Systemic DNEL

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 = 50 mg/kg/day x (1/0.38 m3/kg/day) x (0.5) x 6.7 m3/10m3

= 44 mg/m3

 

Applying remaining assessment factors in accordance with Endpoint Specific Guidance Chapter 8:

 

Correction for interspecies differences: 2.5

44 mg/m3/2.5 = 17.6 mg/m3

Correction for intraspecies differences: 5

17.6 mg/m3/5 = 3.52 mg/m3

Correction for duration between subchronic to chronic: 2

3.53 mg/m3/2 = 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 = 25

1.8 mg/m3DNEL inhalation-systemic-worker

Worker Dermal Systemic DNEL

Oral absorption rat – oral/dermal absorption human: Assume 20% absorption based on the phys-chem data in accordance with Endpoint Specific Guidance Chapter 8 and 7c (R.7.12).

 

50 mg/kg/day/0.2 = 250 mg/kg/day = dermal dose descriptor

 

Applying assessment factors in accordance with Endpoint Specific Guidance Chapter 8:

 

Correction for interspecies differences (apply factor for allometric scaling 4 for rat x 2.5 for additional factors): 10

250 mg/kg/day/10 = 25 mg/kg/day

Correction for intraspecies difference: 5

25 mg/kg/day/5 = 5 mg/kg/day

Correction for duration between sub-chronic to chronic: 2

5 mg/kg/day/2 = 2.5 mg/kg/day

Correction for dose-response: 1 due to NOAEL

2.5mg/kg/day/1 = 2.5

Correction for whole database: 1 due to quality of study

2.5 mg/kg/day/1 = 2.5 mg/kg/day

Total AF = 100

2.5 mg/kg/day DNEL dermal-worker-systemic

 

 

 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population