Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
120 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
Modified dose descriptor starting point:
NOAEC
DNEL value:
3 000 mg/m³
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:
13.9 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Short toxicity profile:

In acute studies 1,3-dioxepane exhibited no acute systemic toxicity relevant for classification (oral LD50 in rats 4523 mg/kg bw; inhalation LC50 >20.8 mg/l). No skin or respiratory tract irritation and no skin sensitizing potential was identified. Though mild eye irritation was observed in rats (resulting in classification according to Regulation 1272/2008/EG only).

In a 28-day oral study in Wistar rats (OECD Guideline 407) no treatment related effects were observed up to the highest dose tested (limit dose 1000 mg/kg bw/day).

In a subchronic inhalation toxicity study with rats no treatment-related, adverse effects were identified with exposure atmospheres of 3000 and 1000 mg/m3 (BASF SE, 2015). Though transient apathy, unsteady gait, salivation and nose and eye discharge were observed at the highest tested exposure atmosphere of 10000 mg/m3. In addition effects on clinical chemistry were described in the high exposure group resulting in a NOAEC of 3000 mg/m3.

No indications for a teratogenic effect of 1,3-dioxepane were described in an OECD 414 study in rats (BASF SE, 2015).

The derivation of DNELs was performed according to the ECHA Guidance on information requirements and chemical safety assessment - chapter R.8 (May 2008), partially adapted by justified variations.

 

Acute/short-term exposure – systemic effects – dermal DNEL

Not quantifiable; see above

 

Acute/short-term exposure – systemic effects – inhalation DNEL

Not quantifiable; see above

 

Acute/short-term exposure – local effects – dermal DNEL

Not quantifiable; see above

 

Acute/short-term exposure – local effects – inhalation DNEL

Not quantifiable; see above

 

Long-term exposure – systemic effects – dermal DNEL

Since no repeated dose study is available for the dermal route of exposure, a route-to-route extrapolation from the oral NOAEL is appropriate and is preferred to a route-to-route extrapolation from the inhalation NOAEC.No dermal penetration study is available but based on the physico-chemical properties of 1,3-dioxepane a lower dermal bioavailability compared to the oral route of exposure can be anticipated (see toxicokinetics). But in the absence of quantifiable data on differences in kinetics and metabolism of both, the starting route and the end route, the ECHA Guidance on information requirements and chemical safety assessment - chapter R.8, p.25 (May 2008) recommends worst case assumptions. Therefore in this context identical bioavailability was anticipated (i.e. factor 1) when performing oral-to-dermal extrapolation. Furthermore an additional factor for remaining differences was omitted and a factor of 3 was applied for interspecies differences, since in the available subacute oral study no treatment related effects were observed at the limit dose 1000 mg/kg bw/day.

 

NOAELrat, oral, systemic = NOAELrat, dermal, systemic = 1000 mg/kg bw

The assessment factor is the product of:

Subacute → chronic:                      6

Rat → human (allometric scaling):   4

remaining differences:                     1

Worker:                                         3

Quality of whole database:              1

Dose-response:                              1

DNELdermal, systemic, chronic:     13.9 mg/kg bw day

 

Long-term exposure – systemic effects – inhalation DNEL

A NOAEC of 3000 mg/m3 based on transient apathy, unsteady gait, salivation, nose and eye discharge and effects on clinical chemistry was identified in a subchronic toxicity study in rats (see above, BASF SE 2015).

 

The assessment factor is the product of:

Subchronic → chronic:                   2

Rat → human (allometric scaling):   1 (external dose)

remaining differences:                     2.5

Worker:                                         5

Quality of whole database:              1

Dose-response:                              1

DNELinhalation, systemic, chronic: 120 mg/m3

 

Long-term exposure – local effects – dermal DNEL

Not quantifiable; see above

 

Long-term exposure – local effects – inhalation DNEL

Not quantifiable; see above. Covered by Long-term exposure – systemic effects – inhalation DNEL.

 

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

Since only industrial uses of 1,3-dioxepane are supported by the CSA, no DNELs for the general population need to be derived.