Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.4 mg/m³
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
LOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Workers

According to the REACH "Guidance on information requirements and chemical safety assessment" , a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. As the substance is a gas, oral and dermal routes of exposure are considered to be irrelevant, therefore no DNELs were derived for these routes. The substance is not classified for acute toxicity, and according to REACH "Guidance on information requirements and chemical safety assessment" (R.8.4.3.1), no acute/short term exposure DNELs need to be derived.

No NOAEL could be derived for carcinogenic effects in the 2 year NTP study in rats and mice since tumours were observed at the lowest level of exposure for rats, 156 ppm (638 mg/m3). Whilst TFE is carcinogenic in both mice and rats, there is no evidence that it has genotoxic properties. It is concluded, therefore, that the effects are due to a non-genotoxic mechanism and that risk characterisation can proceed using a DNEL based on the assumption of a threshold mechanism.

A DNEL for TFE can be derived using the LOAEL of 156 ppm (638 mg/m3) for renal tubular degeneration in the rat as the starting point and using the default approach proposed in the ECHA Guidance.

Table A. Calculation of DNEL for long-term exposure - carcinogenic / systemic effects in workers is derived as follows:

 Description  Value  Remark
  Relevant dose descriptor  Corrected LOAEL 320 mg/m3 (78 ppm) Correct for respiratory volume (from resting rat to active human): 6.7 m3/10m3 = 0.67. Correct for exposure time (from 6 hour rat to 8 hour human): 6/8 = 0.75 Corrected LOAEL = 638 x 0.67 x 0.75 = 320 mg/m3 (78 ppm)
Route to route extrapolation  1  Inhalation to inhalation
Scaling factor animal to man  1  No allometric scaling per REACH R.8.4.3.1
 Other interspecies differences  1 Mechanistic and comparative metabolism studies show that humans likely to be less sensitive to the effects of TFE than rats and mice and are unlikely to be more sensitive.
 Intraspecies variability  5  A default assesment factor for workers, as proposed in the REACH Guidance (R 8.4.3.1)
 Exposure duration  1  Chronic to chronic
 Dose response  5   No NOAEL
 Quality of the database  2  No developmental and limited reproductive data
 DNEL  Value  
For workers    320 / (1 x 1 x 1 x 5 x 1 x 5 x 2) = 6.4 mg/m3

DNEL for workers (based on ECHA Guidance = 6.4 mg/m3 (1.6 ppm)

The worker DNEL value derived for chronic exposure would have to be adapted in case of a different shift system (= daily exposure time). In that case the amended DNEL would result in virtually the same value under the condition that the weekly exposure time would be almost identical.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.59 mg/m³
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

General population

According to the REACH "Guidance on information requirements and chemical safety assessment" , a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. As the substance is a gas, oral and dermal routes of exposure are considered to be irrelevant, therefore no DNELs were derived for these routes. The substance is not classified for acute toxicity, and according to REACH "Guidance on information requirements and chemical safety assessment" (R.8.4.3.1), no acute/short term exposure DNELs need to be derived.

No NOAEL could be derived for carcinogenic effects in the 2 year NTP study in rats and mice since tumours were observed at the lowest level of exposure for rats, 156 ppm (638 mg/m3). Whilst TFE is carcinogenic in both mice and rats, there is no evidence that it has genotoxic properties. It is concluded, therefore, that the effects are due to a non-genotoxic mechanism and that risk characterisation can proceed using a DNEL based on the assumption of a threshold mechanism.

A DNEL for TFE can be derived using the LOAEL of 156 ppm (638 mg/m3) for renal tubular degeneration in the rat as the starting point and using the default approach proposed in the ECHA Guidance.

Table B. Calculation of DNEL for long-term exposure - carcinogenic / systemic effects in the general population is derived as follows:

 Description

 Value

 Remark

  Relevant dose descriptor

 Corrected LOAEL 159 mg/m3 (39 ppm)

Correct for exposure time (from 6 hour rat to 24 hour human): 6/24 = 0.25.

Corrected LOAEL = 638 x 0.25 = 159 mg/m3 (39 ppm)

Route to route extrapolation

 1

 Inhalation to inhalation

Scaling factor animal to man

 1

 No allometric scaling per REACH R.8.4.3.1

 Other interspecies differences

 1

Mechanistic and comparative metabolism studies show that humans likely to be less sensitive to the effects of TFE than rats and mice and are unlikely to be more sensitive.

 Intraspecies variability

 10

 A default assesment factor for the general population, as proposed in the REACH Guidance (R 8.4.3.1)

 Exposure duration

 1

 Chronic to chronic

 Dose response

 5

  No NOAEL

 Quality of the database

 2

 No developmental and limited reproductive data

 DNEL

 Value

 

For general population 

 

159 / (1 x 1 x 1 x 10 x 1 x 5 x 2) = 1.59 mg/m3

DNEL for general population (based on ECHA Guidance = 1.59 mg/m3 (0.39 ppm)