Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
38 800 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Since the substance is a gas with a boiling point of -47.4 deg C, the only relevant route of exposure is by inhalation. The DNELacute only needs to be derived in the case where the substance is labelled for acute toxicty hazard and when peak exposures substantially higher than the DNELlong-term are possible. As it is not classified as an acute toxiciy hazard, it does not require a DNELacute. As 1,1,1 -trifluoroethane is not irritating, carcinogenic, mutagenic or toxic to reproduction or development, these endpoint do not need to be considered in deriving a DNEL. Therefore only a DNELlong-term for general toxic effects in the worker population is required.

The Workplace Environmental Exoposure Level Committee of the American Industrial Hygiene Association (WEEL) has reviewed the toxicology data on this substance and determined that the appropriate occupational exposure level for this substance is 1000 ppm as an 8-hr Time-Weighted-Average. This is based on the studies that have shown that the LC50 > 540,000 ppm in rats. In dogs, a cardiac sensitization response to adrenalin was observed only at 300,000 ppm. In repeat inhalation toxicity and developmental toxicity studies the NOEL was 40,000 ppm, the highest level tested.

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 1,1,1 -trifluoroethane is a gas, oral and dermal routes of exposure are considered to be irrelevant, therefore no DNELs were derived for these routes.

 

As the substance is not classified for acute toxicity, according to the REACH “Guidance on information requirements and chemical safety assessment” (R.8.4.3.1), no acute / short-term exposure DNELs need to be derived.

 

For long-term exposure, data from a 90 day repeated dose toxicity study is available. In this study, no adverse effects were observed in rats at the high concentration tested (NOAEC of 214000 mg/m3, corresponding to a target limit concentration of 40000 ppm). This value will be used to derive a DNEL for long-term exposure. The substance is not genotoxic, not carcinogenic, and is not a reproductive or developmental toxicant. Therefore, no DNELs will be derived for these endpoints,i.e., the long-term DNEL is also considered sufficient to protect against these effects.

 

The DNEL for long-term exposure - local/systemic effects for workers is derived as follows:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC:214000 mg/m3

The highest concentration in the subacute toxicity study with rats; no adverse effects were observed.

Step 2) Modification of starting point

6/8

 

 

6.7 m3/10 m3

Correction of exposure duration in study (6 hrs/day, 5 days/week) to default worker exposure (8 hrs/day, 5 days/week);

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

Step 3) Assessment factors

 

 

Interspecies

1

No additional interspecies factor is applied as:

- regarding toxicokinetics: no metabolic differences between rats and humans are expected for HFC-143a based on the substance chemical inertness and rapid excretion in unmetabolised form;

- regarding toxicodynamics: no effects were observed up to the relatively very high concentration of 214000 mg/m3. In addition, no differences are expected based on the chemical inertness of HFC-143a.

Intraspecies

3

HFC-143a can be considered as chemically and biologically inert, without expected toxicological properties. An assessment factor of 3 is considered sufficient to account for the intraspecies differences in the worker population

Exposure duration

1

No assessment factor for duration extrapolation (subacute to chronic) is applied as no adverse effects were observed in the subacute study at the very high tested concentration. Furthermore, the available toxicokinetic data shows that the substance is rapidly excreted and does not accumulate. Therefore it is not expected that adverse effects will occur at lower concentrations after chronic exposure and the use of an assessment factor is considered to be unnecessary.

Dose response

1

 

Quality of database

1

 

DNEL

Value

For workers

214000 x 6/8 x 6.7/10 / (1 x 3 x 1 x 1 x 1) = 38800 mg/m3(10400 ppm)

 

The DNEL of 38800 mg/m3corresponds to the concentration of 10400 ppm. This value is more than a factor 10 higher than the TLV for inert gases (1000 ppm) established by the ACGIH, indicating that the substance presents an extremely low toxicological concern.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 700 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Exposures for 6-hr/day, 5 days/wk for 13 weeks at levels up to 40,000 ppm did not result in any systemic effects.