Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
61 279 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
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:
no data available: testing technically not feasible
Acute/short term exposure
Hazard assessment conclusion:
no data available: testing technically not feasible
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no data available: testing technically not feasible
Acute/short term exposure
Hazard assessment conclusion:
no data available: testing technically not feasible

Workers - Hazard for the eyes

Additional information - 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 1,1,1,2,3,3,3 -heptafluoropropane (HFC 227ea) 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 subchronic (13 weeks/90 days) study with rats are available. No effects were observed at the highest dose tested (NOAEC of 731690 mg/m3). In two available developmental toxicity studies with rats and rabbits also no adverse effects were observed resulting in a NOAEL of 731690 mg/m3 (the highest dose tested).

In this hazard evaluation, the primary study to be used to determine the chemical’s hazard is the 90-day inhalation study with rats (WIL Research Laboratories, 1993).

As no local effects were observed in the available studies, no DNEL for local effects was derived.

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

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL:731690 mg/m3

The highest dose concentration in the subchronic toxicity study with rats; no adverse effects 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 was used, as available toxicokinetic studies indicated no metabolic differences between rats and humans.

Intraspecies

3

As no effects were observed at the highest tested concentration (50000 ppm v/v), an intraspecies AF of 3 is considered as amply sufficient.

Exposure duration

2

A default assessment factor for difference in exposure duration, as proposed in the REACH Guidance (R. 8.4.3.1)

Dose response

1

 

Quality of database

1

 

DNEL

Value

For workers

731690 x 6/8 x 6.7/10 / (1 x 3 x 2 x 1 x 1) = 61279 mg/m3

 

The obtained value of 61279 mg/mg3 corresponds to the concentration of about 8813 ppm. This value is over 8 times higher than the TLV for inert gases (1000 ppm) established by ACGIH, indicating that the substance presents extremely low toxicological concern.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6 533 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
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:
no data available: testing technically not feasible
Acute/short term exposure
Hazard assessment conclusion:
no data available: testing technically not feasible
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no data available: testing technically not feasible
Acute/short term exposure
Hazard assessment conclusion:
no data available: testing technically not feasible

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no data available: testing technically not feasible
Acute/short term exposure
Hazard assessment conclusion:
no data available: testing technically not feasible
DNEL related information

General Population - Hazard for the eyes

Additional information - 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.

 

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 subchronic (13 weeks/90 days) study with rats are available. No effects were observed at the highest dose tested (NOAEC of 731690 mg/m3). In two available developmental toxicity studies with rats and rabbits also no adverse effects were observed resulting in a NOAEL of 731690 mg/m3 (the highest dose tested).

In this hazard evaluation, the primary study to be used to determine the chemical’s hazard is a 90-day inhalation study with rats (WIL Research Laboratories, 1993).

As no local effects were observed in the available studies, no DNEL for local effects was derived.

 

The DNEL for long-term exposure - systemic effects for consumers is derived as follows:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 731690 mg/m3

The highest concentration tested in the subchronic toxicity study with rats; no adverse effects observed

Step 2) Modification of starting point

6/24

5/7

Correction of exposure duration in study (6 hrs/day) to default general population exposure (24 hrs/day)[1].

5/7 was considered to address the different exposure conditions (5 days/week in the subchronic study, 7 days/week of exposure for general population)

Step 3) Assessment factors

 

 

Interspecies

1

No additional interspecies factor was used, as available toxicokinetic studies indicated no metabolic differences between rats and humans.

Intraspecies

10

As the general population includes the elderly and juvenile citizens, which are considered to be more sensitive, a default assessment factor of 10 is proposed in the REACH Guidance (R.8.4.3.1).

Exposure duration

2

A default assessment factor for difference in exposure duration, as proposed in the REACH Guidance (R. 8.4.3.1)

Dose response

1

 

Quality of database

1

 

DNEL

Value

For general population

731690 x (6/24) x (5/7) / (1 x 10 x 2 x 1 x 1) = 6533 mg/m3

[1] Exposure duration for humans indirect exposed via the environment is assumed 24 hours per day, 7 days week. For consumers the exposure duration is assumed 1-24 hours per day (depending on the exposure scenario).

The obtained value corresponds to 940 ppm.