Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
80.54 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
6.25
Dose descriptor starting point:
NOAEC
Modified dose descriptor starting point:
NOAEC
Value:
503.38 mg/m³
Explanation for the modification of the dose descriptor starting point:

See "justification and comments", below.

AF for dose response relationship:
1
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is usually not applied in the derivation of the inhalation DNEL. In this case, differences in the allometry are assumed to be compensated by differences in the respiration rate.
AF for other interspecies differences:
1.2
Justification:
Default factor of 2.5 has been reduced by half (to 1.25) to account for lower uptake in humans by comparison to rats
AF for intraspecies differences:
5
Justification:
To take into account intraspecies variations (between humans) for DNELs for workers, the assessment factor is 5 and for the general population it is 10.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 879.27 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
23 490.87 mg/m³
Explanation for the modification of the dose descriptor starting point:

See "justification and comments", below.

AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
95.47 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
Justification:
respiratory tract irritation local effects AF of 1 (Ecetoc TR110, 2010)
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
190.94 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
DNEL extrapolated from long term DNEL
Dose descriptor starting point:
NOAEC
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
Justification:
Irritation local effects AF of 1 (Ecetoc TR110, 2010)
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

Workers - 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The DNEL for long-term systemic effects by inhalation exposure was calculated on the basis of the developmental toxicity screening study, which was found to be the most sensitive endpoint from the available data. Short-term systemic effects were considered on the basis of a cardiac sensitisation study rather than the available acute toxicity data, on the basis that the cardiac effects were seen at lower levels and following very brief exposure to 2-bromo-3,3,3-trifluoropropene. Use of data obtained from the cardiac sensitisation test, by itself or in conjunction with PBPK modelling, for determination of acceptable acute exposures is consistent with industry guidance for fire extinguishing compounds as contained in standards such as NFPA 10, Standard on Portable Extinguishers, NFPA 2001, Standard on Clean Agent Fire Extinguishing Systems, and ISO 14520, Gaseous Fire-Extinguishing Systems.

Local effects following inhalation were calculated on the basis of apparent respiratory irritation seen even at relatively low levels in the 90-day repeat inhaled dose toxicity study; this was used as the starting point for derivation of the acute DNEL as well as long term, as signs of respiratory irritation were seen from the first exposure (therefore suggesting that the irritation may develop at this level, even over a short period of time such as a single exposure).

For the long-term systemic inhaled DNEL, the "remaining differences" assessment factor has been reduced by a factor of 2 (i.e. reduced from the default value of 2.5 to 1.25) on the basis that uptake into the bloodstream is anticipated to be lower in humans than in rats. The blood:air partition coefficient in rats was found to be 0.52 (Huntingdon Life Sciences study WAG0015, 2012) whereas the blood:air coefficient in humans was found to be 0.21 (Battelle, Pacific Northwest Division, 2013). Note that this correction was not also applied to the short-term systemic inhaled DNEL, because for the short-term effect the starting point was taken from a cardiac sensitisation study in dogs; in the absence of suitable data concerning the blood:air partition coefficient in dogs, the default factor is used.

It was not possible to conduct some dermal studies for the substance on the basis that the boiling point was very low and the concentration of test material in contact with skin could not be maintained for long enough to adequately conduct tests for skin sensitisation or dermal toxicity. It is anticipated that any incidental skin contact which could occur during handling of the material would be limited by rapid evaporation, and as such acute skin contact was not considered to present a hazard. Long-term skin contact (i.e. from repeated occasional skin contact ) was considered on a purely precautionary basis and the DNEL derived from the same starting point as the long-term inhalation DNEL. The substance was found not to cause irritation by skin or eye contact; in the absence of skin sensitisation data or any other information regarding local effects it is considered that the substance does not present a hazard of local effects by skin contact.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
67 975 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
Explanation for the modification of the dose descriptor starting point:

See the explanation of hazard conclusion below

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

Use of 2-bromo-3,3,3-trifluoropropene will be limited to the end use of fire extinguishers containing the substance. This is expected to be an infrequent event and so long-term exposure of the public is not considered. The anticipated exposure pattern involves a single brief exposure by inhalation for up to five minutes, after which time it is expected that the user would have withdrawn from the area of operation and / or the area should have been adequately ventilated as to remove any residual extinguishing agent. It should be noted that under the anticipated conditions of use there may be a significant concentration of airborne contaminants (i.e. combustion products) and so removal of unprotected individuals from the affected area will be a priority.

On the basis that no routine exposure is anticipated and that end-user exposure will be brief and relatively rare, risk related to long-term exposure are not considered. The risk of harm to the general population by dermal contact with the substance is not considered because the end use of fire extinguishers involves the release of the substance as a liquid which rapidly evaporates; no significant skin contact is expected.

It is noted that although some study results suggest that 2-bromo-3,3,3-trifluoropropene may cause irritation to the respiratory tract, even when exposure is limited to 5 minutes (note clinical signs seen in the 10,000 ppm exposure group of 2014 reproductive toxicity screen), however these were relatively minor (limited to salivation and / or red or clear discharge around the mouth or nose of the exposed animals) and recovered within 1 hour of the end of exposure. It is also noted that in the event of a fire (i.e. the conditions under which fire extinguisher end use would be necessary) there are likely to be significant concentrations airborne combustion products which may cause respiratory irritation therefore respiratory irritation could not be considered specific to the agent used to extinguish the fire.

The hazard for acute systemic effects is based on Physiologically Based Pharmacokinetic Modelling, as stated in Appendix 2 Section 35 of The US Federation Aviation Administration Advisory Circular (AC) 20 -42D-2011 (01 -14 -11), using measured arterial blood level concentrations at the LOAEL for cardiac sensitisation, which is considered the most sensitive endpoint for short-term exposure. Refer to the attached document (Colton and Poet, 2013) for further detail. Several studies involving human exposure in a laboratory setting  establish the potential significance for human health of animal data on  cardiac sensitization. Evaluating the safety of potential halon  substitutes requires the measurement of the No Observed Adverse Effect  Level (NOAEL) and the Lowest Observed Adverse Effect Level (LOAEL) of  cardiac sensitization in an appropriate species, usually the dog. EPA  uses the NOAEL value as the basis to ensure protection of the worker  population. The protocols used to determine the cardiotoxic NOAEL and  LOAEL concentrations for each agent are conservative. The  cardiotoxicity effect levels are measured in animals that have been  made more sensitive to these effects by the administration of  epinephrine concentrations which are just below the concentrations at  which epinephrine alone causes cardiotoxicity. The concentration of  epinephrine required to cause this heightened sensitivity is  approximately ten times greater than the concentration a human being  would be likely to secrete under stress (US EPA Publication of the First Significant New Alternatives Policy (SNAP) Program rule, in the US Federal Register 1994).