Registration Dossier

Administrative data

Description of key information

In vivo tests are reported. The results show that HCFC 122a is a low-toxic compound following oral and inhalation expsoure. No toxicity was observed following dermal exposure.
According to Regulation (EU) 1272/2008, HCFC 122a does not fulfill the classification criteria for the Acute Toxicity hazard classes.

Following exposure by inhalation or oral routes, clinical signs included symptoms of damage to the nervous system: short period of agitation followed by lethargy, drowsiness, muscle twitching and narcosis.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The data source is the competent authority, it is considered reliable. Although details on test method and results are not completely described, the results are sufficient to aim
Reason / purpose for cross-reference:
reference to same study
Principles of method if other than guideline:
Test was conducted on white mice and rats at dose from 3 to 15 g/kg.
During the acute experiment dynamic monitoring of the clinical signs was carried out and the weight of animals was measured.
GLP compliance:
not specified
Test type:
other: not reported
Limit test:
no
Species:
other: rat and mouse
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
from 3 to 15 g/kg
No. of animals per sex per dose:
not reported
Control animals:
not specified
Sex:
not specified
Dose descriptor:
approximate LD50
Effect level:
8 680 mg/kg bw
Interpretation of results:
GHS criteria not met
Conclusions:
HCFC 122a is a low-toxic compound, experimental results were very closed to the predicted LD50 value of 8680 mg/kg.
Executive summary:

The objective of the reported study was to investigate the toxicity of HFCF 122a and HCFC 132 and to characterize their biological action in order to validate the approximate safe level of these compounds in the air of working area, ambient air, and water. In this study both a review of the available toxicological data on similar chemical compounds was made and toxicological tests on HFCF 122a and HCFC 132 were performed.

 

The acute toxicity levels of the HCFC 122a were both calculated and experimentally determined.

 

In order to obtain approximate data on the acute toxicity of the HCFC 122a and HCFC 132, the following equation, derived basing on experimental data on similar compounds, was applied:

log LD50(mmol/kg) = 1.25 – 1.54 · tb· 10-2+ 0.63 · log Pow

where:

tb= boiling point

Pow = partition coefficient octanol/water

 

The calculated value of LD50for HCFC 122a is reported to be 8680 mg/kg b.w.

Following the calculation of the approximated LD50, experimental studies of oral acute toxicity were conducted on white mice and rats at dose from 3 to 15 g/kg.

During the acute experiment dynamic monitoring of the clinical sign was carried out and the weight of animals was measured.

Results show that HCFC 122a is a low-toxic compound, since the experimental results were very closed to the predicted toxicity parameters.

Clinical signs in animals predominantly consisted of symptoms of nervous system damage. Acute poisoning within the first hours was accompanied by excitation of animals, followed by depression, motor retardation, shortness of breath, muscle atonia. Death of laboratory animals was observed within the first 1-3 days of observations. No species-sensitivity was observed. HCFC 122a and HCFC 132 did not exhibit cumulative properties.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
7 800 mg/kg bw
Quality of whole database:
Although details on test method and results are not completely described in the quoted references, the results are sufficient to aim a conclusion for the health hazard assessment of the substance.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
The data source is the competent authority, it is considered reliable. . Although details on test method and results are not completely described, the results are sufficient to aim a conclusion for the health hazard assessment of the substance.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
no data
GLP compliance:
not specified
Test type:
other: no data
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Analytical verification of test atmosphere concentrations:
not specified
Remarks on duration:
no data
Concentrations:
from 5 to 100 mg/L
No. of animals per sex per dose:
no data
Control animals:
not specified
Sex:
male
Dose descriptor:
LC50
Effect level:
72 mg/L air
Based on:
act. ingr.
Sex:
male
Dose descriptor:
discriminating conc.
Remarks:
Test concentration causing evident toxicity but not mortaility
Effect level:
4 mg/L air
Based on:
act. ingr.

Indicators of state, results at the concentration of 2, 4, 6, 8, 10 mg/L.

 

Summation-threshold value

HCFC 122a

Concentrations

in 24 hours

in 48 hours

                      Control

5.2±0.4

5.0±0.35

2 mg/l

5.4 ± 0.3

5.1 ± 0.4

4 mg/l

6.6 ± 0.31

6.2 ± 0.6

6 mg/l

6.8 ± 0.4

6.7 ± 0.4

8 mg/l

6.9 ± 0.3

6.8 ± 0.3

10 mg/l

7.1 ± 0.4

7.0 ± 0.5

 

 “hole exploratory behaviour”

HCFC 122a

Concentrations

in 24 hours

in 48 hours

Control

12.1±1.4

11.6±1.3

2 mg/l

11.9 ± 1.1

11.3 ± 1.0

4 mg/l

8.9 ± 1.1

8.3 ± 0.9

6 mg/l

8.3 ± 1.2

8.1 ± 0.8

8 mg/l

7.1 ± 0.6

7.3 ± 0.6

10 mg/l

7.2 ± 0.5

6.8 ± 0.4

 

Erythrocyte count in peripheral blood

HCFC 122a

Concentrations

in 24 hours

in 48 hours

Control

6.86±0.3

6.67±0.29

2 mg/l

7.1 ± 0.4

6.9 ± 0.3

4 mg/l

6.9 ± 0.25

6.95 ± 0.29

6 mg/l

6.89 ± 0.23

7.0 ± 0.28

8 mg/l

6.83 ± 0.42

7.1 ± 0.3

10 mg/l

6.9 ± 0.37

6.85 ± 0.31

 

Hemoglobin content in peripheral blood

HCFC 122a

Concentrations

in 24 hours

in 48 hours

Control

12.3±0.5

12.1±0.6

2 mg/l

11.9 ± 0.6

12.2 ± 0.7

4 mg/l

12.1 ± 0.4

12.3 ± 0.3

6 mg/l

11.7 ± 0.3

12.2 ± 0.5

8 mg/l

12.4 ± 0.4

12.1 ± 0.3

10 mg/l

11.7 ± 0.6

11.9 ± 0.4

 

Sorbitol dehydrogenase amount in blood serum

HCFC 122a

Concentrations

in 24 hours

in 48 hours

Control

2.23±0.2

2.37±0.22

2 mg/l

2.16 ± 0.31

2.12 ± 0.29

4 mg/l

1.98 ± 0.27

2.45 ± 0.36

6 mg/l

2.36 ± 0.31

2.31 ± 0.4

8 mg/l

2.49 ± 0.37

1.89 ± 0.34

10 mg/l

3.68 ± 0.34

4.03 ± 0.36

 

 

Interpretation of results:
GHS criteria not met
Conclusions:
HCFC 122a is a low-toxic compound, the experimental value of LC50 = 72 mg/L is reported. The Lim ac (discriminating concentration under the test conditions) was established to be 4 mg/L.
Executive summary:

The objective of the reported study was to investigate the toxicity of HFCF 122a and HCFC 132 and to characterize their biological action in order to validate the approximate safe level of these compounds in the air of working area, ambient air, and water. In this study both a review of the available toxicological data on similar chemical compounds was made and toxicological tests on HFCF 122a and HCFC 132 were performed.

Evaluation of toxic properties by inhalation was conducted in 200 litre exposure chambers on white male rats with dynamic feeding of the substance.

The experiment assessed the concentrations of the two substances ranged from 5 to 100 mg/l.

The study showed that the LC50for HCFC 122a is 72 mg/l.

Clinical signs of poisoning in laboratory animals were symptoms of the nervous system damage: a short-term period of agitation followed by lethargy, drowsiness, muscle twitching, narcosis.

 

Moreover,the threshold value of acute effects Limacwas investigated. To this scope, and in order to establish the nature of the biological action, HCFC 122a was tested at the concentration of 2, 4, 6, 8, 10 mg/l and the following indicators were applied:

  • peripheral blood: erythrocytes, haemoglobin,
  • nervous system: summation-threshold value (STV), “hole exploratory behaviour”,
  • liver (SDH),
  • immunological reactivity (histamine),
  • respiration rate of animals

Indicators were recorded at 24 and 48 hours after a single exposure.

 

Four-hour exposure to HCFC 122a at a concentration of 4 mg/l caused a statistically significant reduction in orientation and exploratory activity in rats and increase in the summation-threshold value. Biological effect of 6 and 8 mg/l concentrations were further characterized by changes in respiratory rate and the concentration of 10 mg/l added to the described changes increase in sorbitol dehydrogenase, indicating liver damage. The detected changes fully recovered by the second day in groups of animals exposed to HCFC 122a at concentrations of 4 and 6 mg/l and persisted after exposure to the substance in large tested concentrations.

 

Basing on the results, the authors identified the substance as belonging at the of low-toxicity hazard class. Moreover, the concentrations of 6, 8 and 10 mg/l were considered as having effect upon single exposure, and the concentration of 4 mg/l as close to the Limac.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
72 000 mg/m³
Quality of whole database:
Although details on test method is not completely described in the quoted reference, the results are sufficient to aim a conclusion for the health hazard assessment of the substance.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The data source is authoritative. The results are sufficient to aim a conclusion for the health hazard assessment of the substance.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test was conducted in order to assess the skin absorption properties.
The study was conducted in two stages.
At the first stage the substance was applied in a single administration on the skin of the tails of white mice; contact time was 2 hours, after which the tails were washed with soap and water, and the animals were observed for 14 days.
Since the single exposure did not cause symptoms of intoxication and death of animals, a repeated applications of the substance for 12 days was included.
At this second stage the substance was applied to the section of rat skin sized 2 x 2 cm, and the application time was 4 hours. In order to prevent evaporation from the skin surface, the studied section of skin was sealed.
GLP compliance:
not specified
Test type:
other: subacute
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
4 hours/day x 12 days
Doses:
unchanged substance applied on 2x2 cmq of skin.
No. of animals per sex per dose:
no data
Control animals:
not specified
Dose descriptor:
LD50
Remarks on result:
other: not determined
Interpretation of results:
GHS criteria not met
Conclusions:
HCFC 122a does not posses potential toxicity following dermal exposure
Executive summary:

The objective of the reported study was to investigate the toxicity of HFCF 122a and HCFC 132 and to characterize their biological action in order to validate the approximate safe level of these compounds in the air of working area, ambient air, and water. In this study both a review of the available toxicological data on similar chemical compounds was made and toxicological tests on HFCF 122a and HCFC 132 were performed, including studies of skin absorption and acute toxicity by oral and inhalation routes.

Information on the acute toxicity of HCFC 122a by dermal exposure can be obtained from the study of skin absorption: under this test, in a first stage of the experiment, the toxicity of HCFC 122a was studied after application of the substances on the skin of the tails of the white mice; contact time was 2 hours after which the tails were washed with soap and water and the animals were observed for 14 days.

Since single exposure to the substances did not cause symptoms of intoxication and death of animals the experiments with repeated applications of HCFC 122a for 12 days were included. In this phase HCFC 122a was applied to the section of rat skin sized 2 x 2 cm, and the application time was 4 hours. In order to prevent evaporation of the substances from the skin surface, the studied section of skin was sealed.

The functional state of the experimental animals, used to determine if absorption occurred, was assessed based on some physiological parameters: orientation response and summation-threshold value (STV), the latter as index of adverse effect on the nervous system.

The method of summation of subthreshold pulses consists of recording of threshold stress causing the motor response. According to the authors it has a sufficiently high sensitivity for the detection of early changes in the condition of the nervous system.

These physiological parameters were chosen basing on the results of previous toxicological studies, which showed that the most evident signs of toxicity HCFC 122a and HCFC 132 are adverse effects on the nervous system.

Study showed that repeated application of HCFC 122a to the skin did not lead to changes in appearance and behaviour of animals and changes in functional parameters, indicating the absence of expressed skin-absorption properties. Basing on the results, it can be concluded that HCFC 122a does not posses potential toxicity following dermal exposure.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Although the test was not conducted according to test guidelines for acute dermal toxicity, the results are sufficient to aim a conclusion for the health hazard assessment of the substance.

Additional information

The acute toxicity following oral and inhalation exposure of HFCF 122a was investigated under a wide study conducted to characterize the biological action of some refrigerants and in order to validate the approximate safe level of these compound, including HCFC 122a, in the air of working area, ambient air, and water. The study included investigations of acute toxicity by oral route and inhalation, skin absorption, eye irritation/corrosion and skin sensitisation.

The results showed that HCFC 122a is a low-toxic compound since the experimental LD50 following oral exposure is reported to be 7800 mg/kg and the LC50 following inhalation is reported to be 72 mg/L.

 

Following both oral and inhalation exposure the clinical signs in animals predominantly consisted of symptoms of nervous system damage: a short-term period of agitation followed by lethargy, drowsiness, muscle twitching, narcosis.

Moreover, the threshold value of acute effects Limacfollowing inhalation was investigated. To this scope, HCFC 122a was tested at the concentration of 2, 4, 6, 8, 10 mg/l and a set of indicators of state were applied.

Four-hour exposure to HCFC 122a at a concentration of 4 mg/l caused a statistically significant reduction in orientation and exploratory activity in rats and increase in the summation-threshold value, the latter as index of adverse effect on the nervous system. The detected changes fully normalized by the second day of observation. Basing on the results, the concentration of 4 mg/l was identified as closed to the Limac.

 

Information on the acute toxicity of HCFC 122a by dermal exposure can be obtained from the study of skin absorption: under this test, in a first stage of the experiment, the toxicity of HCFC 122a was studied after application of the substance on the skin of the tails of the white mice; contact time was 2 hours after which the tails were washed with soap and water and the animals were observed for 14 days.

Since single exposure to the substances did not cause symptoms of intoxication and death of animals the experiments with repeated applications of HCFC 122a for 12 days were included. In this phase HCFC 122a was applied to the section of rat skin sized 2 x 2 cm, the application time was 4 hours and an occlusive coverage was applied. The study showed that repeated application of HCFC 122a to the skin did not lead to changes in appearance and behaviour of animals and changes in functional parameters, indicating the absence of expressed skin-absorption properties.

 

Basing on the results, it can be concluded that HCFC 122a does not posses potential toxicity following dermal exposure.

Justification for classification or non-classification

According to Regulation (EU) 1272/2008, HCFC 122a does not fulfill the classification criteria for the Acute Toxicity hazard classes.

However, following a single exposure by inhalation or oral administration, effects observed on the central nervous system included lethargy, drowsiness and justify a classification as Specific target organ toxicity – single exposure, Category 3 (STOT SE3), narcotic effects.