Registration Dossier

Administrative data

Description of key information

Skin irritation: 
Not irritating; OECD guideline 404; GLP compliant; very slight skin reactions, reversible within 72 h
Eye irritation:
Not irritating; OECD Guideline 405; GLP compliant; only minimal irritation, reversible within 48 h

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1985-05-08 to 1985-05-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.44 -3.01 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): standard laboratory diet, ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5±1.5°C
- Humidity (%):50-55%
- Air changes (per hr): approx. 10/h
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5x2.5 cm
- Type of wrap if used: patches were held in place with Sleek adhesive strapping; elasticated corset

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, any residual test material was removed by gently swabbing cotton wool soaked in ether
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize (OECD 404)
Irritation parameter:
erythema score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No irritating effects were noted in any animal during the observation period.

Rabbit number

reaction

1/24/48/72h

1

erythema

0/0/0/0

edema

0/0/0/0

2

erythema

0/0/0/0

edema

0/0/0/0

3

erythema

0/0/0/0

edema

0/0/0/0

Interpretation of results:
GHS criteria not met
Conclusions:
TFMEA was not irritating to rabbit skin in this study.
Executive summary:

In a primary dermal irritation study according to OECD guideline 404, 3 young adult New Zealand White rabbits were dermally exposed to 0.5 mL of undiluted TFMEA (purity not given in the study report, but according to sponsor >90%) for 4 h hours to 6.25 cm² body surface area. Animals then were observed for 3 days.  Irritation was scored by the method of Draize.

No irritating effects were noted in any animal during the observation period.

In this study, TFMEA is not a dermal irritant.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1991-12-31 to 1992-01-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 12 – 16 weeks
- Weight at study initiation: 2.39 – 2.53 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: min 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 21°C
- Humidity (%): 49 – 54%
- Air changes (per hr): app. 15/h
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3 (2 females, 1 male)
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: patches secured with surgical adhesive tape + wrapped in an elasticated corset

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 h

SCORING SYSTEM: as stipulated in OECD guideline 404 (Draize scale)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Very slight erythema (grade 1) was observed at all treated skin sites 1 and 24 h after patch removal and in two animals 48 h after patch removal.
Very slight edema (grade 1) was observed in one animal at the 24 h observation.
All effects were reversible within 72 h.

Scores

Animal 1

Animal 2

Animal 3

1/24/48/72 h

1/24/48/72 h

1/24/48/72 h

Erythema/eschar

1/1/1/0

1/1/0/0

1/1/1/0

Edema

0/0/0/0

0/0/0/0

0/1/0/0

Interpretation of results:
GHS criteria not met
Conclusions:
TFMEA was not irritating to the skin in this study.
Executive summary:

In a primary dermal irritation study according to OECD guideline 404, 1981, 3 12 to 16 weeks old New Zealand white rabbits were dermally exposed to 0.5 mL of TFMEA (purity not given in the study report, but according to sponsor >90%) for 4 h to 2.5 cm x 2.5 cm body surface area. Animals then were observed for 3 days. Irritation was scored by the Draize method (OECD guideline 404).

Very slight erythema (grade 1) was observed at all treated skin sites 1 and 24 h after patch removal and in two animals 48 h after patch removal. Very slight edema (grade 1) was observed in one animal at the 24 h observation. All effects were reversible within 72 h.

 

TFMEA was not irritating to the skin in this study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1985-05-13 to 1985-05-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.48 – 2.69 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): standard laboratory diet, ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5±1.5°C
- Humidity (%):50-55%
- Air changes (per hr): approx. 10/h
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated contralateral eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
eyes were not rinsed after application
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: standard ophthalmoscope (Keeler)
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Conjunctival redness (grade 1, some blood vessels hyperaemic (injected)) was observed in 3/3 animals after 1 h and in 2/3 animals after 24 h. Grade 1 chemosis was observed in 1/3 animals after 1 h, which had recovered at the 24 h time point. No irritation was noted at the 48 and 72 h observations.

Rabbit number

reaction

Scores

1/24/48/72 h

1

Cornea, opacity

0/0/0/0

Iris

0/0/0/0

Conjunctivae, redness

1/1/0/0

Conjunctivae, chemosis

0/0/0/0

Conjunctivae, discharge

0/0/0/0

2

Cornea, opacity

0/0/0/0

Iris

0/0/0/0

Conjunctivae, redness

1/1/0/0

Conjunctivae, chemosis

1/0/0/0

Conjunctivae, discharge

0/0/0/0

3

Cornea, opacity

0/0/0/0

Iris

0/0/0/0

Conjunctivae, redness

1/0/0/0

Conjunctivae, chemosis

0/0/0/0

Conjunctivae, discharge

0/0/0/0

Interpretation of results:
GHS criteria not met
Conclusions:
In this study TFMEA was not irritating to the eye.
Executive summary:

In a primary eye irritation study according to OECD guideline 405, 0.1 mL of undiluted TFMEA (not given in the study report, but according to sponsor >90%) was instilled into the conjunctival sac of the right eye of 3 young adult New Zealand white rabbits. The eyes were not rinsed after application. Animals then were observed for 3 days.  Irritation was scored by the method of Draize.

Only minimal irritation was observed:Conjunctival redness (grade 1, some blood vessels hyperaemic (injected)) was observed in 3/3 animals after 1 h and in 2/3 animals after 24 h. Grade 1 chemosis was observed in 1/3 animals after 1 h, which had recovered at the 24 h time point. No irritation was noted at the 48 and 72 h observations.

In this study, TFMEA is not an eye irritant. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Reliable (RL=1-2), relevant and adequate data are availablefor the skin and eye irritation potential of TFMEA.

 

Skin irritation

In a primary dermal irritation study according to OECD guideline 404, 1981, 3 12 to 16 weeks old New Zealand white rabbits were dermally exposed to 0.5 mL of TFMEA (purity not given in the study report, but according to sponsor >90%) for 4 h to 2.5 cm x 2.5 cm body surface area. Animals then were observed for 3 days. Irritation was scored by the Draize method (OECD guideline 404).

Very slight erythema (grade 1) was observed at all treated skin sites 1 and 24 h after patch removal and in two animals 48 h after patch removal. Very slight edema (grade 1) was observed in one animal at the 24 h observation. All effects were reversible within 72 h.TFMEA was not irritating to the skin in this study.

 

In a primary dermal irritation study according to OECD guideline 404, 3 young adult New Zealand White rabbits were dermally exposed to 0.5 mL of undiluted TFMEA (purity not given in the study report, but according to sponsor >90%) for 4 h hours to 6.25 cm² body surface area. Animals then were observed for 3 days.  Irritation was scored by the method of Draize. No irritating effects were noted in any animal during the observation period. In this study, TFMEA is not a dermal irritant.

 

Eye irritation

Before conducting an in vivo eye irritation study, the potential to cause corrosive effects to the eye was assessed in an in vitro assay:

TFMEA (99.92% a.i.) was tested in the hen's egg chorioallantoic membrane test (HET-CAM), an accepted alternative method to the Draize test, to evaluate the acute irritation potential. The potential to cause irritation upon first contact with eyes or mucous membranes was assessed by application of the test substance onto the chorioallantoic membrane (CAM) of 3 fertilised and incubated eggs (strain Leghorn).

0.3 mL of pure or diluted test substance was applied drop by drop onto the membrane. The time of appearance of hyperaemia, haemorrhage, coagulation and lysis was noted in seconds. Observation lasted for 5 minutes. Treatment with the test substance resulted in hyperaemia in all 3 eggs within 14 - 29 s after treatment with the undiluted test substance (mean index 6.4 of 21 possible scores; moderately irritating) and in 2 eggs within 121 or 184 s after treatment with the test substance at a concentration of 10% (mean index 2.4 of 21 possible scores; slightly irritating). No other effect was detected after treatment. Thus, the test substance was graded as moderately irritating according to the evaluation scheme.

As the substance was not classified as corrosive, an in vivo test was required for further assessment:

In a primary eye irritation study according to OECD guideline 405, 0.1 mL of undiluted TFMEA (not given in the study report, but according to sponsor >90%) was instilled into the conjunctival sac of the right eye of 3 young adult New Zealand white rabbits. The eyes were not rinsed after application. Animals then were observed for 3 days.  Irritation was scored by the method of Draize.

Only minimal irritation was observed: Conjunctival redness (grade 1, some blood vessels hyperaemic (injected)) was observed in 3/3 animals after 1 h and in 2/3 animals after 24 h. Grade 1 chemosis was observed in 1/3 animals after 1 h, which had recovered at the 24 h time point. No irritation was noted at the 48 and 72 h observations. In this study, TFMEA is not an eye irritant. 

 

Respiratory irritation

No data on the respiratory irritation of TFMEA are available.

 

There are no data gaps for the endpoint irritation/corrosion. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.


Justification for classification or non-classification

Based on the available data, TFMEA does not need to be classified for skin irritation according to CLP, EU GHS (Regulation (EC) No 1272/2008) or Directive 67/548 EEC.