Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
from 2000-02-28 to 2003-08-19
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Non-GLP study performed similarly to OECD guideline No. 404 (screening test) with some restrictions: no detail on the animal and environmental conditions.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From 2000-02-28 to 2003-08-19
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Non-GLP study performed similarly to OECD guideline No. 423 (screening test) with some restrictions: no detail on the animal and environmental conditions.
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Only 2 doses and three animals per doses are tested (screening test). No detailed information on animal and environment conditions.
GLP compliance:
no
Remarks:
Screening test.
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Nossan S.r.l, Italy
- Age at study initiation: no data
- Weight at study initiation: females: between 167 and 181 g; males: between 167 and 181 g.
- Fasting period before study: yes, food was removed overnight prior to dosing
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
other: 0.5% methocel (aqueous)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: two solutions were prepared: 50 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: no data

DOSAGE PREPARATION (if unusual): not applicable

CLASS METHOD (if applicable)
not applicable
Doses:
500 and 2000 mg/kg bw
No. of animals per sex per dose:
3 males dosed with 500 mg/kg bw
3 females dosed with 2000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical signs immediately upon dosing, approximately 1, 2 and 4 hours after dosing and then daily for a total of 14 days. Animals were weighed on allocation to the study, prior to the dosing (day 1) and on days 8 and 15.
- Necropsy of survivors performed: yes, animals were killed on day 15 by carbon dioxide narcosis.
- Other examinations performed: clinical signs, body weight, gross necrospsy examination.
Preliminary study:
No preliminary study was performed.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 500 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No males died at 500 mg/kg bw.
All females died when dosed at 2000 mg/kg bw. 2 animals died within 24 hours and the remaining animal died within 48 hrs.
Clinical signs:
males dosed with 500 mg/kg bw: piloerection was observed following dosing (recovery was observed within 3 days).
females dosed with 2000 mg/kg bw: piloerection, reduced activity/lethargy, hunched posture and pallor were observed following dosing.
Body weight:
All males dosed with 500 mg/kg bw showed an increased in body weight between the beginning and the end of the study. As all females died within 2 days, no information on body weight was available.
Gross pathology:
males dosed with 500 mg/kg bw: no significant abnormalities were observed.
females dosed with 2000 mg/kg bw: the abdominal cavity of 2 animals and the thoracic cavity of one animal contained a clear fluid material. Furthermore the jejunum of one animal contained a yellow mucoid material.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the test conditions of this study, trifluoromethanesulphonic acid is classified as acute oral toxicity in category 4, H302 (Harmful if swallowed) according to the criteria of the regulation (EC) No. 1272/2008 (CLP) and as harmful if swallowed (Xn, R22) according to the criteria of the Directive 67/548/EEC.
Executive summary:

In a non-GLP acute oral toxicity study (Longobardi, 2003) performed similarly to the OECD guideline No. 401 (screening test), groups of fasted Sprague-Dawley male and female rats were administered a single oral dose of trifluoromethanesulfonic acid (triflic acid) in 0.5 % methocel (aqueous) by gavage. The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

Three males were given an oral dose of 500 mg/kg bw and three females were dosed with 2000 mg/kg bw. No males died at 500 mg/kg bw whereas all females died within 48 hours when dosed at 2000 mg/kg bw. Furthermore males dosed with 500 mg/kg bw showed piloerection following dosing (recovery was observed within 3 days) while the clinical signs were more severe in females dosed at 2000 mg/kg bw: piloerection, reduced activity/lethargy, hunched posture and pallor. No significant abnormalities were observed at the necropsy for males dosed with 500 mg/kg bw whereas the abdominal cavity of 2 females and the thoracic cavity of one female dosed with 2000 mg/kg bw contained a clear fluid material. Furthermore the jejunum of one animal contained a yellow mucoid material.

 

The oral combined (male and female) LD50in rats was therefore comprised between 500 and 2000 mg/kg bw (500 < LD50≤ 2000 mg/kg bw).

 

In conclusion, under the test conditions, the test item trifluoromethanesulphonic acid is classified as acute oral toxicity in category 4, H302 (Harmful if swallowed) according to the criteria of the regulation (EC) No. 1272/2008 (CLP) and as harmful if swallowed (Xn, R22) according to the criteria of the Directive 67/548/EEC.

 

 

Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
from 2000-02-28 to 2003-08-19
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Non-GLP study performed similarly to OECD guideline No. 402 (screening test) with some restrictions: no detail on the animal and environmental conditions.
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Only 2 doses and three animals per doses are tested (screening test). No detail on the animal and environmental conditions.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Nossan S.r.l, Italy
- Age at study initiation: no data
- Weight at study initiation: females: between 204 and 242 g; males: between 267 and 268 g
- Fasting period before study: not required
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal surfaces of the trunk
- % coverage: 10%
- Type of wrap if used: the test item was spread over a gauze patch and covered by a tape dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated skin was vashed using warm water.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): not applicable, the test item is applied undiluted on the skin
- Constant volume or concentration used: no
- For solids, paste formed:not applicable, the test substance is a liquid

VEHICLE
not applicable, the test item is applied undiluted on the skin
Duration of exposure:
24 hours
Doses:
50 and 2000 mg/kg bw
No. of animals per sex per dose:
50 mg/kg bw: 3 females
2000 mg/kg bw: 3 males
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs: immediately upon dosing, approximately 1, 2 and 4 hours after dosing and daily thereafter for a total of 14 days. Weighing: on allocatio of the study, prior to dosing (day 1) and on days 8 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 50 mg/kg bw
Based on:
test mat.
Remarks on result:
other: the test results are unconclusive because of severe local effects on the skin at 2000 mg/kg bw
Mortality:
No mortalities were observed at 50 mg/kg bw. At 2000 mg/kg bw, all animals were humanly killed before the end of the test.
Clinical signs:
At 50 mg/kg bw, the test item is tolerated, both at the treated site and systematically, whereas at 2000 mg/kg bw, extensive local effects on the skin following the dosing were observed. Indeed ulceration of the treated skin was observed following exposure. This local effect was sufficiently severe to be life-threatening and therefore to conduct to the humanely kill of all animals dosed at 2000 mg/kg bw.
Body weight:
At 50 mg/kg bw, the body weight gain of all animals is positive (between 10 and 15 g gained between day 1 and day 15).
At 2000 mg/kg bw, the body weight was only measured prior to dosing as the animals were then rapidly killed because of severe local effects.
Gross pathology:
At 50 mg/kg bw, no significant abnormalities were observed.
At 2000 mg/kg bw, dark staining around treated site was observed with an extensive open wound with oedema of the sub-cutis.
Interpretation of results:
study cannot be used for classification
Remarks:
Because of severe local effects, the study was interrupted
Conclusions:
Under the test conditions, no conclusions can be established as severe local effects were observed at 2000 mg/kg bw. The test was therefore interrupted before the end of the recommended observation period and no clear LD50 has been determined.
Executive summary:

In a non-GLP acute dermal toxicity study (Longobardi, 2003) performed similarly to the OECD guideline No. 402 (screening test), a single dose of undiluted trifluoromethanesulfonic acid (triflic acid) was applied on the shaved skin of Sprague-Dawley male and female rats. The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

Three females received a dermal dose of 50 mg/kg bw and three males were dosed with 2000 mg/kg bw.No females died at 50 mg/kg bw whereas all males suffered from ulceration of the skin following the application of the test item at 2000 mg/kg bw. At 50 mg/kg bw, the test item is tolerated, both at the treated site and systematically, whereas at 2000 mg/kg bw, extensive local effects on the skin following the dosing were observed. Dark staining around treated site was observed with an extensive open wound with oedema of the sub-cutis. Therefore the skin ulceration was sufficiently severe to be life-threatening and conducted to the humanely kill all animals dosed at 2000 mg/kg bw.

 

Therefore under the test conditions, no conclusion can be established as severe local effects were observed at 2000 mg/kg bw. The test was interrupted before the end of the recommended observation period and no clear LD50has been determined.

 

Reason / purpose:
reference to same study
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
from 2000-02-28 to 2003-08-19
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Non-GLP study performed similarly to OECD guideline No. 406 (screening test), no detail on the animal and environmental conditions.
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
: screening tets, no detail on the animal and environmental conditions.
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
screening test
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An in vivo LLNA method in not necessary since data from an in vivo guinea pig maximisation test are available. In addition, the substance is classified corrosive.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Nossan, S.r.l, Italy
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: not required
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Route:
intradermal and epicutaneous
Vehicle:
water
Remarks:
sterile
Concentration / amount:
Induction: intradermal injection: 0.1%: topical application: 10%
Challenge: 1%
Route:
other: epicutaneous
Vehicle:
water
Remarks:
sterile
Concentration / amount:
Induction: intradermal injection: 0.1%: topical application: 10%
Challenge: 1%
No. of animals per dose:
5 animals for the test group
3 animals for the control group
Details on study design:
RANGE FINDING TESTS: One animal was exposed by intradermal injection to the test item at different concentrations (from 0.1 to 10%) and the signs of skin irritancy were observed 6 days after the exposure. Two other animals were exposed by topical application to the test item at different concentrations (from 1 to 30%) and the signs of skin irritancy were analysed 7 days following the exposure. See results of the range findings study in Tables 7.4.1/1 and 7.4.1/2.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: no data
- Test groups: For the intradermal and topical exposure: 3 sites of application on each animal: Freund's complete adjuvant (FCA), Test item in water, Test item in FCA. For the topical application, the animals were pre-treated with sodium lauryl sulphate to promote an irritant reaction and then exposed as explained just before.
- Control group: For the intradermal and topical exposure: 3 sites of application on each animal: Freund's complete adjuvant (FCA), water only , water + FCA. For the topical application, the animals were pre-treated with sodium lauryl sulphate to promote an irritant reaction and then exposed as explained just before.
- Site: no data
- Frequency of applications: the topical application was performed one week following the intradermal injection. Single exposure in each case.
- Duration: no data
- Concentrations: 0.1% for the intradermal injection, 10% for the topical application

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Two weeks after the second induction stage, ie. 21 days after the first induction stage
- Exposure period: no data
- Test groups: topical application of the test item in water
- Control group: topical application of water only
- Site: no data
- Concentrations: 1%
- Evaluation (hr after challenge): 24 and 48hrs
Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no data
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no data
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
-
No. with + reactions:
0
Total no. in group:
3
Clinical observations:
no data
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
-
No. with + reactions:
0
Total no. in group:
3
Clinical observations:
no data
Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test item trifluoromethanesulfonic acid (triflic acid) is not classified as Skin sensitiser according to the criteria of the Regulation (EC) 1272/2008 (CLP) and of the annex VI of the Directive 67/548/EEC.
Executive summary:

In a non-GLP skin sensitisation study performed similarly to the OECD No. 406 (screening test), Dunkin-Hartley guinea pigs were exposed to trifluoromethanesulfonic acid (triflic acid) diluted in sterile water (vehicle). In a preliminary study the skin irritation potential of the test item was assessed in one animal after an intradermal injection with Freund’s complete adjuvant and on two animals following a topical application. Six days after an intradermal injection, the test item from 1% to 10% induced necrosis of the skin. At 0.1 and 0.5% of test item erythema was observed. The concentration of 0.1% was chosen for the first induction stage as only a slight erythema reaction was observed (score 1). Seven days after a topical application of sodium lauryl sulphate (to promote the skin irritation) followed by a topical application of the test item diluted in water, no signs of irritation was observed at 1and 5%. At 10% a slight irritation was observed, therefore this concentration was chosen for the second induction stage.

In the main study performed on 5 animals for the test group and 3 animals for the control group, three test sites were tested in each animal. In the first induction stage intradermal injections of Freund’s complete adjuvant (FCA), or of the test item (0.1%) with FCA, or of the test item (0.1%) in vehicle were performed on each animal. One week later, the animals were pre-treated with sodium lauryl sulphate (to promote a skin irritation) and then topically exposed to the test item at 10% in sterile water. Two weeks following this second induction stage, animals were challenged by a topical application of the test item (1%) in water. 24 and 48 hrs after the challenge, no skin reaction was observed in any animal of the test group or of the control group. The body weight gain was comparable in the test animals and the control animals.

In conclusion, under the test conditions, the test item trifluoromethanesulfonic acid (triflic acid) is not classified as skin sensitiser according to the criteria of the Regulation (EC) 1272/2008 (CLP) and of the annex VI of the Directive 67/548/EEC.

This study is considered as acceptable as it satisfies the criteria of the OECD guideline No.406 (screening test).

Reason / purpose:
reference to same study
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
from 2000-02-28 to 2003-08-19
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Non-GLP study performed similary to the OECD guideline No. 471 with some restrictions. Indeed a screening test was performed with only two bacterial strains used, only one experiment, 2 replicates per concentration.
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
: screening test: a single experiment was performed (with duplicate); only 2 strains were tested (TA98 and TA100)
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay
Target gene:
Each strains derived from S. thyphimurium LT2 contains one mutation in the histine operon, resulting in a requirement for histidine.
Species / strain / cell type:
S. typhimurium TA 98
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 100
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 mix
Test concentrations with justification for top dose:
61.7; 185; 556; 1670 and 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data
Untreated negative controls:
yes
Remarks:
untreated
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-nitrofluorene (2NF) for TA 98 in absence of S9; sodium azide (NaN3) for TA 100 in absence of S9; 2-Aminoanthracene for TA 98 and TA 100 with S9
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation): 2 mL overlay agar (held at 45°C), 0.1 mL test or control substance solution, 0.5 mL S9 mix, 0.1 mL bacterial suspension

DURATION
- Preincubation period: not applicable
- Exposure duration: 72 hours at 37°C
- Expression time (cells in growth medium): not applicable
- Selection time (if incubation with a selection agent): not applicable
- Fixation time (start of exposure up to fixation or harvest of cells): not applicable

SELECTION AGENT (mutation assays): not applicable
SPINDLE INHIBITOR (cytogenetic assays): not applicable
STAIN (for cytogenetic assays): not applicable

NUMBER OF REPLICATIONS: A single experiment was performed with 2 replicate per condition.

NUMBER OF CELLS EVALUATED: all revertant colonies in the plate were counted

DETERMINATION OF CYTOTOXICITY
- Method: thining of the background lawn
Evaluation criteria:
A reproducible 2-fold increase in the number of revertants compared with the vehicle controls was considered as a positive result.
Species / strain:
S. typhimurium, other: TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
see details in tables 7.6.1/1 and 7.6.1/2
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Thinning of the background lawn at 5000 µg/plate in both strains, both in absence and presence of S9 mix
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
no data

RANGE-FINDING/SCREENING STUDIES: not applicable as no range-finding study was performed

COMPARISON WITH HISTORICAL CONTROL DATA: no data

ADDITIONAL INFORMATION ON CYTOTOXICITY: no additional information

Table 7.6.1/1: Number of revertants per plate (mean of duplicates) in the absence of metabolic activation (direct plate incorporation method)

Triflic acid Concentration
(µg/plate)

TA 98

TA 100

Mean

Standard deviation

Mean

Standard deviation

Untreated

34

1.0

132

3.0

0*

31

1.0

126

1.0

61.7

31

1.5

125

1.0

185

34

1.0

133

1.5

556

32

0.5

137

2.5

1670

30

2.5

126

5.5

5000

32

3.0

115

1.5

Positive control

DMSO (100 µg/plate) for TA98, Untreated for TA100

31

1.0

132

3.0

Positive control**

201

2.5

935

9.0

*Solvent control = DMSO

**Mutagens positive controls:

- 2NF (2 µg/plate) in TA 98 strain

- NaN3(1 µg/plate) in TA100 strain

 

Table 7.6.1/2: Number of revertants per plate (mean of duplicates) in the presence of metabolic activation (direct plate incorporation method)

Triflic acid Concentration
(µg/plate)

TA 98

TA 100

Mean

Standard deviation

Mean

Standard deviation

Untreated

46

1.5

145

0.5

0*

45

3.0

147

7.5

61.7

41

1.0

133

3.0

185

41

3.0

140

1.5

556

45

3.0

137

2.0

1670

42

3.0

133

4.5

5000

40

3.5

128

4.5

Positive control

DMSO (100 µg/plate)

45

3.0

147

7.5

Positive control**

745

28.0

1080

14.5

*Solvent control = DMSO

**Mutagens positive controls:

- 2-aminoanthracene: 1 µg/plate

Conclusions:
Interpretation of results:
negative with and without metabolic activation (TA 98 and TA 100)

Under the test conditions, the test item trifluoromethanesulfonic acid (triflic acid) did not show mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium TA 98 and TA 100.
Executive summary:

In a non-GLP reverse gene mutation assay in bacteria (Cinelli, 2003), performed similarly to the OECD guideline No.471(screening test), strains TA100 and TA98 of Salmonella typhimurium were exposed to trifluoromethanesulfonic acid (triflic acid) diluted in dimethylsulfoxide (DMSO) at concentrations of 61.7, 185, 556, 1670 and 5000 µg/plate in the presence and absence of mammalian metabolic activation.The method of direct incorporation was tested. No pre-test was performed and only one test was realized with two plates per concentration.

Trifluoromethanesulfonic acid was tested up to limit concentration (5000 µg/plate) and cytotoxicity was observed at this highest concentration (thinning of the background lawn) in any strains, with and without metabolic activation. However, the test item did not induce a 2-fold increase in the number of revertant colonies of either strain tested, with or without metabolic activation, at any concentration.

The positive controls (2-nitrofluorene; sodium azide; 2-aminoanthracene) induced the appropriate responses in the corresponding strains.

In conclusion, under the test conditions, the test itemTrifluoromethanesulfonic acid did not show mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium TA98 and TA100 as there was no evidence of induced mutant colonies over background.

 

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
screening test: no detail on the animal and environmental conditions
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
gas under pressure: refrigerated liquefied gas
Details on test material:
- Name of test material (as cited in study report): trifluoromethanesulfonic acid (triflic acid)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Italia S.p.A.
- Age at study initiation: no data
- Weight at study initiation: 2.7 kg
- Fasting period before study: no
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): not applicable, the test item is applied undiluted

VEHICLE
not applicable, the test item is applied undiluted
Duration of treatment / exposure:
3 min, 1 hour or 4 hours. Three sites in the same animal were treated with the test item.
Observation period:
1, 24, 48 and 72 hours and 7 days after the end of exposure.
Number of animals:
one animal
Details on study design:
TEST SITE
- Area of exposure: dorsal surface of the trunk
- % coverage: 6.25 cm² (2.5 x 2.5 cm)
- Type of wrap if used: the test item was spread over a gauze square but no data on the dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data but probably yes.
- Time after start of exposure: no data but probably 3 min, 1 hour and 4 hours after the application of the test item.

SCORING SYSTEM: no data

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
Mean individual score after 3 min exposure
Time point:
other: Overall 24, 48 and 72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
Mean individual score after 3 min exposure
Time point:
other: Overall 24, 48 and 72 h
Score:
1
Reversibility:
not reversible
Remarks:
within 7 days
Remarks on result:
other: necrosis on day 7
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
Mean individual score after 1 hour exposure
Time point:
other: Overall 24, 48 and 72 h
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
Mean individual score after 1 hour exposure
Time point:
other: Overall 24, 48 and 72 h
Score:
1
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: start of necrosis at 72 hrs
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
Mean individual score after 4 hours exposure
Time point:
other: Overall 24, 48 and 72 h
Score:
1.3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
Mean individual score after 4 hours exposure
Time point:
other: Overall 24, 48 and 72 h
Score:
1.3
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: start of necrosis at 72 hrs
Irritant / corrosive response data:
Brown coloration, hardening were observed within 1 hour (after 1 or 4 hours exposure) or 24 hours (after 3 min exposure) after the end of the exposure period. Erythema around the site of application was observed 24 hours after the end of exposure in the cases of 1 and 4 hours exposure.
Necrosis was observed 7 days after the exposure period and for all exposure time (3 min, 1 hr or 4 hrs). See details in Table 7.3.1/1.

Any other information on results incl. tables

Table 7.3.1/1: Irritant/corrosive response data at each observation time up to removal of animal from the test (3 min, 1 or 4 hrs exposure)

 

3 min exposure

1 hour exposure

4 hours exposure

Score at time point / Reversibility

Erythema

Edema

Erythema

Edema

Erythema

Edema

Max. score: no data

Max. score: no data

Max. score: no data

Max. score: no data

Max. score: no data

Max. score: no data

60 min

0

0

-

0

-

2

24 h

0

1

1

1

2

2

48 h

0

1

1

1

1

1

72 h

0

1

1

1

1

1

Average 24h, 48h, 72h

0.0

1.0

1.0

1.0

1.3

1.3

Reversibility*)

-

n

?

n

?

n

 *) Reversibility: c. = completely reversible;n.c.= not completely reversible; n. = not reversible; ?: no data

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Under the test conditions, the test item trifluoromethanesulfonic acid (triflic acid) is classified as Skin Corr./Irr. 1B (H314; causes severe skin burns and eye damage) when applied topically to rabbits according to the criteria of the Regulation (EC) 1272/2008 (CLP) and as skin corrosive (C, R34; Causes burns) according to the criteria of the annex VI of the Directive 67/548/EEC.
Executive summary:

In a non-GLP dermal irritation study (Longobardi, 2003) performed similarly to the OECD No. 404 (screening test), one New Zeland White rabbit was dermally exposed to 0.5 mL of undiluted trifluoromethanesulfonic acid (triflic acid) to the dorsal surface of the trunk (skin was shaved before application). Three test sites were covered with a semi-occlusive dressing and tested in the same animal corresponding to 3 different time of exposure: 3 min, 1hr or 4hrs. After the removal of the gauze patch, animals were then observed for 7 days. Skin irritation was assessed and scored at 1, 24, 48, 72 hrs and 7 days after the end of the exposure.  

The mean individual scores calculated within 3 scoring times (24, 48 and 72 hrs) were 0.0 for erythema and 1.0 for edema after a 3 min exposure period, 1.0 for erythema and 1.0 for edema after a 1 hr exposure period and 1.3 for erythema and 1.3 for edema after a 4 hr exposure period. Indeed brown coloration, hardening were observed within 1 hour (after 1 or 4 hours exposure) or 24 hours (after 3 min exposure) after the end of the exposure period. Erythema around the site of application was observed 24 hours after the end of exposure in the cases of 1 and 4 hours exposure. Necrosis was observed 7 days after the exposure period and for all exposure time (3 min, 1 hr or 4 hrs) and started to occur within 72 hrs observation after a 1 or 4 hr exposure period.

In conclusion, under the test conditions, the test item trifluoromethanesulfonic acid (triflic acid) is classified as Skin Corr./Irr. 1B (H314; causes severe skin burns and eye damage) when applied topically to rabbits according to the criteria of the Regulation (EC) 1272/2008 (CLP) and as skin corrosive (C, R34; Causes burns) according to the criteria of the annex VI of the Directive 67/548/EEC.