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Administrative data

Description of key information

- Acute oral: LD50/rat (males): 1605.3 mg/kg bw (Key study, Klimisch reliability 2, similar to OECD 401). Therefore, trifluoromethanesulphonic acid is considered as harmful if swallowed (category 4, H302).
- Acute dermal: inconclusive results due to severe ulceration at 2000 mg/kg bw (weight of evidence, Klimisch reliability 2, OECD 402 (screening test)). Therefore, a waiving based on the corrosivity of trifluoromethanesulphonic acid (category 1B, H314) was proposed.
- Acute inhalation: a waiving based on the corrosivity of trifluoromethanesulphonic acid (category 1B, H314) was proposed

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:
key study
Study period:
From 13 October 1987 to 4 November 1987.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study performed similarly to OECD guideline No. 401 but no data on GLP compliance. Only males are tested.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Kanpogyo Notification No. 39, Yakuhatsu Notification No. 229, and 59 Kikyoku Notification No., 85, dated 31 March 1984
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar Kyoto (WKY)
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Shizuoka Agricultural Cooperative Association for Laboratory Animals
- Age at study initiation: 5 weeks
- Weight at study initiation: 108.7 +/-3.4 g
- Fasting period before study: 17 hours prior to administration
- Housing: by groups of 5 in 310 mm W x 400 mm D x 200 mm H cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25°C
- Humidity (%): 45-65%
- Air changes (per hr): 15 times per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark /12 hrs light

IN-LIFE DATES: From: 13 October 1987 To 4 November 1987.
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: see Table 7.2.1/1
- Amount of vehicle (if gavage): 1 mL/100 g
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: no data

DOSAGE PREPARATION:
The test substance was diluted with distilled water to prepare the administration solutions at the prescribed concentrations as needed

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
As a preliminary test, 3 to 4 animals were administered 2000 and 500 mg/kg of the test substance. 3 of the 4 cases in the 2000 mg/kg group died, but no deaths were observed in the 500 mg/kg administration group. Based on these results, a dosage of 700 mg/kg was used as the standard and a common ratio of 1.3 established to set dosages within the range of 539 to 2000 mg/kg bw.
Doses:
0, 539, 700, 910, 1183, 1538 and 2000 mg/kg bw.
No. of animals per sex per dose:
10 males/dose

Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for death or overt signs of toxicity several times on the day of administration, and then at least once per day from the following day onward. Individual bodyweights were recorded prior to dosing on Day 0 and on days 3, 7, 10 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weigh and histopathology
Statistics:
LD50 value was calculated by the Probit method. The weights of the administration groups with at least 2 survival cases were assayed by determining the difference in average values between the control group and each administration group by means of a Student’s t-test or Welch’s test.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 1 605.3 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 402.1 - <= 1 941.8
Mortality:
- At 2000 mg/kg: 7/10 of dead animals
- At 1538 mg/kg: 6/10 of dead animals
-At 1183 mg/kg: 1/10 of dead animals
- At 910, 700 and 539 mg/kg: 0/10 of dead animals for each tested doses.
Clinical signs:
- At 2000 and 1538 mg/kg: decrease in spontaneous movement, crawling, sedation and emaciation were observed.
- At 1183 and 910 mg/kg: decrease in spontaneous movement and sedation were observed
- At 700 and 539 mg/kg: decrease in spontaneous movement was observed
These clinical signs were observed within hours after administration of the test substance and they were reversible.
Body weight:
Either weight loss or suppression of weight gain was observed 3 days post-administration in the groups administered 1183 mg/kg or more, and although there was a subsequent recovery trend, a difference was still noted in comparison with the control group when the observation period had ended.
Gross pathology:
- The necropsies of the fatal cases revealed gastric hemorrhaging, perforation, clouding and hyperemia of the small intestine, blackening and hypertrophy of the spleen, petechial hemorrhaging of the thymus, hemorrhaging of the bladder, and increase in pleural effusion.
- The necropsies of the survival cases revealed gastric erosion, scarring, thickening, adhesion of the stomach and liver, and thickening of the duodenum in the groups administered 1183 mg/kg or more.
Other findings:
- Histopathology:
Histopathological examinations revealed submucosal cellular infiltration in the stomach and small intestine. In strongly stimulated cases, adhesion of the stomach and liver reaching the muscle layer, serous membrane, and outside the serous membrane was observed. An extreme decrease in lymphocytes in the spleen was also observed.

Table 7.2.1/2: Autopsy findings in male rats treated with trifluoromethanesulfonic acid:

Dose (mg/kg)

0

539

700

910

1183

1538

2000

No. Of rats used

10

10

10

10

10

10

10

No. Of rats found dead

0

0

0

0

1

6

7

FINDINGS

Thymus:

-Petechia

0

0

0

0

1

0

0

Stomach:

-Perforation

-Hemorrhage

0

0

0

0

 

0

1

 

5

5

 

4

7

Small intestine:

-Cloudy white

-hyperemia

0

0

0

0

 

 

0

 

0

 

 

0

 

0

 

 

3

 

3

Spleen:

-Hypertrophy

-Black in color

0

0

0

0

 

0

0

 

0

0

 

2

3

Urinary bladder:

-Hemorrhage

-Pleural effusion increase

0

0

0

0

 

 

0

0

 

 

0

4

 

 

1

4

Advanced autolysis

0

0

0

0

0

1

0

Terminal killed

 

 

 

 

 

 

 

Stomach:

-Erosion

-Scar

-Thickening

0

0

0

0

 

0

0

7

 

3

1

4

 

0

1

3

Stomach and liver:

-Adhesion

0

0

0

0

0

1

1

Duodenum:

-Thickening

-No abnormalities detected

 

0

10

 

0

10

 

0

10

 

0

10

 

4

2

 

1

0

 

1

0

 

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the test conditions of this study, the acute median lethal dose (LD50) of trifluoromethanesulfonic acid was 1605.3 mg/kg body weight in the Wistar Kyoto (WKY) strain male rat. Based on this result, trifluoromethanesulphonic acid is classified as Harmful if swallowed in category 4, H302 according to the regulation (EC) No. 1272/2008 (CLP) and as Xn-R22 according to Annex VI of the Directive 67/548/EEC.
Executive summary:

In an acute oral toxicity study (KOBAYASHI, 1988) performed similarly to OECD guideline N° 401, groups of fasted Wistar Kyoto male rats (10/dose) were given a single oral dose of trifluoromethanesulphonic acid by gavage at the doses of 0 (vehicle only), 539, 700, 910, 1183, 1538 and 2000 mg/kg bw and observed for 14 days. Mortality and clinical signs were checked just after administration at 1, 2, 6 hours after dosing, and daily for 14 days. Body weight was recorded on days 0, 1, 2, 4, 7 and 14.

 

No males died at 539, 700 and 910 mg/kg bw whereas 1/10, 6/10 and 7/10 animals died when dosed at 1183, 1538 and 2000 mg/kg bw respectively.

Decrease in spontaneous movement, crawling, sedation and emaciation were observed but they were reversible.

All animals treated at 1183 mg/kg bw and more showed suppression of weight gain during the study.

Gastric erosion, scarring, thickening, adhesion of the stomach and liver and thickening of the duodenum were observed at necropsy. Histopathological examinations revealed submucosal cellular infiltration in the stomach and small intestine. In strongly stimulated cases, adhesion of the stomach and liver reaching the muscle layer, serous membrane, and outside the serous membrane was observed. An extreme decrease in lymphocytes in the spleen was also observed.

 

Under the conditions of this test, the Oral LD50 male rats = 1605.3 mg/kg (with 1402.1-1941.8 95% C.I.).

Based on these results, trifluoromethanesulphonic acid is considered as harmful if swallowed in category 4; H302 according to the regulation (EC) No. 1272/2008 (CLP) and as Xn, R22 according to the directive 67/548/EEC.

This acute oral study is classified as acceptable. It satisfies the guideline requirement for an acute oral study in the rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 605.3 mg/kg bw
Quality of whole database:
Two studies were available with good reliability (Kr. 2). The tests were performed in compliance with international guidance requirements with acceptable restrictions.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as corrosive to the skin
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as corrosive to the skin
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

1- Acute oral toxicity:

Two studies were available with reliability 2 according to Klimisch rating (Kr).

- A Kobayashi, 1988 study has been chosen as key study for this endpoint (Kr: 2). This study was conducted similarly to OECD guideline N° 401. Groups of fasted Wistar Kyoto male rats (10/dose) were given a single oral dose of trifluoromethanesulphonic acid by gavage at the doses of 0 (vehicle only), 539, 700, 910, 1183, 1538 and 2000 mg/kg bw and observed for 14 days. Mortality and clinical signs were checked just after administration, at 1, 2, 6 hours after dosing, and daily for 14 days. Body weight was recorded on days 0, 1, 2, 4, 7 and 14.

No males died at 539, 700 and 910 mg/kg bw whereas 1/6, 6/10 and 7/10 animals died when dosed at 1183, 1538 and 2000 mg/kg bw respectively.

Decrease in spontaneous movement, crawling, sedation and emaciation were observed but they were reversible.

All animals treated at 1183 mg/kg bw and more showed suppression of weight gain during the study.

Gastric erosion, scarring, thickening, adhesion of the stomach and liver and thickening of the duodenum were observed at necropsy. Histopathological examinations revealed submucosal cellular infiltration in the stomach and small intestine. In strongly stimulated cases, adhesion of the stomach and liver reaching the muscle layer, serous membrane, and outside the serous membrane was observed. An extreme decrease in lymphocytes in the spleen was also observed. Under the conditions of this test, the Oral LD50 male rats = 1605.3 mg/kg (with 1402.1-1941.8 95% C.I.).

- A study report (Longobardi, 2003) has been chosen as supporting study (Kr: 2).

In this acute oral toxicity study, 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 trifluoromethanesulphonic 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 such as 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, all these results show that trifluoromethanesulphonic acid is harmful by oral route

2- Acute Dermal toxicity:

One study was available with reliability 2 according to Klimisch rating.

A non-GLP study (Longobardi, 2003) was available. In this acute dermal toxicity study, performed similarly to the OECD guideline No. 402 (screening test), a single dose of undiluted trifluoromethanesulphonic 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 therefore conducted to 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 LD50 has been determined.

Based on the results of this study and in accordance with column 2 of REACH Annex VIII, the acute dermal study (required in section 8.5.3) does not need to be conducted as the substance is a strong acid (pH=0.11; acid reserve= 27,0 g NaOH/100g substance; see § 4.2) and classified as corrosive, therefore a waiving was proposed.

3- Acute Inhalation toxicity:

Trifluoromethanesulfonic acid is self-classified as corrosive category 1B, H314 according to the criteria of the Regulation (EC) 1272/2008 (CLP) and as corrosive to the skin (C, R34) according to the criteria of the Directive 67/548/EEC. Therefore, according to the column 2 of the Annex VIII of the Regulation (EC) NO. 1907/2006 (REACh) (section 8.5), an acute inhalation toxicity study does not need to be conducted if the substance is classified as corrosive to the skin.


Justification for selection of acute toxicity – oral endpoint
The key study was performed according to the OECD 401 guideline. However, the supporting study is a screening test.

Justification for selection of acute toxicity – inhalation endpoint
As Trifluoromethanesulphonic acid is classified as corrosive category 1B, H314; an acute inhalation toxicity study does not need to be conducted according to the column 2 of the Annex VIII of the Regulation (EC) NO. 1907/2006 (REACh).

Justification for selection of acute toxicity – dermal endpoint
In accordance with column 2 of REACh Annex VIII, the dermal acute study (required in section 8.5.3) does not need to be conducted as the substance is a strong acid (pH <2) and classified as corrosive (category 1B, H314).

Justification for classification or non-classification

1- Acute oral toxicity:

The LD50 (rat/males) is 1605.3 mg/kg bw and the LD50 (rat / (males + females)) is comprised between 500 and 2000 mg/kg bw. Based on these results, Trifluoromethanesulphonic acid is considered as harmful if swallowed in category 4, H302 according to the criteria of the Annex VI of the Regulation (EC) N° 1272/2008 (CLP) and as Xn-R22 according to the criteria of the Annex VI of the Directive 67/548/EEC.

2- Acute dermal toxicity:

Based on the available data (Longobardi, 2003), no conclusion can be established concerning the acute dermal toxicity of trifluoromethanesulphonic acid. However, as the substance is classified as corrosive, no further test has to be conducted. Therefore, no classification is possible due to lack of data.

3- Acute inhalation toxicity:

No data is available for this exposure route. However, as the substance is classified as corrosive, no further test has to be conducted. Therefore, no classification is possible due to lack of data.