Potassium trifluoroacetate

Endpoint summary

Description of key information

Based on the data currently available in the data set, both from the physico-chemical properties and toxicological data, absorption and systemic distribution of TFAK following oral administration is expected at least in the hydrophilic tissues.
Considering its vapor pressure, TFAK is not expected to be absorbed through the lungs by inhalation.
Considering the lack of effect in a dermal toxicological study, its physico-chemical properties and very low Kp, TFAK is not expected to be absorbed through the skin.
 
TFAK is not expected to be metabolized.
 
No indication of TFAK excretion was obtained but it is expected to be excreted in the urine.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

No data are available that describe the toxicokinetics of potassium trifluoroacetate. Therefore relevant substance properties and data from toxicity studies indicating systemic bioavailability were taken together to assess the general toxicokinetics of the substance.

Physico-chemical properties

Potassium trifluoroacetate has a water solubility of 697 g/L at 20°C, an octanol-water partition coefficient (log Kow) of <1 and negligible vapour pressure (< 10E-4 Pa at 25°C). The molecular weight of potassium trifluoroacetate is 152.1 g/mol. 

Absorption

Inhalation route

TFAK has a very low volatility as evidenced by its very low vapor pressure inferior at 10E-4 Pa at 25°C. It should therefore not be absorbed through inhalation.

Oral route

In an acute oral toxicity study Sprague-Dawley rats (3 males and 3 females per dose) received TFAK at doses of 500 and 2000 mg/kg in vehicle carboxymethylcellulose (CMC).

The clinical signs observed were: piloerection at 500 mg/kg (recovery within 2 days); piloerection and hunched posture at 2000 mg/kg with recovery within 6 days. There was no mortality and no abnormality was observed during necropsy.

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422) was performed with the reaction mass of TFSK and TFAK. The test item was administered orally by gavage once daily at dose levels of 100, 300 and 1000 mg/kg/body weight/day, for approximately 38 days for males and at maximum 57 days for females. No effects were observed on mortality, clinical observations, FOB, food consumption and body weight. The test item administration at 300 and 1000 mg/kg/day active ingredient induced centrilobular hepatocellular hypertrophy. This microscopic change correlated with increased liver weights. This change was not considered to be adverse in view of absence of associated degenerative microscopic findings or clinical pathology changes in liver enzyme activities. 

In the 90-day oral study, the structural analogue sodium trifluoroacetate was administered via the diet to male and female Wistar rats at concentrations of 160, 1600 and 16000 ppm (equating approx. to 11.2, 110, 1162 mg TFAK/kg bw/day in males and 13.4, 137 and 1359 mg TFAK/kg bw/day in females). The NOAEL for males and females was considered to be at 160 ppm based on an increase in liver weight, histopathological changes in the liver and changes in haematological parameters, clinical biochemistry and urinalysis.

The presence of clinical signs during the OECD 422 and OECD 408 study show that the test substance is absorbed in the gastrointestinal tract. 

 

Dermal Route

An acute dermal toxicity test was carried out on rats of both sexes (5 rats/sex) at 2000 mg/kg (active ingredients) with the reaction mass of TFSK and TFAK. The reaction mass was applied as supplied as a single dermal 24-hour exposure.

No mortality occurred during the study. Neither local dermal signs nor clinical signs were observed. Body weight was normal and necropsy displayed no evidence of any observations at a dose level of 2000 mg/kg bw (active ingredients).

 

A dermal irritation test was performed on one rabbit with TFAK where no irritation was observed.

 

A Local Lymph Node Assay was performed with TFAK. No sensitisation potential was detected in this test.

 

Despite a low molecular weight (152.11 g/mol), TFAK log Ko/w of -3.12, its high water solubility (697 g/L) and estimated permeability coefficient (Kp = 1.85x10^-6cm/hour on DERMWIN model http://www.epa.gov/oppt/exposure/pubs/episuite.htm) tend to support a limited capacity for absorption through the skin.

 

The absence of effects observed during dermal toxicological studies tend to show limited absorption through the skin but are not very relevant considering the low toxicological profile of TFAK. However, considering the physicochemical properties of TFAK it is not expected to penetrate the skin. TFAK does not have irritating properties that could increase dermal penetration.

 

Distribution

 

In a NMRI mouse micronucleus assay 5 to 15 males per dose were treated orally (gavage) with reaction mass of TFSK and TFAK at doses of 500, 1000 and 2000 mg/kg.

There was no mortality or signs of systemic toxicity during the study. No market effect of the test item treatment on the body weight of the mice was observed in the main test.

No biologically or statistically significant increases in the frequency of micronucleated polychromatic erythrocytes were seen.

 

During the rat acute oral toxicity studies some clinical signs were observed with TFAK at 2000 mg/kg (see oral absorption section).

 

During the rat repeated dose oral toxicity study with TFSK/TFAK reaction mass, some changes were observed in weight and/or histopathological examination of liver and spleen (see oral absorption section).

 

These results, together with the very high water solubility of TFAK, seem indicative of a systemic distribution at least in the hydrophilic tissues.

 

Metabolisation

 

TFAK is not expected to be metabolized.

 

Excretion

 

Owing to its low molecular weights and its high water solubility, TFAK is possibly excreted in the urine.

 

Conclusion

 

Based on the data currently available in the data set, both from the physico-chemical properties and toxicological data, absorption and systemic distribution of TFAK following oral administration is expected at least in the hydrophilic tissues.

Considering its vapor pressure, TFAK is not expected to be absorbed through the lungs by inhalation.

Considering the lack of effect in a dermal toxicological study, its physico-chemical properties and very low Kp, TFAK is not expected to be absorbed through the skin.

 

TFAK is not expected to be metabolized.

 

No indication of TFAK excretion was obtained but it is expected to be excreted in the urine.