Registration Dossier

Administrative data

Description of key information

No acute toxicity studies with fatty acids, C9 -13 neo, potassium salts are available, thus the acute toxicity will be addressed with existing data on the individual moieties potassium and neodecanoate. Signs of acute oral or acute dermal toxicity are not expected for fatty acids, C9 -13 neo, potassium salts, since the two moieties potassium and neodecanoic acid have not shown signs of acute oral or acute dermal toxicity in experimental testing (both LD50 > 2000mg/kg).

 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Potassium

 

Potassium is an essential mineral in the human diet. It is the predominant osmotically active element inside cells and contributes to establishing a membrane potential in nerve fibres and muscle cells. Potassium is present in natural foods and the average potassium intake range between 2500- 4000 mg/day in adults. No tolerable upper intake level (UL) has been set for potassium by EFSA due to insufficient data (EFSA, 2005). “There are no reports of adverse effects associated with potassium naturally-occurring in food in healthy subjects. It also stated that long-term intakes of about 3000 mg potassium/day as potassium chloride supplements, in addition to intake from food, have been shown not to have adverse effects in healthy adults (Cappuccio et al., 2016).

“Short-term studies (2-3 weeks) on healthy adults have shown that serum potassium levels were within normal ranges at intakes up to around 15 g potassium per day, provided that fluid intake is sufficient and that intake is evenly distributed over the day (FNB, 2004; Rabelink et al., 1990). In a metabolic ward study by Rabelink et al. (1990) six healthy young subjects (3 males and 3 females) were given a KCl solution to the meals (in total 3.9 g K per meal), which were provided every sixth hour during a 20-day period, i.e. one meal was given during the night, as well 200 mL water was given hourly. The total intake of potassium was 15.6 g/day. Plasma potassium levels rose initially and the mean level after 48 hours was 4.77 mmol/L. About 95 % of the ingested potassium was excreted in the urine. The plasma levels then decreased and remained stable throughout the study period. A similar, but more pronounced pattern was seen for aldosterone and plasma renin activity. There was an indication of some initial volume loss, e.g. fall in body weight, which normalized during the study period. This study indicates that intakes up to about 15 g/day, distributed over the day and with adequate fluid intake, may be tolerated in healthy subjects without exceeding the normal range of serum potassium, at least under metabolic ward conditions” (EFSA, 2005).

“Acute high doses of potassium might, however, exceed the capacity of the kidney to eliminate potassium and thereby lead to elevated serum potassium levels and disturbed clearance of for example urea. In a study by Keith et al. (1941) seven normal subjects received single doses of 9.5-17.5g potassium chloride or bicarbonate (4.9-6.8g K) in solutions after having a standardized breakfast. In two of the subjects, who received a single dose of 12.5 or 17.5g potassium chloride or bicarbonate, respectively (6.5-6.8g K), symptoms as increased T-wave ECG and paresthesia of hands and feet in parallel with marked/or severe hyperkalaemia (8 mmol/L) were observed within 2-3 hours. However, symptoms did not appear in other subjects receiving the same amount of potassium. The data indicate that acute intakes of 80- 100 mg/kg body weight (equivalent to 4.8-6g for a 60kg person) could cause acute adverse effects in some apparently normal subjects” (EFSA, 2005). “Case reports of adverse effects associated with high doses of potassium containing supplements (KCl) and salt substitutes have described chest tightness, nausea and vomiting, diarrhoea, hyperkalaemia, shortness of breath and heart failure. The reported doses causing acute effects were 1-94g/day in adults and 1.5-7g/day in infants. Fatal cases of acute or chronic potassium intake have been reported. For example, a fatality resulted from hyperkalaemia and resultant asystole after ingestion of 21g of salt substitute representing an oral bolus of 11g potassium (Restuccio, 1992). A 2 month-old boy died after being given three doses of 1.5g potassium chloride in two days (2.3g potassium in total), with breast milk over one and a half days (Wetli and Davis, 1978)” (EFSA, 2005).

 

Acute dermal toxicity

 

In the absence of measured data on dermal absorption, current guidance suggests the assignment of either 10 % or 100 % default dermal absorption rates. In contrast, the currently available scientific evidence on dermal absorption of metals yields substantially lower figures, which can be summarised briefly as follows:

Measured dermal absorption values for metals or metal compounds in studies corresponding to the most recent OECD test guidelines are typically 1 % or even less. Therefore, the use of a 10 % default absorption factor is not scientifically supported for metals. This is corroborated by conclusions from previous EU risk assessments (Ni, Cd, Zn) and current metal risk assessments under REACH, which have derived dermal absorption rates of 2 % or far less (but with considerable methodical deviations from existing OECD methods) from liquid media.

However, considering that under industrial circumstances many applications involve handling of dry powders, substances and materials, and since dissolution is a key prerequisite for any percutaneous absorption, a factor 10 lower default absorption factor may be assigned to such “dry” scenarios where handling of the product does not entail use of aqueous or other liquid media. This approach was taken in the in the EU RA on zinc. A reasoning for this is described in detail elsewhere (Cherrie and Robertson, 1995), based on the argument that dermal uptake is dependent on the concentration of the material on the skin surface rather than it’s mass.

The following default dermal absorption factors for metal cations are therefore proposed (reflective of full-shift exposure, i.e. 8 hours):

From exposure to liquid/wet media: 1.0 %

From dry (dust) exposure: 0.1 %

This approach is consistent with the methodology proposed in HERAG guidance for metals (HERAG fact sheet - assessment of occupational dermal exposure and dermal absorption for metals and inorganic metal compounds; EBRC Consulting GmbH / Hannover /Germany; August 2007).

 

For reference list please refer to endpoint summary of the moieties.

 

Neodecanoate

 

Neodecanoic acid has a low potential for toxicity via the oral and dermal routes. 

 

Oral

Male and female rats were gavaged with neodecanoic acid at concentrations of 1, 1.5, 2, 3, or 4 ml/kg to assess acute oral toxicity.  All animals that died during the study did so within 3 days of exposure. Signs of toxicity included lethargy, hypothermia, piloerection, dyspnea, and ataxia. Based on these results, it is concluded that the LD50 is approximately 2.27 ml/kg (2066 mg/kg). 

 

Dermal

In a study that assessed acute dermal toxicity, male and female rats were exposed to 4 ml/kg (3640 mg/kg) neodecanoic acid via an occluded dermal patch for 24 hours. After 24 hours, the patch was removed and clinical observations were made once daily for 9 days. There were no deaths observed in this study and there were no signs of a toxicity response.  It is concluded that the LD50 is greater than 3640 mg/kg. 

 

 

Fatty acids, C9 -13 neo, potassium salts

Signs of acute oral or acute dermal toxicity are not expected for fatty acids, C9 -13 neo, potassium salts, since the two moieties potassium and neodecanoic acid have not shown signs of acute oral or acute dermal toxicity in experimental testing (both LD50 > 2000mg/kg). Under the assumption that the moieties of fatty acids, C9 -13 neo, potassium salts show their toxicological profile individually upon dissolution, the acute oral and dermal (systemic) toxicity of fatty acids, C9 -13 neo, potassium salts can be calculated using the equation given in regulation (EC) 1272/2008, Annex I, Section 3.1.3.6.1.

A study for acute toxicity via inhalation was not conducted with fatty acids, C9 -13 neo, potassium salts, since it is produced and placed on the market in a form in which no inhalation hazard is anticipated, thus acute toxic effects are not likely to occur during manufacture and handling of that substance. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

 

The calculated oraland dermal LD50 for fatty acids, C9 -13 neo, potassium salts is > 2000mg/kg, hencethe substance is not to be classified according to regulation (EC) 1272/2008 for acute oral and dermal toxicity as well as for specific target organ toxicity, single exposure (STOT SE).

Justification for classification or non-classification

Based on in vivo oral and dermal LD50 data on the moieties, acute toxicity estimates for fatty acids, C9 -13 neo, potassium salts have been calculated resulting in LD50 values > 2000 mg/kg bw.

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptions, fatty acids, C9 -13 neo, potassium salts does neither have to be classified and has no obligatory labelling requirement for acute oral or dermal toxicity nor for specific target organ toxicity after single exposure (STOT SE).