Registration Dossier

Administrative data

Description of key information

The high solubility, low Kow and ionic character of potassium sodium tartrate predict that it will be absorbed very poorly across the skin. This together with its proven low oral toxicity and supporting information of absence of toxicity in skin irritation studies performed in rabbits point to very low hazard associated to dermal exposure and thereby do not warrant the execution of a dermal toxicity test.

Long term worplace exposure (> 6 months) inhalatory LD50 can be assumed to be well above 4.5 mg/m3. A case study in tin manufacturing plant reveales dental erosion of workers at concentrations of the order of 4.5 mg/m3.  

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
3 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
discriminating conc.
4.5 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
3 000 mg/kg bw

Additional information

Oral toxicity

An acute LD10of 4.37 g per kg for sodium tartrate [isomer not stated but probably L(+)] given orally was determined for mixed strain white mice by Locke et al. In the animals succumbing to the treatment, the intestines were distended with fluid. Ninety percent of the deaths occurred within 24 hours of dosing; there was an average weight loss of 8 percent in the animals surviving the treatment. An approximate LD 50 in the vicinity but greater than 6.6 g/kg seems apparent from the study. In this same study, an LD0 of 3.68 g per kg for sodium tartrate given orally was determined for white New Zealand rabbits. An approximate LD 50 in the vicinity of 5.3 g/kg seems apparent from the study. In both cases results are to be viewed with caution, as experimental design, quality of animals and duration of observations do not correspond to current standards, however, considering mortality in acute studies tend to occur in the first days after exposure, the studies reported provide useful insight to the low acute oral toxicity of disodium tartrate, which is equally applicable to analogue potassium sodium tartrate.

There are numerous supporting studies, of dubious reliability which indicate LD50s for sodium salts of tartaric acid, and for tartaric acid itself, of several g/kg in dogs, cats and rabbits after oral dosages.

In addition a reliable peer-reviewed study by Down el al (1977) performed for toxicokinetic purposes offers valuable insight into the acute toxicity of L(+) monosodium tartrate administered for 7 consecutive days to rats by oral gavage at a single daily dose o 2.37 mg/kg. No mortality or adverse effect was observed giving a reliable indication that LD50 of sodium and potassium tartrate salts L(+) form is above 2.7 mg/kg.

Given that there is ample evidence of LD50 well above 2.7 g/kg in rat and in the vicinity of 5 g/kg in rabbits and mice, a conservative value of 3.0 mg/kg is proposed and used in this ESS.

Dermal toxicity

Potassium sodium tartate, like other potassium or dodium salts of tartaric acid has very low Kow, a very high water solubility (> 100 g/L) and is is mostly ionised at phisiological pH. According to the description made in section 7.1. and to the indication in part 7a of the CSR Guidance Document, passage through the stratum corneum of the skin of this substance is very unlikely. Taking into account that the substance has very low toxicity and is rapidly degraded or excreted, the performance of dermal toxicity tests is not warranted. In addition, and as supported information, no toxic effect whatsoever was appreciated after dermal exposure of two rabbits to a single dose of 0.5 g/ animal for a total of 4 hours. Thereby it is not considered justified to perform a dermal toxicity test, although it is recognised that dermal exposure during manufacture and handling cannot be excluded.

Inhalation toxicity

The MMAD of the worst-case commercial granular presentations of the product lies between 73.4 and 88.5 µm, well above the fraction fraction known as respirable, that may reach the lower respiratory tract. Although a maximum of 4.14% of the substance in the granular solid corresponds to particles with a diameter below 10 µm, and almost 50% of the total particles have a diameter below 100 microns, it is considered that in the event of exposure to dust, the majoruty of the substance will be retained in the mouth and upper airways, being refluxed into the digestive system. The very low oral toxicity of the substance, its non classification as an eye or dermal irritant and supporting occupational exposure studies which do not indicate respiratory problems or toxicity even at high dust exposures (see corresponding sections in dossier and CSR) do not justify in vivo inhalation toxicity testing of this substance.

Thereby based on the fact that the test substance has very low vapor pressure and high melting point, that its potential for generation of inhalable forms is low and that the identified uses of this substance will not result in significant aerosols or particles of an inhalable size, exposure to humans via the inhalatory route will be unlikely to occur, and no acute inhalation test was performed

This is futher supported by a human case study. Said report focuses on effects of tartaric acid (and combined tartrates) which are inhaled and presumably retained in the mouth and upper respiratory tract. This leads to severely acidic saliva which on long term exposure leads to teeth erosion with progressive disappearance of the enamel and exposure of the dentine, leading to the eventual loss of the pieces.

Long term worker exposure to free tartaric acid and combined tartaric acid dust in conditions of high dustiness (ca. 4.5 mg/m3) for periods of 30 h/week for more than 6 months result in teeth erosion and progressive loss of dental pieces, but other clinical signs, morbidity or lethality are reported in a case study involving 15 youg females exposed in a tin-making company. Thereby the long term LD50 can be assumed to be well above 4.5 mg/m3. This case study is considered relevant towards supporting the low inhalatory toxicity of tartaroc acid and furthermore of combined tartaric acid, such as in the form of potassium sodium tartrate.

Justification for classification or non-classification