Saccharomyces cerevisiae, lysate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

other: Weight of evidence based on available information

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Conclusions:

In conclusion, the registered substance is not anticipated to be absorbed by dermal or inhalation routes. Oral absorption of nutrients from the soluble part is expected. In case oral absorption of insoluble fraction occurs, it might be via pinocytosis or digestion/absorption of nutrients. Metabolization of the whole substance, not only the fraction likely to be absorbed, is not expected to influence its biological activity and no signs of toxicity have been reported up to 1000 mg/kg bw/day of Saccharomyces cerevisiae, lysate substance. All this set of information is coherent with the current use of yeast cells as food/feed additives.

Executive summary:

There are no studies available in which the toxicokinetic behaviour of “Saccharomyces cerevisiae, lysate” has been investigated. Therefore, the assessment of Toxicokinetics of Saccharomyces cerevisiae, lysate is performed on a qualitative basis taking into account the available information on substance definition as well as physicochemical and toxicological characteristics according to Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2008).

Saccharomyces cerevisiae, lysate is the concentrated, non-extracted, partially soluble digest obtained from yeast biomass produced according to common yeast fermentation process. The lysis of yeast cells results in both soluble and insoluble components (cell walls).  Saccharomyces cerevisiae, lysate is composed primarily of amino acids, peptides, proteins, carbohydrates, lipids and different mineral salts. The soluble fraction represents between 20-90% of this UVCB substance.

S. cerevisiae is a commonly used industrial microorganism and is ubiquitous in nature, being present on fruits and vegetables. Industrial workers and the general public come into contact with S. cerevisiae on a daily basis through both inhalation and ingestion. Saccharomyces spp. are frequently recovered from the stools and throats of normal healthy individuals. This indicates that humans are in constant contact with these yeasts. S. cerevisiae is recognised at EU level as food and feed additive, as well as novel food. There are individuals who may ingest large quantities of S. cerevisiae every day, for example, people who consume yeast as part of a "health food" regimen. Therefore, studies were conducted to ascertain whether the ingestion of large numbers of these yeasts might result in either colonization, or colonization and secondary spread to other organs of the body. S. cerevisiae is not considered a pathogenic microorganism. Yeast has been used for centuries as a leavening for bread and fermenter of beer without records of virulence.

The registered substance is an UVCB substance, with a water-soluble fraction between 20-90% (expressed as carbon, with a carbon content of 104.9 mg carbon/L with 0.59 RSD% in case of preparation 1 g/L nominal loading rate). The insoluble part (10-80%) is constituted of cell membranes.

Due to the complex composition of the substance Saccharomyces cerevisiae, lysate, it is not feasible to determine its partition coefficient experimentally and QSARs calculations are not possible due to the complex composition and the unknown precise structure of the constituents. Even the estimation of log Kow based on the solubility in water and in n-octanol is technically not feasible. Thus, the partition coefficient octanol/water cannot be used to anticipate the behaviour of the registered substance.

The molecular weight is not applicable for the substance. At least, the insoluble fraction (yeast cell wall fractions) can be assumed to be large enough to make absorption less favourable. However, yeast particles might be taken up by pinocytosis. Therefore, it is concluded that oral absorption of the insoluble fraction can undergo either by pinocytosis or by digestion of the particles followed by absorption of the nutrients. Oral absorption of nutrient constituents from the soluble fraction is highly expected (amino acids, peptides, minerals, etc).

Absorption by dermal route is not anticipated due to the physical nature of the substance. Dry particulates are taken up less readily than liquids. Dry particulates will have to dissolve into the surface moisture of the skin before uptake can begin. Furthermore, Saccharomyces cerevisiae, lysate substance is not irritating or corrosive to skin (property which may enhance skin penetration) and showed no signs of systemic toxicity following acute dermal exposure.

The same is expected for inhalation exposure. Indeed, the low vapour pressure (low volatility substances have a vapour pressure of less than 0.5 KPa), indicates that it is not likely that Saccharomyces cerevisiae, lysate vapours (determined to be 4.60 x 10-2 Pa at 20 °C) will reach the nasopharyngeal region or subsequently the tracheobronchial or pulmonary region. In addition, the high mass median aerodynamic diameter (400 µm) prevents particles to be inhaled, as these have an aerodynamic diameter higher than 100 μm. The particle size distribution shows that only a very small fraction of the substance (D10 = c.a. 43 µm) has an aerodynamic diameter less than 100 μm. Therefore, Saccharomyces cerevisiae, lysate absorption by inhalation route is not anticipated.

Anyhow, even if oral absorption cannot be ruled out, the available data on toxicological parameters show the lack of toxicity. No effects at all (mortality, clinical signs, bodyweight, necropsy) were recorded when exposed to 2000 mg/kg bw/d in a single dose (OECD TG 423, GLP, 2017, Klimisch 1). A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422, 2018, Klimisch 1) did not result in test item related mortality, clinical signs, or significant changes in body weight / body weight gain, food consumption, haematology, clinical chemistry or urinalysis parameters. No test item related effect was detected during neurotoxicity assessment. No test item-related macroscopic or microscopic findings were recorded in any of the dose groups at necropsy or during histopathology evaluation, leading to set a NOAEL at 1000 mg/kg bw/d. In the range finder ran for this study, rats were given up to 2000 mg/kg bw/d during 7 days of Saccharomyces cerevisiae, lysate substance, and no effects were seen.

Acknowledging that the registered substance is an UVCB with very complex chemical structures, mainly proteins and sugars, metabolization cannot be predicted. However, the in vitro genotoxicity studies can be informative on the role of Phase I enzymes in the behaviour of the substance. In the Ames test (OECD 471, 2018, Klimisch 1), metabolic activation didn’t influence at all the cytotoxicity as no cytotoxicity was observed in any strain up to the highest concentration recommended by the guideline (i.e., 5000 µg/plate). The same result was obtained in the in vitro micronucleus test (OECD 487, 2018, Klimisch 1) and the in vitro gene mutation study in mammalian cells (OECD 487, 2018, Klimisch 1), where metabolic activation had no influence on cytotoxicity of the substance up to the highest achievable dose level and taking into account the level of precipitate, respectively.

In conclusion, the registered substance is not anticipated to be absorbed by dermal or inhalation routes. Oral absorption of nutrients from the soluble part is expected. In case oral absorption of insoluble fraction occurs, it might be via pinocytosis or digestion/absorption of nutrients. Metabolization of the whole substance, not only the fraction likely to be absorbed, is not expected to influence its biological activity and no signs of toxicity have been reported up to 1000 mg/kg bw/day of Saccharomyces cerevisiae, lysate substance. All this set of information is coherent with the current use of yeast cells as food/feed additives.

Description of key information

The registered substance is not anticipated to be absorbed by dermal or inhalation routes. Oral absorption of nutrients from the soluble part is expected. In case oral absorption of insoluble fraction occurs, it might be via pinocytosis or digestion/absorption of nutrients. Metabolization of the whole substance, not only the fraction likely to be absorbed, is not expected to influence its biological activity and no signs of toxicity have been reported following subacute repeated exposure up to 1000 mg/kg bw/day of Saccharomyces cerevisiae, lysate substance. All this set of information is coherent with the current use of yeast cells as food/feed additives