Saccharomyces cerevisiae cell wall, extracted

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

Executive summary:

Saccharomyces cerevisiae cell walls, extracted, are the concentrated, extracted, insoluble component obtained from yeast biomass produced according to common yeast production as described above.

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 normally healthy individuals. This indicates that humans are in constant contact with these yeasts. S. cerevisiae is recognised at EU level as food and feed additives, 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 limited amount of water-soluble material (only around 13% of soluble material, expressed as carbon, with a loading rate of 10 g/L of substance). As a reminder, the substance if mainly constituted of cell membranes, with a particle size distribution ranging from c.a. 20µm (D10) to c.a. 120 µm (D90), with a masss median aerodynamic diameter of c.a. 60 µm. This implies that the partition coefficient octanol/water is not applicable and cannot be used to anticipate the behaviour of the registered substance. Although the molecular weight is not applicable, the 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 can undergo either by pinocytosis or by digestion of the particles followed by absorption of the nutrients. Absorption by dermal route is not anticipated due to the physical nature of the substance. And the same is expected for inhalation exposure as the particle size distribution shows that only a very small fraction of the substance (D10= c.a. 20 µm).

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, 2020, Klimisch 1). This is confirmed in a Klimish 4 feeding study, with rats given up around 4000 mg/kg bw/d (corrected from bodyweight and food consumption) during 28 days. In this sub-acute repeated dose study, no effects were recorded. More reliable data are available for an analogue substance, Saccharomyces cerevisiae, lysate. This analogue substance, is the whole yeast cells when the registered substance is limited to the cell walls, the less bioavailable part of the analogue substance. In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422, Klimisch 1) this study 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 fix a NOEL 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 the analogue substance, and no effects were seen.

Acknowledging that the registered substance is an UVCB with very complex chemical structures, mainly proteins and sugars, metabolisation can not 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, Klimisch 1), metabolic activation didn’t influence the concentration where cytotoxicity has been observed (500 µg/plate). And in the micronucleus test (OECD 487, Klimisch 1), cytotoxicity is detected at a slightly lower concentration without metabolic activation (150-200 %g/mL versus 250 µg/mL).

In conclusion, the registered substance is not anticipated to be absorbed by dermal or inhalation route. In case oral absorption route occurs, it might be via pinocytosis or digestion/absorption of nutrients. Metabolisation of the whole substance, not only the fraction likely to be absorbed, might reduce its biological activity. Anyhow, no signs of toxicity have been reported up to 1000 mg/kg bw/d for a reliable analogue 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 route. In case oral absorption route occurs, it might be via pinocytosis or digestion/absorption of nutrients. Metabolisation of the whole substance, not only the fraction likely to be absorbed, might reduce its biological activity. Anyhow, no signs of toxicity have been reported up to 1000 mg/kg bw/d for a reliable analogue substance. All this set of information is coherent with the current use of yeast cells as food/feed additives.