Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: assessment based on available information
Adequacy of study:
key study
Study period:
October 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study is based on expert judgement. Non GLP assessment report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Objective of study:
other: toxicokinetic assessment
Test guideline
Qualifier:
no guideline required
Deviations:
not applicable
Principles of method if other than guideline:
A theoretical approach of the toxicokinetic properties of the substance based on the available physicochemical properties and toxicological data.

GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Any other information on results incl. tables

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. 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. It was found that the installation of very large numbers of S. cerevisiae into the colons of animals would result in both colonization and passage of the yeasts to draining lymph nodes. It required up to 1010 S. cerevisiae in a single oral treatment to rats to achieve a detectable passage from the intestine to the lymph nodes. The concentrations of S. cerevisiae required were well beyond those that would be encountered through normal human daily exposure. S. cerevisiae is not considered a pathogenic microorganism. There is an extensive history of use of and exposure to S. cerevisiae with a very limited record of adverse effects to the environment or human health. Yeast has been used for centuries as a leavening for bread and fermenter of beer without records of virulence.

Only limited physicochemical properties are available for Springer 0207/0-MG-L. The high water solubility of >200 g/L favours oral absorption. Although the partition coefficient cannot be determined, it is considered to be favourable for oral absorption (<4). Although the molecular weight is not applicable, the yeast cells can be assumed to be large enough to make absorption less favourable. However, yeast particles might be taken up by pinocytosis. Therefore, for risk assessment purposes the oral absorption is set at 10%. The results from the toxicity studies do not provide reason to deviate from this proposed oral absorption.

Springer 0207/0-MG-L is not expected to have a high vapour pressure (measured vapour pressure on aqueous extract) indicating that it is not likely that vapours will reach the nasopharyngeal, tracheobronchial or pulmonary region. In addition, 92% of the particles is larger than 50 µm, of which most are between 50 and 125 µm, indicating particles will deposit in the nasopharyngeal region and subsequently be coughed or sneezed out of the body or swallowed. The limited amount of particles <50 µm present might reach the tracheobronchial region and particles <15 µm might reach the pulmonary region. Based on the high water solubility Springer 0207/0-MG-L will dissolve in the mucus lining of the respiratory tract and a log Pow >0 indicates a potential for absorption directly across the respiratory tract epithelium. Subsequent absorption through pores is not likely taking into account the size of the particles. However, small amounts may be taken up by phagocytosis and transported to the blood via the lymphatic system. Overall, it is concluded that when Springer 0207/0-MG-L is inhaled (particles <50 µm), some absorption is expected and for risk assessment purposes the inhalation absorption is set at 10%.

Although the high water solubility and partition coefficient <4 favour dermal absorption, the large particle size (cells) disfavours dermal uptake. The criteria for 10% dermal absorption as given in the REACH guidance (molecular weight >500 and log Pow >4) are not met and hence 100% dermal absorption should be proposed. However, it is generally accepted that dermal absorption is lower or equal to oral absorption. Therefore, for risk assessment purposes the dermal absorption is set at 10%.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: oral, dermal and inhalation absorption are set at 10%
For risk assessment purposes the following absorption factors were derived:
oral absorption factor: 10%
dermal absorption factor: 10%
inhalation absorption factor: 10%
Executive summary:

For risk assessment purposes the following absorption factors were derived:

oral absorption factor: 10%

dermal absorption factor: 10%

inhalation absorption factor: 10%