Registration Dossier

Toxicological information

Specific investigations: other studies

Currently viewing:

Administrative data

Endpoint:
specific investigations: other studies
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
hypothesis As a hypothesis, methanol is the critical constituent of the substance (S-Ethanol, composition 2) based on its amount and with regards to its hazardous properties. It is the major constituent affecting the classification and labeling of the target substance (S-Ethanol). Therefore, data from methanol is used in the read-across approach in order to update the hazard assessment of this substance. Other impurities are taken into account for self-classification but there were no need to consider evaluating their properties in hazard assessment because of low concentrations. Analogue approach justification This substance (S-Ethanol, composition 2) has degree of ethanol purity between 76.4-81.9 %. Methanol is the main impurity of the target substance (conc. 13-14 %), and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For chemical safety assessment certain physico-chemical properties are relevant for both human health and environmental health assessment. Also they are important for self-classification and for updating of the exposure assessment of the target substance. For toxicological endpoints, methanol is considered the major drivers for classification and overall safety assessment of the target substance. Therefore, methanol properties were included for chemical safety assessment and the endpoint robust summaries were provided also for methanol.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Folate and 10-formyltetrahydrofolate dehydrogenase in humans and rat retina: Relation to methanol toxicity.
Author:
Martinasevic, M.K. et al.
Year:
1996
Bibliographic source:
Toxicol Appl Pharmacol 141: 373-381
Reference Type:
publication
Title:
Methanol toxicity: Species differences in retinal formate oxidation.
Author:
Eells, J.T. et al.
Year:
1995
Bibliographic source:
Int Toxicol 7: 61

Materials and methods

Principles of method if other than guideline:
The study was designed to determine whether components of folate-dependent formate oxidation, (folate and 10-formyltetrahydrofolate dehydrogenase (10-FDH)) exist in retina and whether differences in these components might explain species-determined susceptibility to methanol intoxication. No methanol was administered.
GLP compliance:
not specified
Type of method:
in vivo
Endpoint addressed:
not applicable

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): no test material; total folate and 10-FDH levels were determined in human and rat retinal tissues.
- Analytical purity: no data

Test animals

Species:
other: rat and human
Strain:
other: rat: Sprague-Dawley
Sex:
not specified

Administration / exposure

Route of administration:
other: no administration
Vehicle:
other: no administration

Results and discussion

Details on results:
The cell-specific localisation of the enzyme, 10-FDH, was found to be similar in rat and human retina, preferentially located in the Müller-cell type, the principal glia of the retina (by immunohistochemistry).
The amount of 10-FDH found in cytosolic as well as in the mitochondrial fraction, was about 3x higher in humans than in rats (Western blot analysis). However, the retinal folate levels were lower in humans (about 14 % of that in rats), compared with the high folate liver pools, the retina contains very much less folate.

Applicant's summary and conclusion