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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
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

Reference
Reference Type:
publication
Title:
Circulating concentrations of testosterone, luteinizing hormone and follicle stimulating hormone in male rats after inhalation of methanol.
Author:
Cameron, A.M. et al.
Year:
1984
Bibliographic source:
Arch Toxicol Suppl 7: 441-443

Materials and methods

Principles of method if other than guideline:
Investigation of sexual hormone status in male mature rats after subacute exposure to methanol vapours.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): methanol, no further data
- Analytical purity: no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged (no vehicle)
Remarks on MMAD:
MMAD / GSD: not applicable
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
1, 2, 4 or 6 weeks
Frequency of treatment:
8 h/d, 5 d/wk
Doses / concentrations
Remarks:
Doses / Concentrations:
0.265, 2.65, 13.3 mg/L (corresponding to 200, 200, 10000 ppm)
Basis:
nominal conc.
No. of animals per sex per dose:
no data
Control animals:
yes, concurrent no treatment
Positive control:
not applicable

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEC
Effect level:
2.65 mg/L air
Sex:
male
Dose descriptor:
LOAEC
Effect level:
13.3 mg/L air
Sex:
male
Basis for effect level:
other: significant increase in circulating LH after 6 wks of exposure

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Significantly decreased levels of circulating free testosterone were observed among rats exposed at 200 ppm for 2 and 6 weeks (32 % of control) and 6 weeks at 2,000 ppm. The high dose group (10,000-ppm) showed no change. The authors interpreted this as evidence that methanol exposure had lowered testicular production of testosterone. In addition, significant increases in circulating LH were observed after six weeks of exposure to 10,000 ppm. No changes in follicle stimulating hormone levels were observed.

Conclusion: Results were contradictory because LH increases, but testosterone shows a negative trend.

Applicant's summary and conclusion