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Toxicological information

Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
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:
Sperm count, morphology, and fluorescent body frequency in autopsy service workers exposed to formaldehyde.
Author:
Ward, J. B. et al.
Year:
1984
Bibliographic source:
Mutat Res 130: 417-424

Materials and methods

Principles of method if other than guideline:
Male mice were treated orally with methanol and maintained without exposure for 5 weeks. Sperm morphology was examined.
GLP compliance:
not specified
Type of method:
in vivo

Test material

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

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratory, Portage, MI
- Age at study initiation: 4-month old

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
no data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
5 consecutive days
Frequency of treatment:
daily
Duration of test:
5 days (with exposure) + 5 weeks (without exposure)
Doses / concentrations
Remarks:
Doses / Concentrations:
1000 mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Statistics:
The effects of exposure and non-exposure for each factor were compared by Student´s t-test.
Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) [Nie et al., 1975].

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
< 1 000 mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
other: sperm morphology

Observed effects

In the methanol-treated animals, a slight, but statistically insignificant increase in sperms abnormalities (1.86 +-0.91 % vs. 1.12 +-0.39 % in the water control) was observed, while the treatment with cyclophoshamide (100 mg/kg) resulted in an about 5-fold increase (5.84 +-1.94).

Applicant's summary and conclusion