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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study on methanol is relevant to the repeat dose toxicity of sodium methanolate. Humans are known to be more sensitive than rodents to the toxicity of methanol.

Data source

Reference
Reference Type:
other: USEPA study and IRIS summary
Title:
Rat oral subchronic toxicity study with methanol.
Author:
USEPA
Year:
1986
Bibliographic source:
United States Environmental Protection Agency, Office of Solid Waste, Washington, DC.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Not available

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
No details were available

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Rats were gavaged daily with 0, 100, 500, or 2500 mg/kg/day of methanol. Six weeks after dosing, 10 rats/sex/dose group were subjected to interim sacrifice while the remaining rats continued on the dosing regimen until the final sacrifice (90 days).
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90-days
Frequency of treatment:
once/day
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
100 mg/kg/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
500 mg/kg/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
2500 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
30
Control animals:
yes, concurrent vehicle
Details on study design:
Sprague-Dawley rats (30/sex/dose) were gavaged daily with 0, 100, 500, or 2500 mg/kg/day of methanol. Six weeks after dosing, 10 rats/sex/dose group were subjected to interim sacrifice while the remaining rats continued on the dosing regimen until the final sacrifice (90 days).
Positive control:
None

Examinations

Observations and examinations performed and frequency:
This study generated data on weekly body weights and food consumption, clinical signs of toxicity, ophthalmological evaluations, mortality, blood and urine chemistry, and gross and microscopic evaluations.
Sacrifice and pathology:
Gross and histopathology
Other examinations:
* opthalmic examination
* blood chemistry
* urinalysis
Statistics:
Not described

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
There were no differences between dosed animals and controls in body weight gain, food consumption, gross or microscopic evaluations. Elevated levels of SGPT, SAP, and increased, but not statistically significant, liver weights in both male and female rats suggest possible treatment-related effects in rats dosed with 2500 mg methanol/kg/day despite the absence of supportive histopathologic lesions in the liver. Brain weights of both high-dose group males and females were significantly less than those of the control group. Based on these findings, 500 mg/kg/day of methanol is considered a NOAEL in rats.

Effect levels

Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: Brain weight decrease, elevated SGPT and SAP in absence of liver weight or histopathology

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Based on these findings, 500 mg/kg/day of methanol is considered a NOAEL in rats.
Executive summary:

Sprague-Dawley rats (30/sex/dose) were gavaged daily with 0, 100, 500, or 2500 mg/kg/day of methanol. Six weeks after dosing, 10 rats/sex/dose group were subjected to interim sacrifice while the remaining rats continued on the dosing regimen until the final sacrifice (90 days).

There were no differences between dosed animals and controls in body weight gain, food consumption, gross or microscopic evaluations. Elevated levels of SGPT, SAP, and increased, but not statistically significant, liver weights in both male and female rats suggest possible treatment-related effects in rats dosed with 2500 mg methanol/kg/day despite the absence of supportive histopathologic lesions in the liver. Brain weights of both high-dose group males and females were significantly less than those of the control group.

Based on these findings, 500 mg/kg/day of methanol is considered a NOAEL in rats.