Reaction mass of (2-methoxymethylethoxy)propanol and [2-(2-methoxymethylethoxy)methylethoxy]propanol and sodium methanolate

Repeated dose toxicity: oral

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

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study 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 or test system 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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
100 mg/kg/day
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
500 mg/kg/day
Basis:
actual ingested

Doses / concentrations 3

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.