2-methylbut-3-en-2-ol

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: An international/national standard method is not mentioned in the report, but no relevant deviations compared to the OECD407 were found

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

not specified

Principles of method if other than guideline:

-

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methylbut-3-en-2-ol

EC Number:

204-068-4

EC Name:

2-methylbut-3-en-2-ol

Cas Number:

115-18-4

Molecular formula:

C5H10O

IUPAC Name:

2-methylbut-3-en-2-ol

Test animals

Species:

rat

Strain:

other: Fü-Albino rats (RORO)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:

Basis:
nominal in water

No. of animals per sex per dose:

groups of 10 -14 male and 10-14 female rats per dose

Control animals:

yes

Results and discussion

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

ca. 50 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: clinical signs

2

Dose descriptor:

LOEL

Effect level:

>= 200 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No toxicologically relevant changes were seen in the animals treated with 50 mg/kg/day.

In mid dose females (200 molko/dav), minimally increased liver weights and hypertrophy of hepatocytes (1 F) were observed. In mid dose males, the kidney weights were minimally increased and slight to moderate accumulation of renal hyaline droplets were noted.

The high dose of 600 mq/kq/dav induced sedation, ataxia and uncoordinated gait during the first days of treatment. Salivation was minimally increased after repeated administrations. Two animals (1 M, 1 F) died spontaneously. Since no apparent cause of death was determined, a treatment-related effect cannot be excluded.

No relevant changes in hematological parameters, in ophthalmoscopy and urine analyses were noted.

Salient findings were confined to the liver of males and females and to the kidneys of male rats.

In males and females, minimally increased liver weights and periacinar hypertrophy of hepatocytes were observed. Transaminases were minimally increased. In male rats minimal increases in kidney weights and tubular accumulation of hyaline droplets were observed. No functional disturbances of the kidneys were noted. a2y-Globulin accumulation in male rats is a species and

sex-specific finding and not considered to be of predictive value for humans.

Applicant's summary and conclusion

Conclusions:

It can be concluded that high doses of methylbutenol lead to slightly increased liver weights, minimally increased transaminases and hypertrophy of hepatocytes being reversible upon cessation of treatment, thus, suggesting liver enzyme
induction. Methylbutenol induced CNS-stimulated clinical symptoms, such as ataxia, uncoordinated gait, hypersalivation.

Executive summary:

In the 4-week oral toxicity study in rats, the no observed effect level (NOEL) of

methylbutenol was 50 mg/kg body weight per day. As the adverse effects seen in

the high dose group were only minimally expressed in mid dose animals, the dose

of 200 mg/kg body weight per day is considered the low observed effect level

(LOEL).