Butanone

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From Apr. 21, 1979 to May 24, 1979

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented, according to accepted guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

no

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butanone

EC Number:

201-159-0

EC Name:

Butanone

Cas Number:

78-93-3

Molecular formula:

C4H8O

IUPAC Name:

butan-2-one

Details on test material:

- Name of test material (as cited in study report): Methyl ethyl ketone
- Analytical purity: 99.605 %
- Lot/batch No.: 36799

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Spartan Research Animals, Haslett, Michigan
- Age at study initiation: Reported as adult
- Weight at study initiation: 250 g
- Fasting period before study: None
- Housing: Individuall housed in stainless steel, wire-bottom cages. (group housed in exposure chambers for 7 hours/day during exposure period)
- Diet (e.g. ad libitum): Commercial laboratory chow (Ralston Purina company).
- Water (e.g. ad libitum): ad libitum when not in exposure chamber
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (F): 70 ± 3 F
- Humidity (%): 45 ± 5%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: Not reported

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

whole body

Vehicle:

other: airstream

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:exposure cage
- Method of holding animals in test chamber: cage
- Source and rate of air: filtered air
- Method of conditioning air: Not reported
- System of generating particulates/aerosols: Not aplicable
- Temperature, humidity, pressure in air chamber: Not reported
- Air flow rate: Not reported
- Air change rate: Not reported
- Method of particle size determination: Not aplicable
- Treatment of exhaust air: Not reported


TEST ATMOSPHERE
- Brief description of analytical method used:
- Samples taken from breathing zone: yes


VEHICLE (if applicable)
- Justification for use and choice of vehicle:Filtered air
- Composition of vehicle:Filtered air
- Type and concentration of dispersant aid (if powder): Not applicable
- Concentration of test material in vehicle: 400, 1000, or 3000 ppm
- Lot/batch no. of vehicle (if required): Not applicable
- Purity of vehicle:not reported

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Chamber concentrations monitored 15 min/hr/chamber using Miran I Variable Filter Infrared Analyzer.

Details on mating procedure:

- Impregnation procedure: purchased timed pregnant
- If cohoused:not reported (bred by supplier)
- M/F ratio per cage: not reported (bred by supplier)
- Length of cohabitation: not reported (bred by supplier)
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility: not reported (bred by supplier)
- Further matings after two unsuccessful attempts: not reported (bred by supplier)
- Verification of same strain and source of both sexes: not reported (bred by supplier)
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy

Duration of treatment / exposure:

Day 6 through day 15 of gestation

Frequency of treatment:

Daily, 7 hours/day

Duration of test:

18 days

No. of animals per sex per dose:

25 females/group, 35 females/control group

Control animals:

other: Filtered room air

Details on study design:

- Dose selection rationale: Based on previous teratologic studies
- Rationale for animal assignment (if not random): Random

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: At day 21 of gestation


BODY WEIGHT: Yes
- Time schedule for examinations: Day 6, 8, 10, 16 and 21 of gestation


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Not a feeding study


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not a drinking water study


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21
- Organs examined: Liver

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes
- Number of early resorptions: only in non-pregnant animals.
- Number of late resorptions: Not specified

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: all per litter
- Head examinations: Yes: 1/3 per litter

Statistics:

The frequency of alterations and resorptions among litters and the fetal population was evaluated by the Wilcoxon test. Other incidence data were analyzed by the Fisher exact probability test. Analysis of body weights, liver weights and body measurements were made by analysis of variance. Group means were compared to control values using Dunnett's test.

Indices:

Not reported

Historical control data:

Not reported

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Maternal body weights were significantly decreased on day 16 and a decrease in maternal body weight gain occured on days 10 through 15 in rats exposed to 3000 ppm of MEK. Water consumption of rats exposed to the high dose level of MEK was significantly increased on days 15 through 17 of gestation

Effect levels (maternal animals)

Dose descriptor:

NOAEC

Effect level:

ca. 1 002 ppm (analytical)

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
Significant decrease in delayed ossification of interparietal bones and significant increase in the incidence of extra lumbar ribs at 3000 ppm.

Effect levels (fetuses)

Dose descriptor:

NOAEC

Effect level:

ca. 1 002 ppm (analytical)

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified