2,4-dimethylpentan-3-one

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

May, 1981

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

other: Toxic Substances Control Act Test Guidelines (Environmental Protection Agency, September 27, 1985, and revised guidelines 52 FR 19056)

Version / remarks:

May 20, 1987

Test guideline 3

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

September, 1984

GLP compliance:

yes

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dimethylpentan-3-one

EC Number:

209-294-7

EC Name:

2,4-dimethylpentan-3-one

Cas Number:

565-80-0

Molecular formula:

C7H14O

IUPAC Name:

2,4-dimethylpentan-3-one

Test material form:

liquid

Details on test material:

- Name of test material (as cited in report): 2,4-Dimethylpentanon-3 / Diisopropyl keton
- Physical state: liquid

Specific details on test material used for the study:

- Name of test substance( as cited in report): Diisopropyl ketone; 2,4-Dimethyl-3-pentanone; DIPK
- Purity: 100 ± 0.00% (mean ± SD)

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Kingston, NY
- Age at study initiation: Males 41 days, Females 52 days
- Weight at study initiation: Males 189 ± 11 g, Females 172 ± 10 g (mean ± SD)
- Housing: Singly housed in multicompartmented stainless steel mesh cages
- Diet: Certified Rodent Diet (Agway Prolab RMH-3000, pellets), ad libitum during non-exposure periods
- Water: ad libitum during non-exposure periods

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1 - 23.3 (reported as 70-74 °F)
- Humidity (%): 52 - 56
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

The inhalation exposures were conducted in 420 L stainless steel and glass inhalation chambers at target concentrations of 1250 and 2500 ppm. There was no control group used in this study. The chambers were maintained at pressures of -0.25 and -0.50 inch water (gauge) relative to room air for the low and high-exposure groups, respectively, and at 12 air changes per hour. Male and female rats were singly housed and exposed simultaneously for six hours in the same inhalation chamber.

A vapor was produced by metering the test substance from a reservoir into a glass bead-packed column where it evaporated. The column was supplied with metered, dried, oil-free compressed air. The resultant vapor was directed into the turret of the chamber where it was mixed with filtered, conditioned air. Chamber vapor concentrations were analytically determined 16 times during the exposure by infrared spectroscopy. The samples were taken from a fixed reference position in the inhalation chamber. Chamber temperature and relative humidity were recorded twice per hour. Chamber air flow was set at 84 liters per minute. The nominal chamber concentration was calculated from the mass of chemical consumed and air flow. The concentration of background nongaseous material relative to chamber air and room air was measured twice for each chamber during the exposure to ensure that the exposures were to a vapor and not an aerosol. The concentration of the test substance vapor was measured during a pre-study test, from various positions within the inhalation chamber, to assess the homogeneity of the vapor throughout the chamber.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

6 h

Concentrations:

1462 and 2765 ppm (analytical)
1250 and 2500 ppm (target)
1579 and 4650 ppm (nominal)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body weights were measured on Days 0, 2, 7, and 14.
Rats visible through chamber windows were observed for clinical signs during exposure. Before and after exposure and on days of body weight measurement, each rat was removed from its cage and examined by a trained technician. Every workday afternoon and on mornings when body weights were not collected, cage side observations were conducted. Observations included, but were not limited to, examination of behavior pattern, motor activity, respiratory patterns, hair, skin, eyes, feces and urine. Animals were checked for mortality on weekends.

- Necropsy of survivors performed: yes
Rats were fasted overnight prior to necropsy on Day 15, anesthetized with C02, and exsanguinated by severing the posterior vena cava.
The following organs were examined during the necropsy: nasal passages, trachea, lungs, heart, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, pancreas, liver, salivary glands, kidneys, urinary bladder, pituitary gland, adrenal glands, thyroid glands, parathyroid glands, thymus, spleen, mesenteric lymph nodes, bone marrow (femoral), brain, testes, epididymides, male accessory sex glands, ovaries, vagina, uterus, and Fallopian tubes.

Statistics:

Mean values were calculated for test substance concentration, chamber temperature, chamber relative humidity, and body weight

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2 765 ppm

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: reversible narcotic effects and lacrimation

Mortality:

No mortality occurred during the course of this study.

Clinical signs:

other: During the exposure, the high-exposure group exhibited severe narcosis and moderate dyspnea, and the low-exposure group exhibited moderate lethargy and minor dyspnea. Immediately after the exposure, all male and female animals from the high exposure group

Body weight:

A very slight body weight loss was observed at both the high-exposure (5/5 males, 3/5 females) and low-exposure levels (2/4 males, 3/5 females) at the Day 2 body weight determination. Subsequently, all animals, except one (Rat 2, low-exposure group), appeared to gain weight normally. Rat 2 exhibited a slight body weight loss at Day 2 apparently due to reduced water intake. This animal was provided with a water bottle, and subsequently recovered. The percent weight gain between Day 0 and 14 for male and female animals were, respectively, +56% and +26% for the high-exposure group and +60% and +22% for the low-exposure group. For the male animals from both exposure levels, this represented a slightly lower weight gain than is commonly seen in rats of this age and strain, although it did not follow a concentration-dependent pattern. Mean terminal body weights for male and female rats from the high- and low-exposure levels were comparable.

Gross pathology:

There were no exposure-related changes detected on gross examination of male or female rats exposed to the test material. No tissue was collected for microscopic examination.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met