Propyloxirane

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

repeated dose toxicity: inhalation

Remarks:

combined repeated dose and carcinogenicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well-documented report, comparable to guideline/standards

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Principles of method if other than guideline:

according to NTP-internal guidelines

GLP compliance:

yes

Remarks:

testing lab.

Test material

Test material information

Constituent 1

Reference substance name:

1,2-epoxybutane

EC Number:

203-438-2

EC Name:

1,2-epoxybutane

Cas Number:

106-88-7

Molecular formula:

C4H8O

IUPAC Name:

2-ethyloxirane

Details on test material:

purity: > 99%

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female rats were obtained from Charles River Breeding Laboratories, observed for 20-21 days, and assigned to groups according to tables of random numbers. Feed was available ad libitum during non-exposure periods; water was, available at all times.
Age when placed on study: 7-8 wk.
Identification: ear tag
Stainless steel wire bottom cages
Animal room environment: Temperature 73-76°F during exposure; humidity 46%-55% during exposure; fluorescent light 12h/d; 10 room air changes during exposure, 20 room air changes/h during non-exposure period

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: room air

Details on inhalation exposure:

The liquid to be vaporized was contained in a 1.6-liter stainless steel reservoir housed in a vapor hood in the exposure room. The liquid was pumped from this reservoir to a stainless steel cylinder covered with a glass fiber wick from which the liquid was vaporized. An 80-watt heater and a temperature-sensing element were incorporated within the cylinder. The heater maintained the vaporizer at approximately 58°C. The surface temperature of the vaporizer was slightly lower. To minimize material loss due to condensation on duct walls, each cylindrical vaporizer was positioned in the fresh air duct leading directly into the exposure chamber.
Uniformity of vapor concentration in each exposure chamber was measured with a portable photoionization detector periodically throughout the studies. The data showed that when expressed as a percentage of the normalized average concentration of all 12 sampling positions, the standard deviation did not exceed 5% for all but two measurements. (For those two measurements, the standard deviation was within 10%.)
Samples of the atmosphere in the 1,2-epoxybutane exposure chamber were examined for the occurrence of potential degradation products, specifically 1,2-butandiol. Through the use of a Hewlett Packard model 5840A gas chromatograph equipped with a flame ionization detector and a 6 ft x 4 mm 1D glass column packed with 10% Carbowax 20M on 801100 Chromosorb WAW, a single homogeneous peak was observed; no evidence for any degradation was detected. It is concluded from this study that the 1,2-epoxybutane vapor generated during these studies was at least 99% pure.

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

6 hours per day, 5 days per week (65 exposures)

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 100, 200, 400, or 800 ppm (= 0.15, 0.30, 0.60, 1.18, 2.39 mg/l)
Basis:
nominal conc.

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

Animals were checked twice per day; moribund animals were killed. Individual animal weights were recorded weekly.

Sacrifice and pathology:

At the end of the 13-week studies, survivors were killed. A necropsy was performed on all animals except those excessively autolyzed or cannibalized.
Necropsy performed on all animals; all controls and the two highest dose groups examined histologically. Tissues examined: adrenal glands, brain, esophagus, heart, kidneys, larynx, liver, lungs and mainstem bronchi, mandibular and mesenteric lymph nodes, nasal cavity and nasal turbinates. pancreas, parathyroids, pituitary gland, prostate or uterus/ovaries, salivary glands, skeletal muscle, skin with mammary gland, spleen, sternebrae or femur or vertebrae including marrow, stomach, thymus, thyroid gland, trachea, and urinary bladder.

Statistics:

yes: e.g data recording, survival analyses, calculation of incidence

Results and discussion

Results of examinations

Details on results:

No compound-related deaths occurred. The final mean body weight of rats exposed at 800 ppm was 23% lower than that of the controls for males and 16% lower for females. No compound-related clinical signs were observed. Liver weight to body weight ratios were similar in dosed and control rats . Inflammation of the nasal cavity was seen in all rats that received l,2-epoxybutane at 800 ppm but not at lower concentrations. The inflammation was present primarily in the dorsal and lateral portions of the nasal cavity and affected the respiratory and olfactory epithelium. The lesion was characterized by lymphocytic and neutrophilic infiltration of the mucosa and accumulation of purulent exudate in the lumen of the nasal cavity, with focal loss of epithelial cells from the mucosa.

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

200 ppm

Sex:

male/female

Basis for effect level:

other: overall effects

2

Dose descriptor:

LOAEC

Effect level:

400 ppm

Sex:

male/female

Basis for effect level:

other: overall effects

Target system / organ toxicity

Critical effects observed:

not specified