Butyl 2,3-epoxypropyl ether

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

reproductive toxicity, other

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

To evaluate the inhalation repeated dose toxicity of the test substance male rats were exposed to 50 7-hour exposures to 4 different vapour concentrations.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Diablo Laboratories
- Weight at study initiation: 57 - 97 gram before acclimatization, at the start of experiment 90 -120 gram.
- Housing: Two to a cage
- Diet: Standard green feed from Simonsen Laboratories,
- Acclimation period: 2 weeks

Route of administration:

inhalation: vapour

Type of inhalation exposure (if applicable):

whole body

Vehicle:

air

Details on exposure:

The exposures were made in metal chambers, 200 litres in capacity, and the air flow ranged from 10 to 20 litres per minute, depending on the vapour concentration used. The constant metering device delivered the compound to the evaporator where it was vaporized in the air entering the chamber.

Details on mating procedure:

Not applicable

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The vapour concentrations were monitored at intervals ranging from twice daily to once weekly, by analysis of air drawn from the sampling port of each chamber. The vapour was absorbed from the air in pyridine, and reacted with pyridinium chloride; the amount of acid consumed was then measured.

Duration of treatment / exposure:

7 hours

Frequency of treatment:

daily except weekends

Dose / conc.:

38 ppm (nominal)

Dose / conc.:

75 ppm (nominal)

Dose / conc.:

150 ppm (nominal)

Dose / conc.:

300 ppm (nominal)

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Parental animals: Observations and examinations:

The animals were observed at intervals during exposure as well as before and after placement in the chamber, for signs of toxicity or aberrations from normal behaviour. They were weighed once weekly.

Postmortem examinations (parental animals):

At the end of the experimental period the survivors were decapitated under light ether anaesthesia for necropsy. After thorough gross inspection, the lungs, livers, and kidneys of all animals were freed of connective tissue blotted lightly to remove excess moisture and weighted for calculation of organ/bodyweight ratios. Sections of these tissues were preserved for microscopic examination. Sections were also preserved from alternate animals of brain, thyroid, thymus, heart, stomach, intestine, pancreas, adrenal, testis, seminal vesicles, and urinary bladder.
Microscopic examination was made of the tissues of 10 animals in each group, with the exceptions of those exposed to 300 ppm, only five of which survived 50 exposures. Tissues of one animal in this group that died after 40 exposures were included.

Statistics:

Organ/body weight ratios and percentage weight gains were statistically compared by the Student t-test.

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Animals in the 300 ppm group developed an emaciated appearance, and were ill-kempt in appearance, but showed no overt signs of toxicity. At 150 ppm, surviving animals were without further signs of toxicity except that weight gain was retarded.

Dermal irritation (if dermal study):

not examined

Mortality:

mortality observed, treatment-related

Description (incidence):

At 300 ppm, there were 5 deaths, all occurring between the twentieth and thirty-fifth exposures. At the level of 150 ppm, there was one death after 20 exposures. At 38 and 27 ppm, there were no deaths.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

A decrease in bodyweight gain was significant (p=0.05) in the 300 ppm group and in the 150 ppm groups. At lower doses there was no significance.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Atelectasis was the most common finding, appearing in the lungs of 4 controls and 18 of 35 experimental animals. Lung congestion was noted in 2 controls and 4 experimental animals. These lesions would not appear to be related to the treatment. There were no other findings among controls or animals exposed to 39 ppm.
One animal exposed to 75 ppm had severe pneumonia and slight patchy atrophy of the testis. Five animals exposed to 150 ppm had bronchopneumonia. Three of the five survivors in the 300 ppm group had pneumonia; two of these had atrophic testes, and one had also focal liver necrosis. Both the other animals had atrophic testes and atelectasis of the lungs, and one had focal liver necrosis.
The rat that died after 40 exposures had testicular atrophy, and pneumonia with a foreign-body reaction.

Histopathological findings: neoplastic:

no effects observed

Other effects:

not specified

Dose descriptor:

NOAEC

Effect level:

38 ppm (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

histopathology: non-neoplastic

Critical effects observed:

not specified

- Results for F1 and F2 generation: Not examined

- Examination on pups: Not applicable

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1957

Report date:

1957

Materials and methods

Principles of method if other than guideline:

To evaluate the inhalation repeated dose toxicity of the test substance male rats were exposed to 50 7-hour exposures to 4 different vapour concentrations.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butyl 2,3-epoxypropyl ether

EC Number:

219-376-4

EC Name:

Butyl 2,3-epoxypropyl ether

Cas Number:

2426-08-6

Molecular formula:

C7H14O2

IUPAC Name:

2-(butoxymethyl)oxirane

Test material form:

liquid

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Diablo Laboratories
- Weight at study initiation: 57 - 97 gram before acclimatization, at the start of experiment 90 -120 gram.
- Housing: Two to a cage
- Diet: Standard green feed from Simonsen Laboratories,
- Acclimation period: 2 weeks

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

The exposures were made in metal chambers, 200 litres in capacity, and the air flow ranged from 10 to 20 litres per minute, depending on the vapour concentration used. The constant metering device delivered the compound to the evaporator where it was vaporized in the air entering the chamber.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The vapour concentrations were monitored at intervals ranging from twice daily to once weekly, by analysis of air drawn from the sampling port of each chamber. The vapour was absorbed from the air in pyridine, and reacted with pyridinium chloride; the amount of acid consumed was then measured.

Duration of treatment / exposure:

7 hours

Frequency of treatment:

daily except weekends

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

38 ppm (nominal)

Doses / concentrations 2

Dose / conc.:

75 ppm (nominal)

Doses / concentrations 3

Dose / conc.:

150 ppm (nominal)

Doses / concentrations 4

Dose / conc.:

300 ppm (nominal)

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

The animals were observed at intervals during exposure as well as before and after placement in the chamber, for signs of toxicity or aberrations from normal behaviour. They were weighed once weekly.

Sacrifice and pathology:

At the end of the experimental period the survivors were decapitated under light ether anaesthesia for necropsy. After thorough gross inspection, the lungs, livers, and kidneys of all animals were freed of connective tissue blotted lightly to remove excess moisture and weighted for calculation of organ/bodyweight ratios. Sections of these tissues were preserved for microscopic examination. Sections were also preserved from alternate animals of brain, thyroid, thymus, heart, stomach, intestine, pancreas, adrenal, testis, seminal vesicles, and urinary bladder.
Microscopic examination was made of the tissues of 10 animals in each group, with the exceptions of those exposed to 300 ppm, only five of which survived 50 exposures. Tissues of one animal in this group that died after 40 exposures were included.

Statistics:

Organ/body weight rations and percentage weight gains were statistically compared by the Student t-test.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Animals in the 300 ppm group developed an emaciated appearance, and were ill-kempt in appearance, but showed no overt signs of toxicity. At 150 ppm, surviving animals were without further signs of toxicity except that weight gain was retarded.

Mortality:

mortality observed, treatment-related

Description (incidence):

At 300 ppm, there were 5 deaths, all occurring between the twentieth and thirty-fifth exposures. At the level of 150 ppm, there was one death after 20 exposures. At 38 and 27 ppm, there were no deaths.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

A decrease in bodyweight gain was significant (p=0.05) in the 300 ppm group and in the 150 ppm groups. At lower doses there was no significance.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

The only significant difference in organ/body weight ratios occurred in the kidneys and lungs of rats in the 300 ppm group, which were heavier than those of the control group (p=0.05). The record of the organ weights for the 75 ppm group was lost in a laboratory accident, but it may be assumed that there were no differences, since there were none at 150 ppm.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

There were few findings at necropsy, other than general decrease in body fat. One rat exposed to 150 ppm had tan discoloration of the thymus, and 2 others had small areas of atelectasis in the lung. One rat exposed to 300 ppm had a consolidated lobe in the lung; one had atelectasis of a lobe; another had very small testes; and another a brown discoloration of the thymus. No abnormalities were seen in the other exposure groups.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Atelectasis was the most common finding, appearing in the lungs of 4 controls and 18 of 35 experimental animals. Lung congestion was noted in 2 controls and 4 experimental animals. These lesions would not appear to be related to the treatment. There were no other findings among controls or animals exposed to 39 ppm.
One animal exposed to 75 ppm had severe pneumonia and slight patchy atrophy of the testis. Five animals exposed to 150 ppm had bronchopneumonia. Three of the five survivors in the 300 ppm group had pneumonia; two of these had atrophic testes, and one had also focal liver necrosis. Both the other animals had atrophic testes and atelectasis of the lungs, and one had focal liver necrosis.
The rat that died after 40 exposures had testicular atrophy, and pneumonia with a foreign-body reaction.

Histopathological findings: neoplastic:

no effects observed

Other effects:

not specified

Effect levels

Key result

Dose descriptor:

NOAEC

Effect level:

38 ppm (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

histopathology: non-neoplastic

Target system / organ toxicity

Critical effects observed:

not specified