Fuel gases, crude oil distillates

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline, animal experimental study. Limitations in design and/or reporting but otherwise adequate for assessment

Data source

Reference

Reference Type:

publication

Title:

The relative anaesthetic activity of the butanes and pentanes

Author:

Stoughton RW and Lamson PD

Year:

1936

Bibliographic source:

J. Pharmacol. Exp. Ther. Vol 58 pp 70-77

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The times taken for groups of mice to produce "light anaesthesia", "complete anaesthesia" and lethality were determined. The effects of isobutane on dogs was also examined.

GLP compliance:

no

Type of method:

in vivo

Endpoint addressed:

acute toxicity: inhalation

Test material

Test material information

Constituent 1

Reference substance name:

Isobutane

EC Number:

200-857-2

EC Name:

Isobutane

Cas Number:

75-28-5

IUPAC Name:

isobutane

Test animals

Species:

other: other: mouse and dog

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No details reported

Administration / exposure

Route of administration:

inhalation: gas

Vehicle:

other: other: mice - none. Dogs - oxygen

Details on exposure:

Mice: The time taken to produce "light anaesthesia" was determined by placing 2 mice in a 2L bottle filled with gas mixture at a known concentration and the bottle revolved mechanically at 14RPM. "Complete anaesthesia" was obtained by placing 5 mice in a 20 L bottle containing the gas mixture and a suspended bag of soda lime.
Dogs: Anaesthesia induced using a gas-oxygen machine, mask, soda-lime tube and gas bag. A Magill catheter with Guedel inflatable cuff was introduced and the dog connected with a spirometer containing the gas mixture. In order to avoid the high initial concentration necessary for cannula insertion, some dogs were anaesthetised by having their heads inside a specially designed gas chamber in which the concentration of gas could be controlled.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

2 hours (mice). No details reported for dogs.

Frequency of treatment:

Single exposure

Post exposure period:

48 hours.

Doses / concentrations

Remarks:

Doses / Concentrations:
6.7, 8.9, 11.3, 15.6, 17.9, 23.1 mM/L
Basis:

No. of animals per sex per dose:

Mice: 6 for 6.7, 8.9 and 11.3 mM/L, 10 for 15.6, 17.9 and 23.1 mM/L
Dogs: no details reported

Control animals:

other: positive controls - ether and cyclopropane

Details on study design:

The endpoint for ¿light anaesthesia¿ was taken as the degree of anaesthesia in which the mouse was unable to maintain an upright position, in a bottle revolving at 14 RPM. The endpoint for ¿complete anaesthesia¿ was the degree of anaesthesia in which the mouse was unable to regain an upright position after shaking the bottle. Lethality was recorded as the percentage of mice that died after 2 hours exposure to a given concentration.

Examinations

Positive control:

positive controls - ether and cyclopropane

Results and discussion

Details on results:

Mortality
No mortality following exposure to 6.7, 8.9, 11.3 or 15.6 mM/L. 60% and 100% mortality after 2 hours of exposure at 17.9 and 23.1 mM/L respectively. The average time to death was 72 and 28 mins for 17.9 and 23.1 mM/L respectively.

Clinical signs
Considerable excitement in mice during anaesthesia. On removal from the jar after 2 hours exposure, the mice recovered in 1-2 minutes. There were no abnormalities seen in the surviving mice 24-48 hours after cessation of exposure.

Dogs: Isobutane required a concentration of about 45% for anaesthesia and death occurred at concentrations of 55%.

Any other information on results incl. tables

Isobutane produced considerable excitement in mice during anaesthesia, but recovery of surviving mice after the 2 hour exposure was quick (1-2 mins). All surviving mice were normal for 24-48 hours after cessation of exposure.

 

In the dog, it was extremely difficult to produce good anaesthesia and relaxation with isobutane whereas control experiments with cyclopropane were carried out with ease.

 

Isobutane only gave good anaesthesia and relaxation at an almost lethal concentration (45% for anaesthesia , death at 55%).

 

Anaesthetic action of isobutane in mice:

(based on Stoughton RW and Lamson PD, 1936. J. Pharmacol. Exp. Ther. Vol 58 pp 70-77, Table 1)

concentration		No. Mice	Time to light anaesthesia (mins)	Time to full anaesthesia (mins)	% mortality 2 hours	Mean time to death (mins)	Mean recovery time
(mM/L)	volume (%)
6.7	15	6	60		0	-
8.9	20	6	17		0	-
11.3	23	6	26		0	-
15.6	35	10		25	0	-	3
17.9	41	10		3	60	72	4
23.1	52	10		2	100	28
The acute inhalation LC50(2 hour) in mice =>15.6 mM/L <17.9 mM/L. (>35% <41%) The acute inhalation LC50(2 hour) in mice = 410,000 ppm (974 mg/L)

Applicant's summary and conclusion

Conclusions:

Isobutane produced excitement in mice during anaesthesia, but recovery of surviving mice after the 2 hour exposure was rapid (1-2 mins). All surviving mice showed no clinical signs for the 24-48 hours observed after cessation of exposure. In the dog, good anaesthesia and relaxation with isobutane was difficult except at concentrations which were practically lethal (45% for anaesthesia , death at 55%).

Executive summary:

Isobutane produced excitement in mice during anaesthesia, but recovery of surviving mice after the 2 hour exposure was rapid (1-2 mins). All surviving mice showed no clinical signs for the 24-48 hours observed after cessation of exposure. In the dog, good anaesthesia and relaxation with isobutane was difficult except at concentrations which were practically lethal (45% for anaesthesia, death at 55%). Control experiments with cyclopropane were carried out with ease.

Isobutane only gave good anaesthesia and relaxation at an almost lethal concentration (45% for anaesthesia, death at 55%)