Mixed LOF

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

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

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Studies provide observation-based human data which are inherently more reliable than animal data since they can deal with subtle effects are internally very consistent (dose and time dependent).

Data source

Reference

Reference Type:

publication

Title:

The threshold toxicology of gasoline vapor

Author:

Drinker P, Yaglou C, Warren M

Year:

1943

Bibliographic source:

Journal of Industrial Hygiene and Toxicology 25:225-232.

Materials and methods

Study type:

study with volunteers

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Multiple experiments are reported.
Experiment 1: 13 male subjects were exposed to whole commercial gasoline vapor at a concentration of approximately 1296 mg/m3 for 8 hours with 1 hour for lunch. At the end of the exposure period, subjects were examined and questioned.
Experiment 2: 8 female subjects were exposed to whole commercial gasoline vapor at a concentration of approximately 768 mg/m3 for 8 hours with 1 hour for lunch. At the end of the exposure period, subjects were examined and questioned.
Experiment 3: 8 female subjects (same as in experiment 2) were exposed to distillate from commercial gasoline at a concentration of approximately 721 mg/m3 for 8 hours with 1 hour for lunch. At the end of the exposure period, subjects were examined and questioned.
Experiment 4: 10 female subjects were exposed to distillate from commercial gasoline at a concentration of approximately 672 mg/m3 for 8 hours with 1 hour for lunch. At the end of the exposure period, subjects were asked to write down their impressions without leading questions to guide them.
Experiment 5: 9 male subjects were exposed to distillate from commercial gasoline at a concentration of approximately 2400 mg/m3 for 1 hour.
Experiment 6: 6 male subjects were exposed to distillate from commercial gasoline at a concentration of approximately 4320 mg/m3 for 1 hour.
Experiment 7: 5 male subjects and 1 female subject were exposed to distillate from commercial gasoline at a concentration of approximately 12480 mg/m3 for 1 hour.
Experiment 8: 4 male subjects were exposed to distillate from commercial gasoline at a concentration of approximately 51376 mg/m3 via a face-mask for 4 to 7 minutes.
Experiment 9: 3 male and 1 female subject were exposed to whole commercial gasoline vapor at a concentration of approximately 53725 mg/m3 via a face-mask for 5 to 5.5 minutes.

GLP compliance:

no

Remarks:

Pre-GLP era study

Test material

Test material information

Constituent 1

Reference substance name:

Gasoline

EC Number:

289-220-8

EC Name:

Gasoline

Cas Number:

86290-81-5

IUPAC Name:

Gasoline

Details on test material:

The description of the test material was not sufficient to more clearly establish the identity of the material. It is described as lead-free colorless, commercial gasoline purchased in 50 gallon drums obtained by open market purchase.

Two sample types were tested, a straight commercial gasoline and the volatile fraction obtained by heating straight commercial gasoline to less than 100 degrees centigrade.

Method

Type of population:

general

Subjects:

Exp. 1: 13 men, 23 to 45 years. 9 were employed as members of the laboratory staff. They were competent observers as a result of many experiments of similar type. They knew gasoline was being tested, and two of them had definite knowledge as to possible effects. Four had no connection with the laboratory.
Exp 2, 3: 8 women, ages 17 to 32. Four were laboratory employees and knew gasoline was being breathed but did not know what symptoms might occur. 4 had no connection with the laboratory.
Exp 4: 10 women, ages 17 to 22. None had any knowledge of the experiment of any sort. They knew they were to spend a day in an atmosphere containing a slight odor but had no knowledge as to the substance responsible.
Exp 5 through 9: All subjects were members of the laboratory staff. All were experienced observers and entirely impartial in reporting. Their ages varied between 23 and 45 years.

Ethical approval:

not specified

Remarks:

Study conducted in during a time period (1940s) when ethical approval requirements were uncommon.

Route of exposure:

inhalation

Reason of exposure:

intentional

Exposure assessment:

estimated

Details on exposure:

other: Exp 1-7, whole body. Exp 8-9, face mask.

Examinations:

In experiments 1-3, subjects were questioned as to their experience by means of typewritten sheets and by interviews. The typewritten questions suggested the possibility of eye irritation, etc.
In experiment 4, subjects were brought in from outside the testing laboratory. At the close of the day, they were asked to write down their impressions of the experience, without any leading questions to guide them. After preparing their statements, interviews were conducted.

The method in which results were reported for experiments 5-9 is not provided.

Results and discussion

Clinical signs:

Experiment 1: Slight hyperemia of the conjunctival vessels, 6; distinct hyperemia of the throat, 3.
Experiment 2: hyperemia of the conjunctival vessels, 2.
Experiment 3: No positive findings reported.
Experiment 4: One girl reported at the end of the day with very red eyes, a definite conjunctivitis. When questioned she said she had been under treatment for follicular conjunctivitis during the preceding two weeks but that she had noticed nothing particular during the day and had read and worked as she pleased. (The women were not examined in any way at the beginning of the test in order not to direct their attention to any particular parts of the body.)
Experiment 5: Positive findings included: cough or feeling in the throat as if catching cold, 2; irritation of the eyes, 4; headache, 2 (slight).
Experiment 6: Positive findings included: irritation of the nose and throat, 4; irritation of eyes, 5.
Experiment 7: Positive findings included: dizziness, 6; sickness at stomach, 1; cough or feeling as if catching a cold, 1; irritation or itching in the eyes, 5. The investigators reported mild intoxication when in the experimental room, coupled with a small amount of muscular incoordination.
Experiment 8: Nose and throat irritation noted within 2 minutes; dizziness and obvious unsteadiness began within 4 minutes. After 7 minutes, one volunteer stopped due to feeling decidedly drunk. He was able to walk straight but with a distinct effort. Two of the subjects were distinctly hilarious and very active. The acute effects wore off in a short time.
Experiment 9: Nose and throat irritation within 20 seconds to 1 minute. One subject coughed and sneezed steadily after the first 2 minutes. All became dizzy as in experiment 8. Voluntary termination occured in 5 to 5.5 minutes due to dizziness and a feeling of incoordination and drunkenness.

Any other information on results incl. tables

General summary of effects of gasoline vapors at low concentrations (experiments 1 -4)

All of the experiments showed that in groups of subjects there would always be a few who might have minor complaints when placed in concentrations of gasoline vapor detectable by smell. The complaints were slight; one or two individuals invariably noticed some gastrointestinal disturbance and the eye irritation was prominent. On further inquiry it was found that the substance causing eye irritation was distilled from gasoline at extremely low temperatures and in very small amounts.

  

General summary of high concentration experiments (exp 5 -9):

These studies have shown that gasoline vapor in 0.1 percent (approximately 4320 mg/m3) causes definitely unpleasant symptoms in a few subjects at the end of an hour. These symptoms are not those of exhilaration and drunkenness but are apt to be slight dizziness, nausea, and headache. When the gasoline concentration reaches 0.26 percent (approximately 12480 mg/m3), five subjects out of six remained under exposure voluntarily for 1 h, and the five subjects were all drunk and somewhat anesthetized. The sixth became nauseated at the end of 13 minutes and had to leave the room. When concentrations reach 1 percent (approximately 51376 mg/m3), both whole gasoline and distillate cause dizziness and drunkenness in about 5 minutes. The effect is abrupt and unescapable. The heavy concentration experiments re-emphasize the fact that the eye and throat irritating substance found in gasoline was lost in our light fraction.

Applicant's summary and conclusion

Conclusions:

Acute inhalation exposure to gasoline vapors produced central nervous system depression in human volunteers at the highest concentrations tested (4320 mg/m3 after 1 h exposure and 51376 mg/m3 after <10 min exposure).

Executive summary:

In a series of experiments focused on the evaluation of central nervous system effects, human subjects were exposed to vapors of whole commerical gasoline and gasoline distillate in increasing concentrations (672 mg/m3 to 53725 mg/m3) and exposure periods (<10 min to 8 h). The studies provide consistent results indicating that the degree of CNS effects increased with both exposure level and duration. Exposure to approximately 4320 mg/m3for an hour produced slight dizziness, nausea and headache. Exposure for an hour at 12480 mg/m3 produced a condition similar to drunkenness. At 53725 mg/m3, dizziness and drunkenness were apparent within 5 minutes.