Acetylene

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

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

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline animal experimental study, predates implementation of GLP and/or development of study guidelines. Deficiencies in study design and reporting mean that it is not acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1957

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

20 rats were exposed to a concentration of methylacetylene sufficient to cause anaesthesia for 6 hours/day, 5 days/week for 6 months

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

methylacetylene

IUPAC Name:

methylacetylene

Constituent 2

Reference substance name:

Propyne

EC Number:

200-828-4

EC Name:

Propyne

Cas Number:

74-99-7

IUPAC Name:

prop-1-yne

Details on test material:

- Source: Methylacetylene was purchased from Air Reduction Chemical Company, New York, USA
- No further details

Test animals

Species:

rat

Strain:

other: albino

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight: average initial weight 280 g
- An equal number of animals were housed in the same laboratory to serve as controls (average initial weight 260 g)

ENVIRONMENTAL CONDITIONS
- The Laboratory temperature was controlled to 25±1°C
- No further details

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 500 L stainless steel chamber
- Methylacetylene vapour was mixed with room air and injected into the chamber via an inlet device
- A constant flow rate was maintained during exposure using a pressure reducing valve and an orifice flowmeter, which was connected to a water manometer and allowed constant monitoring of the flow of methylacetylene gas

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Atmospheric concentrations of methylacetylene were determined chemically using the analytical method of Hanna & Siggia (1949). Following equilibration of the chamber, samples were drawn through a series of 6 bubbles, connected in tandem and containing methanol. The quantity of chamber atmosphere drawn through the bubbles was measured using a "Precision" wet test meter. The contents of each bubbler were analysed separately and added to give the total concentration of methylacetylene present. Blank samples were run from other studies using chambers without methylacetylene to determine the contribution of animal metabolites and this 2000 ppm blank result was then subtracted from the total amount of methylacetylene analysed to give a true concentration.

Duration of treatment / exposure:

6 hours/day

Frequency of treatment:

5 days/week for 6 months

Doses / concentrations

Remarks:

Doses / Concentrations:
28,700 ppm
Basis:
other: average by calculation

No. of animals per sex per dose:

20 male rats

Control animals:

yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least daily for mortality

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: detailed clinical observations were recorded during and after each exposure

BODY WEIGHT: Yes
- Time schedule for examinations: at approximately weekly intervals and at termination

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
- At the end of the study, all animals were killed and examined macroscopically

HISTOPATHOLOGY: Yes
- Lung, liver, kidney, heart, spleen and gastrointestinal tract were examined microscopically

Statistics:

Non specified

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not specified

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

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
- Slight ataxia was noted within 7 minutes of the first exposure. After 30 minutes most rats were lying on the chamber floor in early anaesthesia.
- Pecking of the head was noted throughout the first exposure. During remaining exposures rats were observed to be in one position lying either on the abdomen or on the side with gross tremors of the head and extremities. The rats appeared unable to maintain balance.
- All animals recovered rapidly after exposures were terminated.
- Animals were depressed after exposure and their fur was wet, discoloured and ruffled. Rats were 'unthrifty' after about 2 months on study.
- Eight (40%) rats died. Times of death were listed as 21, 34 (2 deaths), 46, 74, 95, 102 and 103 days. Two of the controls died.

BODY WEIGHT AND WEIGHT GAIN
- Over the course of the study, weight gain was slightly retarded in exposed rats

GROSS PATHOLOGY
- Gross pathology of rats that died was limited to the lungs, which appeared dark red. The lungs remained distended when the thorax was opened, but no oedema fluid was found. On palpitation the lungs had a firm consistency. A purulent empyema was observed in one rat.
- In exposed rats that survived to termination the lungs were also discoloured and remained distended. Discolouration ranged from speckled red areas to a homogeneous, dark red, haemorrhagic appearance.
- Cut sections of lungs were a homogeneous dark red colour and either oedema fluid or blood could be expressed from them.
- Lungs from 3 of the 12 surviving animals had cysts which contained a 'cheesy material'.
- The remaining organs appeared to be within normal limits.

HISTOPATHOLOGY: NON-NEOPLASTIC
- Microscopic pathology of the lungs showed definite pulmonary irritation.

Effect levels

Dose descriptor:

LOAEC

Effect level:

28 700 ppm

Sex:

male

Basis for effect level:

other: see 'Remark'

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Methylacetylene is of low repeated dose toxicity to rats and the site of toxicity is limited to the lungs, even at extremely high exposure concentrations (28,700 ppm, equivalent to 47026 mg/m3).

Executive summary:

A group of 20 male rats were exposed to 28,700 ppm methyl acetylene for 6 hrs/days, 5 days/week for 6 months. There was 40% mortality during the exposure period. Clinical signs during the first 2 months exposure included ataxia, unsteadiness/ unable to balance and gross tremors but these reduced in severity as exposure continued. Animals showed reduced body weight gain over the first 2 months. At necropsy following 6 months exposure, there was microscopic evidence of pulmonary irritation.

28,700 ppm, equivalent to 47026 mg/m³ is considered a LOAEC in this study.