Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, animal experimental study, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no further details reported

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Crl:CD(SD)BR
- Source: Charles River Laboratories, Margate, Kent UK
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 200-350g
- Housing: by sex, 5 per polypropylene cage with grid flooring
- Diet: SQC Rat & Mouse Maintenance Diet No. 1 ad libitum except during exposure
- Water: Mains water ad libitum except during exposure
- Acclimation period: minimum 3 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22±3°C
- Humidity: 40-70%
- Air changes: 15 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 13 January 1986 To: 12 March 1986

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
head only
Vehicle:
other: air
Details on inhalation exposure:
A heated ‘J’ tube with an in-line filter was used to produce the atmosphere within the cylindrical Perspex chamber of approximately 10 L internal volume. The p-xylene was metered to the generator using a flowmeter and heated by passage through a borosilicate glass tube located inside a furnace whose temperature was regulated with a variable resistor. The hot air then passed into the glass ‘J’ tube packed with glass beads. The p-xylene was slowly pumped into the ‘J’ tube where it vaporised and the resulting vapour cooled prior to passage through the in-line filter to remove any aerosol before passing into the chamber. Satisfactory control over the chamber atmospheres was achieved.
The exposure chamber temperature and humidity were 14-21°C and 30-54% respectively. The diluents air flow rate was 14-17 litres/minute. The oxygen concentration was 20-22%.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Twice hourly sampling through a Miran 1A infra-red gas analyser.
Duration of exposure:
4 h
Concentrations:
Nominal concentrations: 0, 3056, 4200, 5097, 5897, 7881 ppm
Measured concentrations: 0, 2502, 3754, 4349, 5003, 7553 ppm
7553 ppm is 75% of the lower explosive limit
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
The day of exposure was followed by a 14 day observation period.
Statistics:
Mean and standard deviation were calculated where appropriate. The median lethal concentration (LC50) and the 95% confidence limits were calculated using a probit analysis method.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
6 247 ppm
Exp. duration:
4 h
Remarks on result:
other: 27124 mg/m3
Sex:
male
Dose descriptor:
LC50
Effect level:
5 922 ppm
Exp. duration:
4 h
Remarks on result:
other: 25713 mg/m3
Sex:
female
Dose descriptor:
LC50
Effect level:
6 580 ppm
Exp. duration:
4 h
Remarks on result:
other: 28570 mg/m3
Mortality:
60% at 5003 and 7553 ppm mostly during exposure. No mortality at lower concentrations.
Clinical signs:
other: Body tremors suggestive of CNS involvement were seen at all concentrations during and after exposure, on the day of exposure. Mydriasis and respiratory difficulties including rapid respiration observed in majority of animals surviving 4349 ppm and higher.
Body weight:
No effect of p-xylene.
Gross pathology:
Animals that died showed signs of circulatory failure. There were no treatment-related changes in survivors at termination suggestive of irreversible or delayed target organ toxicity.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Groups of male and female rats were exposed (head only) to measured concentrations p-xylene vapour for 4 hours followed by a 14 day observation period. The LC50 was 6247 ppm (27124 mg/m3).
Executive summary:

Groups of male and female rats were exposed (head only) to measured concentrations p-xylene vapour for 4 hours followed by a 14 day observation period. The LC50 was 6247 ppm (27124 mg/m3). Clinical observations including body tremors suggestive of CNS involvement were seen at all concentrations during and after exposure, on the day of exposure.