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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP status not known, non-guideline study, published in peer reviewed literature, limitations in design and/or reporting but otherwise adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
Petroleum hydrocarbon toxicity studies: V. Animal and human response to vapors of mixed xylenes.
Author:
Carpenter CP, Kinkead ER, Geary DJ, et al.
Year:
1975
Bibliographic source:
Toxicol Appl Pharmacol 33:543-558.

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
Mixed xylenes (m- 65.01%, o- 7.63%, p- 7.84% and ethylbenzene 19.27%).

Test animals

Species:
dog
Strain:
Beagle
Sex:
male
Details on test animals and environmental conditions:
No details reported

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
no details
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Gas chromatography.
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
6 hours/day, 5 days/week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 180, 460 or 810 ppm
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
0, 0.77, 2.0 or 3.5 mg/L
Basis:
analytical conc.
No. of animals per sex per dose:
4 males
Control animals:
yes
Details on study design:
Groups of 4 male beagle dogs were assigned randomly to each of three graded levels of mixed xylenes or to the solvent- free air-control. They were exposed for 6h/day, 5 days/week for 13 weeks (65 days of exposure) and then terminated. .

Positive control:
No

Examinations

Observations and examinations performed and frequency:
Measurements included body weight change, food consumption was followed 1 day of each week, initial and terminal electrocardiograms were made, and urine analyses were performed. Evaluations on blood included: haematocrit, total erythrocyte count, reticulocyte count, total and differential leucocyte counts, serum alkaline phosphatase (SAP), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxalacetic transaminase (SGOT) and blood urea nitrogen (BUN), bilirubin and blood glucose.
Sacrifice and pathology:
Liver and kidney weights were recorded at termination. The following tissues were taken for microscopic examination: adrenal, brain, pituitary, trachea, thyroid, parathyroid, lung, heart, liver, kidney, spleen, stomach, duodenum, pancreas, ileum, jejunum, colon, skeletal muscle, sciatic nerve, and bone marrow section. Bifurcation of the trachea, pharynx, tonsil, nasal mucosa were also taken. All tissues were examined at each time point for the high dose and control groups, but for the low and intermediate dose only lung, liver, kidney, heart, spleen, adrenal, thyroid, parathyroid, trachea, oesophagus, and bone marrow section were examined.
Statistics:
No details

Results and discussion

Results of examinations

Details on results:
There were no treatment-related differences for any of the endpoints evaluated.

Effect levels

Dose descriptor:
NOAEC
Effect level:
>= 810 ppm
Sex:
male
Basis for effect level:
other: 3515 mg/m3

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The NOAEC of mixed xylenes for male dogs exposed 6h/day for 5 days in each of 13 weeks was >=3515 mg/m3.
Executive summary:

Male dogs were exposed 6h/day for 5 days in each of 13 weeks to 0, 0.77, 2.0 or 3.5 mg/L (0, 180, 460 or 810 ppm) mixed xylenes. The NOAEC was >=3515 mg/m3.