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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published proprietary study, conducted prior to development of the guidelines but broadly guideline-comparable.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Principles of method if other than guideline:
The study was broadly comparable to OECD 413, exposures were conducted for 4 hours/day, 5 days/week for a total of 58 exposures, and only two concentrations were tested.
GLP compliance:
no
Remarks:
older published literature study
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The material is made by Tennessee Eastman Company, catalogue No. 6580.

Test animals

Species:
rat
Strain:
Long-Evans
Sex:
male
Details on test animals and environmental conditions:
During exposure, the rats were individually caged and were placed in tiers in the chamber. The animals were housed individually between exposures and water and Purina Laboratory Chow were available ad lib.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Remarks on MMAD:
MMAD / GSD: The respirable fraction of the total number of aerodynamically sized particles (<5.0 µm) was 36%.
Details on inhalation exposure:
Dimethyl terephthalate was ground in a ball mill, screened through 80 mesh screening and compressed into a 40 cm³ dust tube under a pressure of 100 psi. The dust cloud of dimethyl terephthalate entered the chamber from the top via the air supply stream and was exhausted from the bottom. The airflow through the sampler was 2.0 litres/min

During exposure, the rats were individually caged and were placed in tiers in the chamber. The chambers were one cubic meter inhalation chambers (University of Rochester type). Each animal's position was alternated on succeeding days of exposure. The chambers were operated under negative pressure as a dynamic system with air supplied from the building air conditioning system (24±2 ⁰C, 50 ±5% RH).
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The concentration of dimethylterephthalate in the chamber was determined by collecting particles on a millipore filter housed in a standard millipore filter holder. The airflow through the sampler was 2.0 liters/min with samples collected form both levels and averaged. These samples were taken hourly during the first 11 four-hour exposure periods. The samples were extracted with chloroform and 1 microliter was quantitated against known dimethyl terephthalate standards on a Varian 2100 Aerograph gas chromatograph equipped with flame ionization detectors.
Duration of treatment / exposure:
4 hours per day, 5 days per week for a total of 58 exposures (exposures were not conducted on weekends or public holidays)
Frequency of treatment:
Exposures were conducted daily on 5 days per week.
Doses / concentrations
Remarks:
Doses / Concentrations:
86.4, 16.5 and 0 mg/m³ of dimethyl terephthalate.
Basis:
analytical conc.
No. of animals per sex per dose:
30 male rats/group
Control animals:
yes
Details on study design:
No further details on study design.
Positive control:
A positive control was not included.

Examinations

Observations and examinations performed and frequency:
All animals were weighed weekly. Haematological and blood chemistry determinations were performed on 15 rats randomly selected from each group, the following parameters were determined: haematocrit, haemoglobin, total and differential white cell counts, serum protein, serum glutamic oxaloacetic transaminase, serum alkaline phosphatase, blood urea nitrogen, blood glucose and ornithine carbamyl transferase..
Sacrifice and pathology:
Within 24 hours of the last exposure, ten rats were sacrificed. Tissue samples from all major organ systems were taken and the livers and kidneys were weighed. The remaining animals (20 per group) were observed for long-term effects.
Other examinations:
No other examinations reported.
Statistics:
No statistics reported.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY

There were no mortalities. The high concentration of DMT caused nose rubbing, preening and blinking soon after the start of exposure. These symptoms continued intermittently throughout the exposure period, and were repeated during successive exposures.

BODY WEIGHT AND WEIGHT GAIN
There were no effects on body weight gain, and no differences in terminal body weights in the sacrificed rats.

HAEMATOLOGY
There were no differences between DMT-exposed and control rats in any of the haematology parameters measures.

CLINICAL CHEMISTRY
There were no differences between DMT-exposed and control rats in any of the clinical chemistry parameters measures.

ORGAN WEIGHTS
There were no difference between DMT-exposed and control rats in absolute and relative kidney weights.

GROSS PATHOLOGY
No abnormalities detected.

HISTOPATHOLOGY: NON-NEOPLASTIC
No abnormalities detected.

Effect levels

Dose descriptor:
NOAEL
Effect level:
86.4 mg/m³ air (analytical)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Signs of irritation were noted during exposure to 86.4 mg/m³, no toxicological effects observed

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The average concentrations (over 58 exposures) of DMT in the high and low level exposure chambers were (mean±SD) 86.5±11.0 mg/m³ and 16.5±2.2 mg/m³, respectively. No DMT was detected in the control chamber.

Applicant's summary and conclusion

Conclusions:
Signs of irritation (nose rubbing, preening and blinking) were observed during exposure to the high level of DMT, therefore the NOAEL can be considered to be 86.4 mg/m³.
Executive summary:

Male Long-Evans hooded rats were exposed repeatedly to dimethyl terephthalate dust. Airborne particles of dimethyl terephthalate at concentrations of 16.5 and 86.4 mg/m³ for 4 hours/day, 5 days/week for a total of 58 exposures resulted in signs of irritation during the exposure at the high concentration. No other toxicologically adverse effects were observed. The respirable fraction of the total number of aerodynamically sized particles (<5.0 µm) was 36%. Based on this aerodynamic particle size value, the rats in the inhalation study received calculated average doses of 4.0 and 0.7 mg/kg bw. The NOAEL for this study can be considered to be 86.4 mg/m³.