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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No information available: study reported in 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Proprietary non-GLP study, similar to OECD guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
: target exposure time of 4 hours was not achieved due to technical difficulties
Principles of method if other than guideline:
The methodology was similar to OECD 403 (limit test), the test concentration was 2 mg/l and the exposure period was 2 hours (the target concentration had been 5 mg/l and target exposure time 4 hours).
GLP compliance:
no
Remarks:
: study pre-dates mandatory GLP
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Purified terephthalic acid (identification no. 10820-3). The test substance was a white powder and was stored in the original container at room temperature (approx. 22°C). The purity was not stated, however the batch of terephthalic acid used in this study is considered to have been representative of commercial production and to have been at least 99% pure.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Male and female Sprague-Dawley rats weighing approximately 135 g on arrival. The rats were purchased from Charles River Breeding Laboratories, Inc. MI. All rats were acclimatised for approximately 1 week and examined carefully to ensure their health and suitability as test subjects. Individuals were identified by metal ear tags.Purina Rodent Chow 5001 (Ralston Purina Co.) and reverse-osmosis purified water were available ad libitum, except during the exposure period.During acclimatisation and the post-exposure observation periods, the rats were housed individually in suspended stainless steel cages with deotized animal cage boards beneath the cages (except during exposure). Air conditioned animal rooms were maintained at approximately 22°C and 40% relative humidity. Fluorescent lighting was provided on a 12 hour light/dark cycle. Rats were randomly selected for testing and assigned to a single group.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The rats were exposed for 2 hours to a particulate aerosol, generated from a single batch of the test article. The target concentration was 5 mg/L and the target exposure duration was 4 hours. The generator was a dry materials feeder. The test article was transported from a reservoir, by a rotating helix, to the generator outlet where it was blown by a Transvector Jet into the exposure chamber. The 68.2 litre chamber was made of glass, with a removable Plexiglass lid. The test article aerosol entered the chamber through a port near the top of one end of the chamber and exited through a pipe placed near the bottom of the chamber on the opposite side. The chamber exhaust was vented through a charcoal filter. A California-type fume hood enclosed the entire generation and exposure system. An attempt to determine the particle size, using a Mercer Cascade Impactor was made during the exposure. However, the quantity and nature of test article produced in the chamber contributed to a malfunction of the of the Mercer Cascade Impactor, therefore particle size could not be determined. The test article accumulated in the chamber during exposure such that the exposure was terminated after 2 hours.The average chamber temperature was 21°C, with a relative humidity of 40%.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The achieved concentration was measured gravimetrically by drawing a known volume of the test atmosphere across an open-face filter and dividing the weight of the test article collected by the sample volume.
Duration of exposure:
2 h
Remarks on duration:
Exposure was terminated prematurely due to technical difficulties
Concentrations:
The gravimetric time weighted average concentration was 2.02 mg/L, uncorrected for respirable particle size.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
Rats were observed during exposure, approximately 1-1/4 and 4 hours after exposure, and at least once per day for the remainder of the 14 day observation period. All rats were weighed prior to the exposure, weekly thereafter, and immediately prior to necropsy. All rats were sacrificed and necropsied at the end of the 14 day observation period.
Statistics:
Formal statistical analysis was not required.

Results and discussion

Preliminary study:
No preliminary results available.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.02 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
2 h
Remarks on result:
other: Time Weighted Average concentration
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.01 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Extrapolated from 2-hour exposure
Mortality:
There were no mortalities.
Clinical signs:
other: Diarrhoea, redness around the nose, wet/discoloured inguinal and abdominal fur and hairloss were observed during the study.
Body weight:
The mean initial body weights of the male and female rats were 198 g and 167 g, respectively. All rats gained weight progressively during the study.
Gross pathology:
All tissues examined in seven of the rats were within normal limits. Gross necropsy findings in the remaining three animals consisted of dark lungs in one male and enlarged mandibular lymph nodes in another male and female.
Other findings:
The test article accumulated on and around the rats during the exposure. All rats were covered with the test article when removed from the chamber, therefore each rat was rinsed with warm water following exposure.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, it was concluded that the LC50 in male and female rats was greater than 2.02 mg/L.
Executive summary:

Purified terephthalic acid was administered as a particulate aerosol by inhalation to a group of 5 male and 5 female Sprague-Dawley rats (whole-body exposure). The rats were exposed to an achieved concentration of 2.02 mg/L for 2 hours; exposure was terminated prematurely due to an accumulation of the test material in the exposure equipment. No deaths occurred. Signs of toxicity (diarrhoea, redness around the nose, wet/discoloured inguinal and abdominal fur and hairloss) were observed during the study. Weight gain was unaffected by treatment. Gross necropsy revealed dark lungs in three rats. The acute (2 -hour) inhalation LC50 of terephthalic acid was found to be >2.02 mg/L. By extrapolation, the 4 -hour LC50 is estimated to be >1.01 mg/L.