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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:
supporting study
Study period:
1992-06-12 to 1992-06-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
GLP-compliant regulatory study
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
See attached justification document
Reason / purpose:
read-across source
Specific details on test material used for the study:
4-chloroformylphthalic anhydride
Preliminary study:
No preliminary results
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.55 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Nose-only exposure.
Mortality:
Three animals died during the course of the study. Mortalities were reported in one female and two males in the 2.33 mg/L bw dose group. At 2.33 mg/L there was 20% mortality in females and 40% mortality in males. Deaths occurred near the end of the exposure, approximately 1.5 hour and one day after exposure.
Clinical signs:
other: Animals showed signs of laboured breathing in four males, rales in five males and two females, redness around the nose/eyes in four males and two females, discoloration around the mouth in two males and one female, discoloration of the paws in three males
Body weight:
All surviving animals gained weight during the course of the study.
Gross pathology:
At necropsy, all the surviving rats displayed red foci on their lungs. Two males that died during the course of the study showed dark red coloured lungs. Other findings noted included fluid filled, enlarged or mottled appearance of the lungs.
Other findings:
No other findings reported.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The inhalation LD50 of trimellitic anhydride mono-chloride determined by applying the correcting factor based on the molecular weights is 2.55 mg/L i.e. 2550 mg/m^3 (the maximum achievable concentration). Based on the clinical and gross necropsy observations which suggest a severe pulmonary irritation, Trimellitic anhydride mono-chloride is classified Acute Toxicity Inhalation Category 4 according to the Regulation (EC) 1272/2008 (CLP) and the UN GHS Regulation.
Executive summary:

This acute inhalation toxicity study (limit test) was performed according to OECD Guideline 403 and in compliance with GLP. Sprague Dawley rats (5 animals/sex) were exposed by inhalation - nose only exposure to a single dose (2.33 mg/L) of the test substance (dust) for a single 4 h period. Clinical signs and body weights were recorded over a 14 day post exposure period. All animals that died during the course of the study and all surviving animals were necropsied.

Mortalities were reported in one female and two males. Clinical signs reported included laboured breathing, rales, redness around the nose/eyes, discoloration around the mouth and of thepaws, clear nasal discharge, wet inguinal fur and lacrimation. All surviving animals gained weight during the course of the study.At termination, all the surviving rats displayed red foci on their lungs. Two males that died during the course of the study showed dark red coloured lungs. Other findings noted included fluid filled, enlarged or mottled appearance lungs.

By analogy, under the test conditions, the inhalation LD50 of trimellitic anhydride mono-chloride determined by applying the correcting factor based on the molecular weights is 2.55 mg/L i.e. 2550 mg/m3 (the maximum achievable concentration). Based on the clinical and gross necropsy observations which suggest a severe pulmonary irritation, Trimellitic anhydride mono-chloride is classified Acute Toxicity Inhalation Category 4 according to the Regulation (EC) 1272/2008 (CLP) and the UN GHS Regulation.This study is considered as acceptable and satisfies the requirement for acute inhalation toxicity endpoint.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Remarks:
self-certified including GLP compliance statement
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: flakes
Details on test material:
- Name of test material (as cited in study report): Trimellitic anhydride
- Physical state: White flake solid
- Lot/batch No.: ATTA 92-09 (TA 1281)
- Stability under test conditions: Stable when stored under the recommended conditions
- Storage condition of test material: Stored in the original container at room temperature (22°C)
Specific details on test material used for the study:
Trimellitic anhydride

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
The animals were male and female Sprague-Dawley (Crl:CDR BR) rats, approximately 6 weeks of age, obtained from Charles River Laboratories Inc (Portage MI). The rats weighed 128-162 g two days after arrival. They were acclimatised for approximately 4 weeks, during which time they were examined to ensure their health and suitability as test subjects. Individuals were identified by ear tags and cage cards. The rats were acclimatised to the nose-only exposure tubes on three successive days during quarantine and prior to randomisation.
Purina Rodent Chow 5001 and reverse osmosis-purified water were available ad libitum. The rats were housed individually in suspended stainless steel cages with deotized animal cage boards underneath. The animal room average temperature and relative humidity were 23°C and 52%, respectively. Fluorescent lighting was provided on a 12 hour light/dark cycle.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The test material was ground in a ball mill for at least 2 hours using a 19 litre jar and stainless steel or porcelain balls. The material was placed in a sieve shaker and material passing through a No. 20 screen was collected and used for the exposure. The generation system consisted of an AccuRate dust feeding with a 0.5 inch helix. The ground test substance was delivered at a constant rate from the dust feeder through 3/4 inch stainless steel tubing into a transvector jet. The exposure was conducted in a 160 litre stainless steel nose-only chamber, airflow was maintained at 150 l/min during the exposure and the chamber was operated under slight negative pressure.
Upon determining output rates and particle sizes, a setting of 160 (approximately 7.2 g/min of output) gave the maximum obtainable chamber concentration while maintaining an acceptable particle size distribution; MMAD <5 µm with 90% or more ≤10 µm. Chamber temperature and airflow were monitored continuously and recorded every half-hour during the exposure. Particle size analysis was performed once using an Anderson 1ACFM Cascade Impactor.
Food and water were not available during the exposure period.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Concentration was measured gravimetrically by drawing a known volume of exposure atmosphere across a pre-weighed open-faced filter and dividing the sample weight gain by the volume of the sample. Four samples were collected during the exposure.
Duration of exposure:
4 h
Remarks on duration:
single exposure period
Concentrations:
The time weighted average aerosol concentration was 2.33 mg/L. This dose level was the maximum achievable concentration.
No. of animals per sex per dose:
One group with 5 females and 5 males.
Control animals:
no
Details on study design:
Rats were randomly selected for testing. Clinical signs were observed frequently after the exposure, then at least once per day for the remainder of the 14 day observation period. Body weights were recorded prior to exposure, one week later and immediately prior to necropsy. All animals that died during the course of the study and all surviving animals were necropsied.
Statistics:
Statistical analysis was not performed.

Results and discussion

Preliminary study:
No preliminary results
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.33 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Nose-only exposure. Two males and one female died at this exposure level
Mortality:
Three animals died during the course of the study. Mortalities were reported in one female and two males in the 2.33 mg/L bw dose group. At 2.33 mg/L there was 20% mortality in females and 40% mortality in males. Deaths occurred near the end of the exposure, approximately 1.5 hour and one day after exposure.
Clinical signs:
other: Animals showed signs of laboured breathing in four males, rales in five males and two females, redness around the nose/eyes in four males and two females, discoloration around the mouth in two males and one female, discoloration of the paws in three males
Body weight:
All surviving animals gained weight during the course of the study.
Gross pathology:
At necropsy, all the surviving rats displayed red foci on their lungs. Two males that died during the course of the study showed dark red coloured lungs. Other findings noted included fluid filled, enlarged or mottled appearance of the lungs.
Other findings:
No other findings reported.

Any other information on results incl. tables

Table 1: Summary of mortality data

Dose levels (mg/L)

Number of deaths/group

 

Male

Female

Total

2.33

1/5

2/5

3/10

LC50

>2.33 mg/L

The average exposure temperature was 24.2°C. Chamber relatively humidity could not be monitored.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute inhalation LC50 is estimated to be > 2.33 mg/L in both sexes. Based on the clinical and gross necropsy observations which suggest a severe pulmonary irritation, Trimellitic anhydride is classified Acute Toxicity Inhalation Category 4 according to the Regulation (EC) 1272/2008 (CLP) and the UN GHS Regulation.
Executive summary:

Trimellitic anhydride was administered to one group of 5 animals/sex at 2.33 mg/L. Clinical signs and body weights were recorded over a 14 day post exposure period. All animals that died during the course of the study and all surviving animals were necropsied.

Mortalities were reported in one female and two males. Clinical signs reported included laboured breathing, rales, redness around the nose/eyes, discoloration around the mouth and of the paws, clear nasal discharge, wet inguinal fur and lacrimation. All surviving animals gained weight during the course of the study. At termination, all the surviving rats displayed red foci on their lungs. Two males that died during the course of the study showed dark red coloured lungs. Other findings noted included fluid filled, enlarged or mottled appearance lungs.

Under the conditions of this test, the inhalation LC50 of trimellitic anhydride was greater than 2.33 mg/L, the maximum achievable concentration. However, the clinical and gross necropsy observations suggest that a single exposure to this concentration produced severe pulmonary irritation resulting in the death of 3/10 rats. Based on the clinical and gross necropsy observations which suggest a severe pulmonary irritation, Trimellitic anhydride is classified Acute Toxicity Inhalation Category 4 according to the Regulation (EC) 1272/2008 (CLP) and the UN GHS Regulation.