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Toxicological information

Respiratory sensitisation

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Administrative data

Endpoint:
respiratory sensitisation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
IN-LIFE DATES: From: September 15, 1988 to October 13, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: There is no indication that the study was conducted according to GLP. For read-across justification see Section13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
This study does not follow any particular guidelines. The principle of this study was based on the exposure of rats to trimellitic acid (TMLA) as a particulate aerosol for 6 hours/day for 5 consecutive days. Following a three week rest period, the TMLA-exposed group and one control group were challenged with TMLA at the same concentration for 6 hours. The second filtered air-exposed group served as a non-challenged control. Two groups of 12 male rats each were exposed to 50 µg TMLA/m³, 6 hours/day for 5 days. Following a 3-week rest period, one group was challenge with a single inhalation exposure to 50 µg/m³ and the other group was not challenged.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Trimellitic acid (TMLA)
- Molecular formula (if other than submission substance): C9H6O6
- Molecular weight (if other than submission substance): 210.14
- Smiles notation (if other than submission substance): c1cc(c(cc1C(=O)O)C(=O)O)C(=O)O
- InChl (if other than submission substance): InChI=1S/C9H6O6/c10-7(11)4-1-2-5(8(12)13)6(3-4)9(14)15/h1-3H,(H,10,11)(H,12,13)(H,14,15)
- Structural formula attached as image file (if other than submission substance): see Illustration attachment

- Physical state: White to yellow crystalline powder
- Lot/batch No.: ID No. 10820-92)
- Stability under test conditions: Expected to be stable for the time of the study
- Storage condition of test material: Stored at room temperature
Trimellitic acid is the hydrolysis product of trimellitic anhydride

- Name of test material (as cited in study report): Trimellitic anhydride (TMA)
- Physical state: White flake
- Lot/batch No.: TA 128 F (ID No. 10820-23-D)
- Stability under test conditions: Expected to be stable for the time of the study
- Storage condition of test material: Stored at room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, MI, USA
- Age at study initiation: 6 weeks
- Weight at study initiation:
- Housing: Stainless steel cages
- Diet (e.g. ad libitum): Purina Rodent Chow ad libitum, except during the inhalation and approximately 18 hours prior to necropsy
- Water (e.g. ad libitum): Ad libitum, except during the inhalation exposures
- Acclimation period: two weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22C
- Humidity (%): 40%
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light


IN-LIFE DATES: From: September 15, 1988 To: October 13, 1988

Test system

Route of induction exposure:
inhalation
Route of challenge exposure:
inhalation
Vehicle:
unchanged (no vehicle)
Concentration:
Target concentration of 50 µg/m³

The analytical time-weighted average concentration of TMLA for the five exposures and challenge were 41.4 and 44.6 µg/m³, respectively. The time-weighted average challenge concentration of TMA was 42.0 µg/m³
No. of animals per dose:
3 groups of 10 rats/sex and 2 groups of 12 rats
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 5 to TMLA
- Exposure period: 6 hours/day
- Test groups: 3 groups/sex
- Control group: 2 groups exposed to filtered air control
- Duration: 5 days
- Concentrations: 50 µg/m³


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Exposure period: 6 hours
- Test groups: 3 groups/sex of which two groups exposed to TMLA and one group exposed to TMA
- Control group: 1 control group and 1 control group exposed to filtered air control
- Concentrations: 50 µg/m³
Challenge controls:
Yes, the challenge control was exposed to 50 µg/m³ of TMLA for 6 hours
Positive control substance(s):
none
Negative control substance(s):
none

Results and discussion

Results:
The analytical concentrations of TMLA ranged from 31.2 to 54.7 µg/m³ during the five exposures and from 42.5 to 46.8 µg/m³ during the challenge exposure. The average particles size was 1.6 microns with 98.1% of the particles being equal or less than 10 microns in size. During the TMA challenge exposure, TMA concentrations ranged from 41.3 to 43.1 µg/m³. TMA particle size averaged 2.33 microns with 99.5% of the particles being less than 10 microns.

No deaths occurred during the study.

A few male rats in each study group showed redness around the nose but it was deemed not to be treatment related. No significant clinical signs were noted in any rat during the study.

There were no statistically significant effects of treatment on body weight during the study.

At gross pathology, lung foci were reported in some rats in all groups including controls. There were no statistically significant differences between the TMLA-exposed and control rats, and between the challenged and non-challenged rats. There was a statistically significant effect of treatment on the combined male and female serum IgG antibody levels. The effect was considered to be artifactual since the non-challenged control rats had the highest serum IgG antibody levels. It was therefore concluded that there were no biological significance.

There were no statistically significant effects of treatment on either absolute or relative lung weights and volumes.
Positive control results:
Not applicable
Negative control results:
Filtered air control non-challenged and TMLA or TMA challenged were used during the course of the study. The negative control gained weight throughout the study. Clinical observations showed signs such as salivation, redness around the nose, alopecia and discoloured paws. There were no lesions reported at gross pathology. The animals gained weight during the course of the study. There were no effects seen on lung weights and volumes.

Any other information on results incl. tables

It was concluded that TMLA does not appear to induce respiratory sensitisation in the rat, nor does it have a cross-sensitisation reaction with TMA.

Applicant's summary and conclusion

Interpretation of results:
other: TMLA is not a respiratory sensitiser
Conclusions:
It is concluded that TMLA does not appear to induce respiratory sensitisation in the rat, nor does it have a cross-sensitisation reaction with TMA. Therefore, TMLA is not classified as a respiratory sensitiser according to Directive 67/548/EEC and Regulation (EC) No 1272/2008.
Executive summary:

This study was divided into two parts. The first part included three groups of 10 male and 10 female Sprague-Dawley rats each, one of which was exposed to trimellitic acid (TMLA) as a particulate aerosol at a target concentration of 50 ug/m3, 6 hours/day for 5 days. The remaining two groups were exposed to filtered air only. Following a 3 -week rest period, the TMLA-exposed group along with one filtered air-exposed group were challenged with the same concentration of TMLA for 6 hours. The second filtered air-exposed group served as a non-challenged control. In the second part of the study, two groups of 12 male rats each were exposed to 50 ug/m3 TMLA, 6 hours/day for 5 days. Following a 3-week rest period, one of the groups was challenged with a single inhalation exposure to 50 ug/m3 of trimellitic anhydride (TMA). The other group was not challenged.

The analytical time-weighted average concentrations of TMLA for the five exposures and challenge were 41.4 and 44.6 ug/m3, respectively. The time-weighted average challenge concentration of TMA was 42 ug/m3. The rats were observed for morbidity and mortality twice daily on weekdays and once daily on weekends and holidays during the study. Physical examinations were performed once prior to study initiation. Clinical observations were performed daily on weekdays during the exposure phase of the study and weekly thereafter. Body weights were measured at the initiation of the study, weekly during the study and at study completion prior to sacrifice. Blood samples were obtained from the femoral artery of each rat just prior to the scheduled necropsy. TMLA-specific serum IgG antibody levels were determined using Enzyme-Linked Immunosorbant Assay (ELISA). Gross necropsies were performed on all rats.

None of the rats died and no significant clinical signs were noted in any rat during the study. There were no statistically significant effects of treatment on body weight, absolute and relative lung weight and volume, lung foci or serum IgG antibody in either part of the study. Therefore, it can be concluded that TMLA (a degradation product of TMA in the presence of moisture) did not induce respiratory sensitisation in the rat, nor did it have a cross-sensitisation reaction with TMA.