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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991-09-16 to 1991-10-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant (self-certified) proprietary study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Remarks:
self-certified including GLP compliance statement
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): trimellitic anhydride
- Physical state: White flake solid
- Lot/batch No.: ATTA 91-35 (TA 1281)
- Stability under test conditions: Stable when stored under recommended conditions
- Storage condition of test material: Room temperature (approximately 22°C)
- Other: The test article was prepared as a 50% (w/v) suspension in corn oil.

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 rats (Crl:CDR BR), approximately 6 weeks of age, purchased from Charles River Breeding Laboratories Inc. (Portage, MI). The rats weighed 130-227 g on arrival. They were acclimatised for at least 1 week and examined to ensure their health and suitability as test subjects. Rats selected for the study were identified by ear tags and cage cards. Purina Rodent Chow 5001 and reverse-osmosis purified water were provided ad libitum. The rats were housed in stainless steel cages suspended over deotized animal cage boards. The animal room average temperature and relative humidity were 22°C and 39%, respectively. Fluorescent lighting was provided on a 12 hour light/dark cycle.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test material was prepared as a 50% (w/v) suspension in corn oil. The flakes were first ground using a pestle and mortar, then the test article and corn oil was homogenised with a Polytron. The dosage formulation was stirred continuously whilst being administered at dosing volumes of 4, 7 and 10 mL/kg bw. Formulations were prepared fresh for each group and administered by oral gavage using a glass syringe equipped with a ball-tipped stainless steel needle.
Doses:
2000 mg/kg bw, 3500 mg/kg bw and 5000 mg/kg bw as a 50% (w/v) suspension in corn oil.
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
Animals were fasted for approximately 18 hours prior to dosing and for approximately 4 hours after dosing. Body weights were recorded prior to fasting and immediately prior to dosing, then at 7 and 14 days after dosing. Dosage calculations were based on fasted body weights. Rats were observed for clinical signs and mortality for 14 days after dosing. Necropsies were performed on all rats that died during the study, and those that survived to study termination.
Statistics:
The calculation method for the determination of the LD50 was based on Miller and Tainter (Proc. Soc. Exp. Bio. Med., 57:261-264, 1944)

Results and discussion

Preliminary study:
No preliminary results
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
3 340 mg/kg bw
Based on:
test mat.
95% CL:
1 740 - 6 410
Remarks on result:
other: Mortality incidences were 2 males in the 3500 mg/kg bw group and all animals in the 5000 mg/kg bw group.
Sex:
female
Dose descriptor:
LD50
Effect level:
2 030 mg/kg bw
Based on:
test mat.
95% CL:
700 - 5 890
Remarks on result:
other: Mortality incidences were 2 females in the 2000 mg/kg bw group, 5 females in the 3500 mg/kg bw group and all animals in the 5000 mg/kg bw group.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 730 mg/kg bw
Based on:
test mat.
95% CL:
1 730 - 4 290
Remarks on result:
other: Mortality incidences were 2 females in the 2000 mg/kg bw group, 2 males and 5 females in the 3500 mg/kg bw group and all animals in the 5000 mg/kg bw group.
Mortality:
The deaths were observed between 1 and 48 hours after administration.
Clinical signs:
Prominent clinical signs observed included hypoactivity, hypothermia, ataxia, salivation, discolouration around the mouth, wet/coloured inguinal fur, lacrimation, redness around the nose-eyes and discoloured paws. Rales, loss of righting reflex, pale appearance and diarrhoea were also observed, however not to the extent the other observations were seen. Surviving animals appeared essentially normal 3-4 days following test article administration. Salivation, redness around the nose/eyes, and discolouration of the paws and around the mouth were observed with higher incidences in the 2 g/kg dosage group due to the large number of survivors in this group.
Body weight:
An increase in mean body weight was observed in the animals which survived through the 14 day observation period.
Gross pathology:
Treatment related lesions observed at necropsy included thinning of the stomach walls in the 2000 mg/kg bw, stomach ulcerations in two, five and nine rats that died in the 2000 mg/kg bw, 3500 mg/kg bw and 5000 mg/kg bw, respectively, and discoloured areas in the stomach (indicative of haemorrhage and necrosis) seen in the majority of animals administered 3500 and 5000 mg/kg bw .
Distention of the gastrointestinal tract with gas and/or liquid was also present in several animals which died, however, these changes were considered autolytic in nature rather than treatment related.
Other findings:
No other findings reported.

Any other information on results incl. tables

Table 1: Summary of mortality data

Dose levels (mg/kg bw)

Number of deaths/group

 

Male

Female

Total

2000

0/5

2/5

2/10

3500

2/5

5/5

7/10

5000

5/5

5/5

10/10

LD50combined sexes

2730 mg/kg bw with a 95% confidence limits of 1730 - 4290

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of trimellitic anhydride (TMA) is estimated 3340 mg/kg bw in male rats, 2030 mg/kg bw in females and 2730 mg/kg bw in combined sexes. The LD50 is above 2000 mg/kg bw. On this basis, trimellitic acid does not warrant any classification according to Directive 67/548/EEC and Regulation (EC) No 1272/2008.
Executive summary:

Trimellitic anhydride was administered to three groups of 5 animals/sex at 2000 mg/kg bw, 3500 mg/kg bw and 5000 mg/kg bw. 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.

Mortality incidences were 2 females in the 2000 mg/kg bw, 2 males and 5 females in the 3500 mg/kg bw and all animals in the 5000 mg/kg bw. The clinical signs reported included hypoactivity, ataxia, hypothermia, lacrimation, salivation, redness around the nose, discoloration around the mouth, wet/discoloured inguinal fur and discoloured paws. Treatment related lesions observed at necropsy included thinning of the stomach walls in the 2000 mg/kg bw, stomach ulcerations in two, five and nine rats that died in the 2000 mg/kg bw, 3500 mg/kg bw and 5000 mg/kg bw, respectively, and discoloured areas as a sign of haemorrhage and necrosis was also reported in the stomach of several animals in the 3500 and 5000 mg/kg bw dose levels.

Under the conditions of this test, the oral LD50 of trimellitic anhydride for male was 3340 mg/kg with 95% confidence limits of 1740 - 6410 mg/kg bw. The oral LD50 of trimellitic anhydride for female was 2030 mg/kg with 95% confidence limits of 700 - 5890 mg/kg bw. The oral LD50 of trimellitic anhydride for combined sexes was 2730 mg/kg with 95% confidence limits of 1730 - 4290 mg/kg bw. On this basis, trimellitic anhydride does not warrant any classification according to Directive 67/548/EEC and Regulation (EC) No. 1272/2008.