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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:
From January, 31 1996 to March, 21 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Well described study performed according to a standardised method with acceptable deviations. Acceptablme for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Only males were tested. No necropsies were performed.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report): Trimellitic anhydride mono-chloride (product name: TAC)
- Physical state: Light yellow solid
- Storage condition of test material: Cool place preservation
-Supplier: Nippon Fine Chemical
Specific details on test material used for the study:
4-chloroformylphthalic anhydride

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan SLC, Inc
- Age at study initiation: 5-week old
- Weight at study initiation: 130.4 - 166.3g
- Fasting period before study: at least for 16 hours on the day before treatment
- Diet (e.g. ad libitum): cubed diet (the Funabashi farm, F-2)
- Water (e.g. ad libitum): tap water from town water
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25
- Humidity (%): 45-65
- Air changes (per hr): 15 to 25 air change rates/hour
- Photoperiod (hrs dark / hrs light): lighting 12 hours/day (7:00 to 19:00)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25% w/v

DOSE VOLUME APPLIED: 5.4 - 20.0 ml/kg
Doses:
1347, 1751, 2276, 2959, 3846, and 5000mg/kg (common ratio 1.3)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily (each morning). During the first day after exposure, observations were made immediately after ingestion and then at 30 min, 1 hour, 2 hours and 4 hours after ingestion.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Results and discussion

Effect levels
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
3 192 mg/kg bw
Based on:
test mat.
95% CL:
2 744 - 3 773
Mortality:
100% mortality at the highest tested dose of 5000 mg/kg during the first day after ingestion.
0% mortality observed at 2276 mg/kg.
All dead were observed during the first 3 days after ingestion.
Clinical signs:
At 1347 mg/kg during the first day of exposure salivation was observed on 5 animals , lacrimation was observed on 2 animals and loose stool was observed on 5 animals.
At 1751 mg/kg, main clinical effects are diarrhea which was observed on 2 animals and loose stool which was observed on 3 animals on the first day.
At 2276 mg/kg, diarrhea was observed on all animals on the first day and all animals showed a decrease in locomotor movement.
At 2959 mg/kg, one animal was found dead after 2 days and another one dead after 3 days. Other animals showed a decrease in locomotor movement and diarrhea at 2 days.
At 3846 mg/kg after 2 days, 2 rats died at day 1 and 2 other died at 2 days. Other animals showed a decrease in locomotor movement, diarrhea and loose stool.
At 5000 mg/kg all animals died the first day after ingestion.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of Trimetillic anhydride mono-chloride is estimated 3192 mg/kg bw in male rats. The LD50 is above 2000 mg/kg bw.
Executive summary:

In an acute oral toxicity study, performed according to a standard method equivalent to the OECD 401 Guideline, the substance 4 -chloroformylphthalic anhydride (TMAC) was administered by oral gavage, to male Sprague-Dawley rats at the doses of 1347, 1751, 2276, 2959, 3846, and 5000 mg/kg (5 animals/dose level). The test substance was diluted in olive oil. Clinical signs were checked for a period of up to 14 days.

Oral LD50in male rats = 3192 mg/kg bw

Clinical effects were observed at all tested doses. Animals died at concentrations from 2959 mg/kg to 5000 mg/kg.

Clinical effects observed were salivation, lacrimation, diarrhea or loose stool, hematuria, decrease in locomotor movement and decrease in respiration. All survival animals recovered from clinical signs after 5 days.

 

Based on the results of this study, 4 -chloroformylphthalic anhydride is not classified for acute oral toxicity according to the Regulation (EC) 1272/2008 (CLP) but is classified Acute Toxicity Oral Category 5 according to the UN GHS Regulation. This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.