4-chloroformylphthalic anhydride

Acute Toxicity: oral

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

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

Test material information

Constituent 1

Reference substance name:

1,3-dioxo-1,3-dihydro-2-benzofuran-5-carbonyl chloride

IUPAC Name:

1,3-dioxo-1,3-dihydro-2-benzofuran-5-carbonyl chloride

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 or test system 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:

other: 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 lo

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.