Benzene-1,2,4-tricarboxylic acid 1,2-anhydride, oligomeric reaction products with ethane-1,2-diol and glycerol

Endpoint summary

Description of key information

The acute oral toxicity study showed mortality at doses > 4640 mg/kg bw. The LD50 is 6231 mg/kg bw.
The acute dermal toxicity study did not show  mortality up to 3170 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is pre-GLP and pre-OECD guidelines. The study has been performed according to a method similar to OECD 401

Principles of method if other than guideline:

Pre-guideline study. Three doses suspended in 2% CMC were applied by gavage to each 5 male and 5 female rats. Observation period was 14 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: raised in-house at Ciba-Geigy Ltd. Switzerland, Sisseln
- Weight at study initiation: 160 to 180 grams
- Fasting period before study: overnight
- Housing: Macrolon cages type 3, groups of 5
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): 55 +/- 5
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 14 hours dark, 10 hours light

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30%

Doses:

4640 mg/kg bw, 6000 mg/kg bw, 7750 mg/kg bw,

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: After 1 and 2 hours and daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology of organs

Statistics:

LD50 including 95% confidence limits were calculated with the logit model

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 6 231 mg/kg bw

Based on:

act. ingr.

95% CL:

>= 5 723 - <= 6 957

Mortality:

Animals started to die after 7 days at 6000 mg/kg bw
Animals started to die after 24 hours at 7750 mg/kg bw

Clinical signs:

sedation, dyspnoea, exophtahlmos, curved positiona and ruffled fur

Body weight:

no data

Gross pathology:

no substance-related deviations from normal morphology observed in organs

Dose Died within mg/kg bw 1 hour 24 hours 48 hours 7 days 14 days m f m f m f m f m f 4640 5 5 0 0 0 0 0 0 0 0 6000 5 5 0 0 0 0 2 1 2 1 7750 5 5 1 0 2 2 5 5 5 5

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 in the rat is about 6200 mg/kg bw and similar in both sexes.

Executive summary:

The LD50 oral in the rat is ca. 6200 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 231 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study is pre-GLP and pre-OECD guidelines. The study has been performed according to the method of Noakes, D.N. and Sanderson,, D. M: A method for determining the dermal toxicity of pesticides. Brit. J. Industr. Med. 26, pp 59-64 (1968). The result of the experiment is considered reliable.

Principles of method if other than guideline:

Pre-guideline study according to Noakes, D.N. and Sanderson,, D. M: A method for determining the dermal toxicity of pesticides. Brit. J. Industr. Med. 26, pp 59-64 (1968). Two doses suspended in 2% CMC were applied to the shaved backs of each 5 male and 5 female rats. Observation period was 14 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: raised in-house at Ciba-Geigy Ltd. Switzerland, Sisseln
- Weight at study initiation: 180 to 200 grams
- Fasting period before study: no
- Housing: Macrolon cages, individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): 55 +/- 5
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 14 hours dark / 10 hours light

Type of coverage:

occlusive

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2%

Details on dermal exposure:

TEST SITE
- Area of exposure: 60 cm2
- % coverage:
- Type of wrap if used: "dressing fixed with adhesive elastic bandage"

REMOVAL OF TEST SUBSTANCE
- Washing (if done): lukewarm water
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

2150 mg / kg and 3170 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: After 4 hours and daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology of organs

Statistics:

no

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 3 170 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no higher doses tested

Mortality:

none

Clinical signs:

Within 4 hours after treatment the rats in all dosage groups showed syspnoea, curved body position and ruffled fur. No local skin irritation was seen.
The animals recovered from systemic symptoms within 10-12 days.

Body weight:

no data

Gross pathology:

No substance-related gross organ changes were seen

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD0 is > 3170 mg/kg bw in the rat.

Executive summary:

The substance is practically non-toxic. The dermal LD0 is > 3170 mg/kg bw in the rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 170 mg/kg bw

Justification for classification or non-classification

The LD50 values in the oral and dermal toxicity studies are > 2000 mg/kg bw. Therefore no classification for acute toxicity is required.