Benzoic acid, 2,3,4,5-tetrachloro-6-cyano-, methyl ester, reaction products with 4-[2-(4-aminophenyl)diazenyl]-3-methylbenzenamine and methanol sodium salt (1:1)

Endpoint summary

Description of key information

Oral or inhalative administration of the test material / analogue did not cause mortalities, organ changes or clinical signs of toxicity. Therefore, LD50 oral is considered to be greater than 6000 mg/kg bw and LC50 greater than 1000 mg/m3.

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:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

In an acute oral toxicity study the test substance was administered to Tif: RAIf rats (5/sex/dose) by oral gavage (3170, 4640 and 6000 mg/kg), followed by a 14 day observation period. The test substance was suspended with polyethylene glycol (PEG400). Physical condition and rate of deaths were monitored throughout the whole observation period. At the end of the observation period animals were submitted at random to a necropsy.

GLP compliance:

not specified

Remarks:

prior to GLP implementation

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 on the premises
- Weight at study initiation: 160 - 180 g
- Fasting period before study: Animals fasted overnight
- Housing: During the treatment and observation period the animals were housed in groups of 5 in Macrolon cages (type 3)
- Diet: rat food, NAFAG, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: a minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 10 hours light cycle day

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on oral exposure:

DOSAGE PREPARATION:
The test substance was suspended with polyethylene glycol (PEG 400) Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

Concentration (%) of formulation: 30 %

Doses:

3170, 4640 and 6000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Physical condition and rate of deaths were monitored throughout the whole observation period.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 6 000 mg/kg bw

Mortality:

No mortality was observed.

Clinical signs:

other: Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, curved position and ruffled fur. The animals recovered within 8 to 12 days.

Gross pathology:

No substance related gross organ changes were seen.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 in rats of both sexes observed over a period of 14 days is greater than 6000mg/kg. The test material has therefore practically no acute toxicity to the rat by this route of administration.

Executive summary:

A study similar to OECD Guideline 401 was performed. The acute oral LD50 in rats of both sexes observed over a period of 14 days is greater than 6000mg/kg. The test material has therefore practically no acute toxicity to the rat by this route of administration.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

6 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

no data on purity

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Principles of method if other than guideline:

K. Sachsse, L. Ullmann, G. Voss and R. Hess: Measurement of inhalation toxicity of aerosols in small laboratory animals. In: Proceedings of the Europ. Soc. for the Study of Drug Toxicity. Vol. XV, pp. 239-251, Zurich, June 1973

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif:RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 185-190 g
- Housing: 9 per cage (Macrolon, Type 4)
- Diet (e.g. ad libitum): NAFAG, Gossau SG, CH; ad lib.
- Water (e.g. ad libitum): unspecified; ad lib.
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-1
- Humidity (%): 55+-5
- Photoperiod (hrs dark / hrs light): 10 / 14

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

The dust was generated by injecting the test material with the help of a "Grafix Exaktomat Injector" into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm. at a rate of 20 L/min. The concentration and the particle size distribution of the dust in the vicinity of the animals were monitored at 1 hour intervals throughout the dust exposure. The concentration was determined gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 L/min. The size distribution of the dust particles was measured with a Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0-2 µm (Schleicher and Schuell) at an air flow rate of 17.5 L/min.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1.04 +- 0.07 mg/L ( original data: 1041 +- 69 mg/m3)

No. of animals per sex per dose:

9

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation intervals were not reported; weighing was not performed
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1.04 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No mortality and signs of toxicity observed

Mortality:

No mortality observed

Clinical signs:

other: No signs of toxicity observed

Body weight:

not measured

Gross pathology:

No substance related gross organ changes were seen.

Interpretation of results:

GHS criteria not met

Conclusions:

The LC50 of a 4 hour dust exposure for rats of both sexes is greater than 1000mg/m3 air, when evaluated for a 14 day posttreatment observation period.

Executive summary:

A study similar to OECD Testguideline 403 was performed. The LC50 of a 4 hour dust exposure for rats of both sexes is greater than 1000mg/m3 air, when evaluated for a 14 day posttreatment observation period.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

1 000 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study the test substance was administered to Tif: RAIf rats (5/sex/dose) by oral gavage (3170, 4640 and 6000 mg/kg), followed by a 14 day observation period. The test substance was suspended with polyethylene glycol (PEG 400). Physical condition and rate of deaths were monitored throughout the whole observation period. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, curved position and ruffled fur. The animals recovered within 8 to 12 days. They were submitted at random to a necropsy at the end of the observation period. No substance related gross organ changes were seen. The acute oral LD50 of the test substance in rats of both sexes observed over a period of 14 days is greater than 6000 mg/kg.

Read across justification

Acute toxicity after inhalation of the test item was not evaluated; reliable, experimental data of an analogue are available. The substances share high similaritiy in structure and have comparable physico-chemical properties. All substances are solids of poor water solubility and insoluble in most of the common organic solvents. The molecular weight of the compounds is higher than 600 g/mol. The molecules includes phthalimid-like structures and bear the potential to release chlorinated phthalimid after enzymatic or bacterial cleavage. Therefore, these analogues substance were choosen to examine acute dermal toxicity and acute inhalation toxicity.

Procedure and observations

Acute inhalation toxicity was examined by a 4h dust exposure (~ 1000 mg/m3) to 9 male and female rats. The exposure was started 15 minutes after onset of the dust production, when the dust had reached an even dispersal throughout the chamber. After a 4 hour inhalation the rats were returned to their cages. Physical condition and incidence of death were monitored throughout an observation period of 14 days. None of the animals died, organ changes or clinical signs of toxicity were not observed.

Results and discussion

Oral or inhalative administration of the test material / analogue did not cause mortalities, organ changes or clinical signs of toxicity. Therefore, LD50 oral is considered to be greater than 6000 mg/kg bw and LC50 greater than 1000 mg/m3.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral toxicity under Regulation (EC) No. 1272/2008.