Benzoic acid, 2,3,4,5-tetrachloro-6-cyano-, methyl ester, reaction products with 2-methyl-1,3-benzenediamine and sodium methoxide

Endpoint summary

Description of key information

Oral - Non-guideline study (equivalent or similar to OECD TG 401, pre-GLP) in rats: LD50 > 5000 mg/kg bw;

Inhalation - Non-guideline study (equivalent or similar to OECD TG 403, pre-GLP) with a structural analogue (CAS 106276-80-6) in rats: LC50 > 1.04 mg/L air (highest technically attainable concentration)

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:

1970

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP non-guideline study, available as unpublished report, predates implementation of GLP and/or development of study guidelines, restrictions in design and/or reporting but otherwise adequate for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

The test substance is administered orally by gavage at a dose level of 5000 mg/kg to rats of both sexes. Test substance was in suspension with arabic gum (1%)/ tap water. Application was followed by a 8 day observation period.

GLP compliance:

no

Remarks:

prior to GLP

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: CFE (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5- 6 weeks
- Weight at study initiation: average 135 g
- Housing: 5 animals per cage
- Diet: Nafag Nr. 185
- Maintenance: in air-conditioned room
- Fasting period before study: yes

Route of administration:

oral: gavage

Vehicle:

other: Arabic gum (1%)/ tap water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

Application concentration: 25%

DOSAGE PREPARATION (if unusual):
Fresh suspension with Arabic gum (1%)/ tap water

Doses:

5000 mg/kg

No. of animals per sex per dose:

5 animals/dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 8 days
- Frequency of weighing: at start and end of study period
- Symptoms recorded: yes

Statistics:

Interpolation on Probability (Schleicher and Schüll No. 298 ½)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No animals died.

Clinical signs:

other: Following symptoms were recorded: somnolence dyspnea exophthalmos ataxia yellow discolored feces

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (no data on purity), read across substance

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

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

Oral:

In an acute oral toxicity study (pre-GLP) similar to OECD Guideline 401, male and female CFE rats were administered 5000 mg/kg bw of the target substance (5 animals per dose group) by oral gavage. The test substance was suspended with Arabic gum (1%)/tap water. Application was followed by an 8-day observation period. Symptoms observed were somnolence, dyspnea, exophthalmos, ataxia and yellow discolored feces. No mortality was recorded. Therefore, the LD50 of the test substance is > 5000 mg/kg bw.

Inhalation:

Acute toxicity after inhalation of the test item was not evaluated. Reliable, experimental data of a structural analogue substance (CAS 106276-80-6) are available.

Acute inhalation toxicity of the analogue substance was examined in a reliable study (pre-GLP) similar to OECD Guideline 403, by a 4-h dust exposure (1000 mg/m³ air, nose only) to 9 male and female Tif:RAIf rats. The exposure was started 15 minutes after onset of the dust production, when the dust had reached an even dispersal throughout the chamber. The highest technically attainable concentration was tested. 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. The LC50 is considered to be greater than 1000 mg/m³.

On the basis of the similar chemical structure as well as properties, the results from this acute inhalation toxicity study can be transferred to the actual substance.

Justification for classification or non-classification

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 and inhalative toxicity under Regulation (EC) No. 1272/2008, as amended for the 13th time in Regulation (EU) 2018/1480.