5-chloro-2-(2,4-dichlorophenoxy)aniline

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted using the procedure described by Sachsse et al. (1973, 1976), which in principle was in accordance with the OECD TG 403. At the time the study was conducted, GLP was not mandatory. The test material was insufficiently characterized in the report, and no analytical purity was given. The test substance was dissolved into ethanol for aerosolization; this is not a representative exposure system for human hazard assessement because the substance is a solid, powdered substance. Exposures during manufacturing or formulation activity would be a dust, if any, and not to a fully respirable aerosol of test substance in ethanol. Thus, the study is considered as not reliable for hazard assessment and classification.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Sachsse et al. (1973, 1976)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-chloro-2-(2,4-dichlorophenoxy)aniline

EC Number:

260-480-4

EC Name:

5-chloro-2-(2,4-dichlorophenoxy)aniline

Cas Number:

56966-52-0

Molecular formula:

C12H8Cl3NO

IUPAC Name:

5-chloro-2-(2,4-dichlorophenoxy)aniline

Details on test material:

- Name of test material (as cited in study report): FAT 80023/G, 2-amino-4,2', 4'-trichlordiphenylether dest.
- Physical state: solid
- Analytical purity: no data
- Lot/batch No.: Partie 804
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:

rat

Strain:

other: Tif : RAIF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: young adults
- Weight at study initiation: 186 -231 g
- Fasting period before study: no data
- Housing: in groups of 10 in Macrolon cages type 4
- Diet: NAFAG, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 10 hours light per day

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: ethanol

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: nose-only exposure system according to the procedure of Sachsse et al. (Proceedings of the Europ. Soc. for the Study of Drug Toxicity, XV, 239-251, 1973; Chemische Rundschau, 29, No 38, 1976). For inhalation, the rats were placed in separate PVC-tubes positions radially around the plexiglass exposure chamber such that the snout and nostrils of the animals only were exposed to the aerosol.
- Exposure chamber volume: approximately 100 liter
- Method of holding animals in test chamber: separate PVC-tubes
- Method of conditioning air: The aerosol was generated by injecting a solution (50% w/w in ethanol) of the test substance with a Perfusor IV Syringe System (Bender and Hobein, 8051 Zurich, Switzerland) at a rate of 30, 45 and 60 mL/hr into an air stream.
- Source and rate of air: the air stream was discharged into the exposure chamber through a spray nozzle under a pressure of 2 atmospheres at a rate of 10 L/min.
- System of generating particulates/aerosols: spray nozzle (JATO, Luzern, Switzerland)
- Method of particle size determination: 4 stage Cascade Impactor
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: The chamber was maintained at a slightly negative pressure to prevent leakage of the test aerosol from the system.

TEST ATMOSPHERE
- Brief description of analytical method used: Particle size analysis was conducted twice during all exposures using a 4 stage Cascade Impactor (C.F. Casella and Co., Ltd., Regent House, Britannia Walk, London) with Selectron filters (Schleicher u. Schuell AG, Feldbach, Switzerland) of 25 mm diameter and a pore size of 0.2 µm at an air flow rate of 17.5 L/min.
The chamber concentration was determined 5 times (at approximately 1/2 hour and hourly thereafter) gravimetrically by sampling the test atmosphere through a Selectron filter of 50 mm diameter and a pore size of 0.2 µm.
In addition, environmental conditions within the inhalation chamber were monitored at approximately the same intervals as chamber concentration was measured: the temperature (with a Therm 2104 Contact Thermometer, Ahlborn Messung Regeltechnik, Holzkirchen/Germany), relative humidity
(with Vasala Humidity Indicator HMI 11, Kelag AG, Zurich/Switzerland) and oxygen content (with a Draeger E 15 Stationary Control System, Draegerwerk AG, Luebeck/Germany)
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): ethanol
- Concentration of test material in vehicle (if applicable): 50 %
- Justification of choice of vehicle: insoluble in water, solvent in ethanol/acetone

TEST ATMOSPHERE
- Particle size distribution: The particle size distribution analysis of the chamberairborne particles showed that at least 94 % were smaller than 7 µm in diameter for all exposures.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not given
- Exposure Atmospheres: The mean gravimetric concentrations: 1115 ± 50 mg/m³, 1744 ± 110 mg/m³, 2109 ± 229 mg/m³

VAPOUR SATURATION
- The vapour saturation treshold is calculated to be approx. 0.2758 mg/L (at 25°C).

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1115 ± 50 mg/m³, 1744 ± 110 mg/m³, 2109 ± 229 mg/m³

No. of animals per sex per dose:

10

Control animals:

other: control without treatment and control with the vehicle (ethanol)

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed during exposure at 1, 2 and 4 hours as well as at 2 hours post-exposure and daily for 14 days. Pharmacotoxic signs and mortality was recorded. Body weights were recorded immediately prior to exposure and at day 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: Gross pathologic evaluation was conducted at random on all animals dead within the 14 day observation period as well as the survivors killed at 14 days by asphyxiation with CO2. Particular attention was given to the respiratory tract.

Statistics:

The inhalation LC50 value including its 95 % confidence limits were determined at 14 days postexposure using the logit method (J. American Stat. As soc., 39: 357-65 (1944).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 1 967 mg/m³ air

Exp. duration:

4 h

Remarks on result:

other: 14 day post exposure observation

Mortality:

All rats that died, died during exposure.
ethanol control: one female died within 4 hours.
1115 mg/m³: no mortality;
1744 mg/m³: males: 2 animals died within 2 hours and 3 within 4 hours (mortality rate 50 %); females: 2 animals died within 2 hours and 1 within 4 hours (mortality rate 30 %);
2109 mg/m³: males: 2 animals died within 2 hours and 5 within 4 hours (mortality rate 70 %);; females: 1 animals died within 2 hours and 3 within 4 hours (mortality rate 40 %).

Clinical signs:

other: Exposure to all concentrations (1115, 1744 and 2109 mg/m³ test material) resulted in slight exophthalmus, cyanosis, ventral and curved body position as well as slight to moderate dyspnoea and ruffled fur. In one control, exposed to 50% w/w ethanol, at the

Body weight:

The body weight gain measured on day 7 is significantly reduced compared to the control group in males at the 1115 mg/m³ concentration (40.7 %) and in females and males at the 2109 mg/m³ concentration (males: 30.5 % / females 58.3 %) as well as in the ethanol control (males 32.0 % / females 33.3 %).

Gross pathology:

Gross necropsies were performed on all animals dead during the test and those killed at the end of the 14 day observation period.
No gross pathological changes were observed, except in ten (6 male and 4 female) rats exposed to 1744 and 2109 mg/m³ test material, mottled lungs as well as mottled and large livers were observed.

Other findings:

No further data

Applicant's summary and conclusion

Interpretation of results:

sligthly toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results the substance is considered to be slightly acute toxic via inhaltation.

Executive summary:

The LC50 of a 4 h aerosol induction is 1967 mg/m3, when evaluated for a 14 days post-treatment period.