Thionyl dichloride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline Study with acceptable restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Humidity of test atmosphere during exposure had to be reduced as the test substance hydrolyses in contact with humidity.

Principles of method if other than guideline:

Five male and five female Wistar rats were exposed to 5, 63, 403, 1326, 1596, 2544, 2832, 7986, 9318 mg thionyl chloride/m³ (vapour) for 4 hours. The animals were observed for mortality, weight and clinical signs through day 14. Exploratory lung function tests were conducted and a gross necropsy was performed.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

7719-09-6

IUPAC Name:

7719-09-6

Constituent 2

Reference substance name:

Thionyl dichloride

EC Number:

231-748-8

EC Name:

Thionyl dichloride

Cas Number:

7719-09-7

Molecular formula:

Cl2OS

IUPAC Name:

thionyl dichloride

Details on test material:

- Name of test material (as cited in study report): Thionylchlorid
- Physical state: vapour
- Analytical purity: 99.8 %
- Purity test date: 27 June 1985
- Lot/batch No.: sample from 25 June 1985
- Stability under test conditions: a sufficient amount of test material was stable enough for exposure; actual concentrations in breathing zone were verified by analytical determination

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen: Wistar Bor: WISW (SPF-Cpb)
- Age at study initiation: approx. 10 wks
- Weight at study initiation: 180 - 220 g mean weight
- Fasting period before study: not applicable, inhalation
- Housing: 5/cage
- Diet (e.g. ad libitum): Altromin 1324 - maintenance diet for rats and mice, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 1 wk


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 40 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose/head only

Vehicle:

other: air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel inhalation chamber (dimensions: diameter = 30 cm, height = 28 cm) to which animal exposure tubes are attached, preventing contamination of the fur. Design of chamber prevents mixing of original test atmosphere with the exhalation air of the animals, which prevents the formation of hydrolysates caused by the humidity in the exhaled air.
- Exposure chamber volume: approx. 10 liter according to the authors (approx. 19.8 liters according to a calculation based on the reported dimensions of the chamber).
- Method of holding animals in test chamber: fixation of head and nose to the breathing zone by limitation of back off space in the exposure tubes.
- Source and rate of air: pressurized, filtered and dried air, 10.1 to 18.1 l/min, depending on required dilution in the respective dose groups
- Method of conditioning air: Pressurised air was generated by two compressors working in parallel, the generated air was dried and automatically conditioned by removing dust and oil, working pressure of 8 to 10 bar was reduced by reduction valves. The primary and dilution air used for the preparation of the test atmosphere were additionally dried. Ratio between supply and exhaust air was adjusted to ensure removal of 60 to 80 % of the supplied test atmosphere and a constant airflow towards the animals. These conditions ensured a constant air exchange, under comparable conditions a steady state is formed within 3 minutes (McFarland, 1976).
- System of generating vapours: 5 ml thionyl dichloride were filled into a small impinger tube kept at a temperature of 20°C by thermostatical control. Specified volmina of the gas atmosphere on top of the fluid were withdrawn by gas piston pumps via gas tight tubing (primary air), mixed with dilution air and directed into the inhalation chamber.
- Method of particle size determination: not applicable
- Treatment of exhaust air: remaining thionyl dichloride in the exhaust air was removed by reaction with NaOH in wash bottles.
- Temperature, humidity, pressure in air chamber: temperature and humidity were measured at the beginning, during and shortly before the end of exposure and a mean value calculated, air flow was constantly monitored throughout exposure. Temperature in the chamber ranged from 21 to 24°C, and relative humidity in the chamber exhaust air ranged from 17 to 44 % in the various exposure groups.


TEST ATMOSPHERE
- Brief description of analytical method used: nominal concentration was calculated from the weight difference of the impinger before and after the test, and the flow through of the inhalation chamber.
For analytical determination of the concentration the test substance was directed through an aqueous solution of sodium tetrachloromercurate. The resulting sulfur dioxide forms a dichlorosulfitemercurate complex which reacts with hydrogenchloride-discoloured pararosaniline and formaldehyde to a red-violet sulfonic acid. Determination of the concentration was performed by spectrophotometry at 560 nm (Eben, 1986).
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not applicable, vapour
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not applicable, vapour

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Methodology of analytical determination was reported separately (Eben, 1986); samples were taken from the breathing zone of the animals

Duration of exposure:

4 h

Concentrations:

analytical: 5, 63, 403, 1326, 1596, 2544, 2832, 7986, 9318 mg/m³ (corresponding to 0.005, 0.063, 0.403, 1.326, 1.596, 2.544, 2.832, 7.986, 9.318 mg/l)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation several times on the day of exposure, further schedule not specified; weighing was performed before exposure, and after 7 and 14 days; if technically applicable, lung function tests of all animals were performed on day 1 and 14 of the observation period in the 1596, 403 and 63 mg/m³ exposure groups.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: lung function (air flow, transpulmonary pressure, dynamic compliance, resistance, functional residual capacity, acetylcholine provocation test); procedures for determination of lung function were performed according to recommendations of Diamond and O'Donnell (1981), Likens and Mauderly (1979), Gross (1981) and Palacek (1969).

Statistics:

Calculation of LC50 according to Rosiello et al. (1977), modified by Pauluhn (1983). Procedure is based on the maximum-likelihood method according to Bliss, Q J Pharm Pharmacol (1938).

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

2.717 mg/L air

95% CL:

2.151 - 3.434

Exp. duration:

4 h

Remarks on result:

other: Corresponding to 2717 mg/m³ air.

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

5.434 mg/L air

Exp. duration:

1 h

Remarks on result:

other: Calculated from 4 h value.

Effect levels 3

Sex:

male/female

Dose descriptor:

other: NOAEC (local effects)

Effect level:

0.005 mg/L air

Exp. duration:

4 h

Remarks on result:

other: Corresponding to 5 mg/m³ air. Respiratory irritation was observed at concentrations of 0.063 mg/mL (corresponding to 63 mg/m³) and above.

Mortality:

Males:
9.318 mg/l: 5/5 (within 3 h);
7.986 mg/l: 5/5 (within 3 to 4 h);
2.832 mg/l: 3/5 (within 4 h to 8 d);
2.544 mg/l: 3/5 (within 24 h to 2 d);
1.596 mg/l: 0/5;
1.326 mg/l: 1/5 (within 4 h);
0.403 mg/l: 0/5;
0.063 mg/l: 0/5;
0.005 mg/l: 0/5;

Females:
9.318 mg/l: 5/5 (within 2 h);
7.986 mg/l: 5/5 (within 3 h);
2.832 mg/l: 0/5;
2.544 mg/l: 4/5 (within 4h to 3 d);
1.596 mg/l: 0/5;
1.326 mg/l: 0/5;
0.403 mg/l: 0/5;
0.063 mg/l: 0/5;
0.005 mg/l: 0/5;

Clinical signs:

other: Number of animals with symptoms (and duration): 9.318 mg/l: 5/5 males and 5/5 females (until death); 7.986 mg/l: 5/5 males (1-4 h) and 5/5 females (1-3 h); 2.832 mg/l: 5/5 males (4 h-15 d) and 5/5 females (4 h-15 d); 2.544 mg/l: 5/5 males (4 h-15 d) an

Body weight:

Reduction of body weight gain beginning at 1.326 mg/l. In rats of the 0.403, 0.063 and 0.005 mg/l exposure groups the body weight gain was comparable to control animals.

Gross pathology:

Deceased animals: necrotic changes in the area of the nose and snout. Extremities showing a yellowish-greenish discolouration. Serous fluids were found in lung an thorax. Lungs were distended and showed liver-like changes. Liver appeared pale, with lobular pattern. Gastrointestinal tract reddened and filled with reddish mucus. Bleached incisives, appearing white.

Other findings:

- Other observations: local effects in the nose and the snout due to the irritating and corrosive character of the test substance.

Analysis of lung function revealed increased lung resistance at day 1 and day 14 after exposure in rats of the 1.596 mg/l exposure group, the authors concluded the occurrence of a progressive obstructive pulmonary damage, mostly impairing the upper and central airways. Strong breathing difficulties persisted during the whole observation period, the pathological investigations supported the indications for respiratory damage (lung edema, pleural effusion, chemical burns).

Rats of the 0.063 mg/l exposure group showed slightly reddened noses on the day of exposure, an impairment of breathing was not observed. From day 1 of the observation period these rats did not show any indications of adverse effects on breathing.

Any other information on results incl. tables

The vapours of thionyl dichlorid revealed a strong irritating potential to the respiratory tract. Due to the high water solubility the vapours mainly damage the upper respiratory tract.

A concentration of 5 mg thionyl dichloride/m³ air caused no clinical symptoms.

Applicant's summary and conclusion

Executive summary:

method: similar to OECD TG 403 Nine groups of male and female Wistar rats, each containing 5 male and 5 female animals, were exposed (nose/head-only) once for 4 hour to different vapor atmospheres of thionylchloride (5, 63, 403, 1326, 1596, 2544, 2832, 7986, 9318 mg/m³). The animals were observed for 14 days after exposure. The vapors of thionyl dichlorid revealed a strong irritating potential to the respiratory tract. Due to the high water solubility the vapors damage the upper respiratory tract and no systemic toxicity is observed. LC50 (male + female rats) = 2717 mg/m³ air. A concentration of 5 mg thionyl dichloride/m³ air caused no clinical symptoms.