3,3'-thiodi(propionic acid)

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

3,3'-thiodi(propionic acid)

EC Number:

203-841-3

EC Name:

3,3'-thiodi(propionic acid)

Cas Number:

111-17-1

Molecular formula:

C6H10O4S

IUPAC Name:

3-[(2-carboxyethyl)sulfanyl]propanoic acid

Details on test material:

- Name of test material (as cited in study report): 3,3´-Thiobispropanoic acid
- Analytical purity: 99.5 %
- Lot/batch No.: MB-311

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent.
- Age at study initiation: approximately eight to twelve weeks old
- Weight at study initiation: weight range of 200g to 350g
- Fasting period before study:
- Housing: The animals were housed in groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood f akes (Datesand Ltd., Cheshire, UK) and provided with environmental enrichment items: wooden chew blocks (B & K Universal Ltd, Hull, UK) and cardboard “fun tunnels” (Datesand Ltd., Cheshire, UK).
- Diet (e.g. ad libitum)+ Water (e.g. ad libitum): With the exception of the exposure period, free access to mains drinking water and food (EU Rodent Diet 5LF2, BCM IPS Limited, London, UK) was allowed throughout the study.

- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°C
- Humidity (%): 30 - 70%
- Air changes (per hr): fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light and twelve hours darkness

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure chamber volume: approximately 30 litres (dimensions: 28 cm diameter x 50 cm high)
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier
of the exposure chamber and sealed by means of a rubber ‘O’ ring. Only the nose of each animal was exposed to the test atmosphere.
- Method of conditioning air: Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the SAG 410.
- System of generating particulates/aerosols: A dust atmosphere was produced from the test material using a SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany) located adjacent to the exposure chamber. The SAG 410 was connected to a metered compressed air supply. A particle separator was introduced before the aerosol entered the exposure chamber in order to remove large particles and thereby increase the inhalable por ion of the generated aerosol.
- Method of particle size determination: Marple Personal Cascade Impactor (Westech IS Ltd, Beds., UK).
- Temperature, humidity, pressure in air chamber: The environmental controls were set to achieve values of 19 - 25°C and 30 - 70% relative
humidity.

Duration of exposure:

4 h

Concentrations:

5.13 mg/L

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.13 mg/L air

Exp. duration:

4 h

Mortality:

One animal showed a rapid decline in condition on Day 10 and was subsequently humanely killed, this animal exhibited significant weight loss and observations now included decreased respiratory rate, laboured respiration, noisy respiration, lethargy, hunched posture, piloerection and red/brown staining around the snout.

Clinical signs:

other: During exposure, there were frequent instances of increased respiratory rate. On removal from the chamber, animals showed increased respiratory rate and noisy respiration. One hour after removal, no change in the condition of the animals was observed. One

Body weight:

All male animals exhibited bodyweight loss or reduced bodyweight gain during Week 1, four of these animals recovered to show normal development during Week 2. Normal bodyweight development was noted for all female animals during the study.

Gross pathology:

Apart from one instance of dark patches on the lungs no macroscopic abnormalities were detected amongst animals that survived until Day 14 at necropsy.

Any other information on results incl. tables

Mortality Data:

Mean Achieved Atmosphere Concentration (mg/L)	Deaths:
	Male	Female	Total
5.13	1/5	0/5	1/10

Only one death occurred in a group of ten rats exposed to a mean achieved atmosphere

concentration of 5.13 mg/L for four hours. It was therefore considered that the acute inhalation

median lethal concentration (4 hr LC50) of TDPA, in the Sprague-Dawley Crl:CD® (SD) IGS BR

strain rat, was greater than 5.13 mg/L.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute inhalation toxicity study according to OECD TG 403 Sprague-Dawley rats (5/sex) were exposed to 5.13 mg/L air 3,3'-Thiobispropanoic acid (nose only; dust) for 4 h. Animals were then observed for 14 d.
One animal showed a rapid decline in condition on Day 10 and was subsequently humanely killed, this animal exhibited significant weight loss and observations now included decreased respiratory rate, laboured respiration, noisy respiration, lethargy, hunched posture, piloerection and red/brown staining around the snout.
During exposure, there were frequent instances of increased respiratory rate. On removal from the chamber, animals showed increased respiratory rate and noisy respiration. One hour after removal, no change in the condition of the animals was observed. One day after exposure, all animals exhibited increased respiratory rate, hunched posture and piloerection. There were frequent instances of noisy respiration and red/brown staining around the head. The majority of animals showed good signs of recovery over the recovery period, one animal exhibited a scab on the head on Days 8 and 9 but this was not considered to be treatment related. Female animals recovered quicker than male animals such that they appeared normal from Days 3 to 8 post-exposure. Three out of the four surviving male animals appeared normal from Days 5 to 12, however, one male animal still exhibited noisy respiration by Day 14.
All male animals exhibited bodyweight loss or reduced bodyweight gain during Week 1, four of these animals recovered to show normal development during Week 2. Normal bodyweight development was noted for all female animals during the study.
Apart from one instance of dark patches on the lungs no macroscopic abnormalities were detected amongst animals that survived until Day 14 at necropsy.
The 4 h LC50 was 5.13 mg/L air.