Ammonium thiosulphate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1994-12-01 to 1994-12-15

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Minor deviations without an effect on the results: - The stability of the test item was missing. - The raw data of body weight, pathological findings and clinical signs (two females) were missing in the study report. Narrative descriptions were given for body weight, pathological findings and clinical signs.

Justification for type of information:

see attachment “Read-across concept – Human Health/Environment - Category approach for Inorganic sulfites/thiosulfates/dithionite" in section 13.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987-02-24

Deviations:

yes

Remarks:

, see "Rationale for reliability" above

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Potassium thiosulphate

EC Number:

233-666-8

EC Name:

Potassium thiosulphate

Cas Number:

10294-66-3

Molecular formula:

H2O3S2.2K

IUPAC Name:

dipotassium thiosulfate

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Potassium thiosulfate
- Physical state: Clear light yellow liquid
- Density: 1.47 g/ml

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Myrtle's Rabbitry, Thompson Station, TN
- Housing: The animals were housed individually in suspended stainless steel cages. All housing and care were based on the standards recommedned by the Guide for the Care and Use of Laboratory Animals (Guide for the Care and Use of Laboratory Animals, DHHS Publication No. (NIH) 86 - 23, 1985.)
- Diet (ad libitum): Purina Certified Rabbit Chow #5322
- Water (ad libitum): Municipal tap water treated by reverse ososis
- Quarantine period: A minimum of five days (Animals were examined on arrival. All animals received a detailed pretest observation prior to dosing. only healthy animals were chosen for study use.)

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 22.2 °C
- Relative humidity: 30 - 67%
- Air changes: Ten to twelve air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: On Day-1, the fur was removed from the dorsal trunk area of the animals chosen for the limit test using an animal clipper. The clipped area was ≥ 10% of the animal's body surface area (BSA). Care was taken to avoid abrading the skin during the clipping procedure. On the following day (day 0), the test article was administered dermally to approximatley 10 % of the body surface area (BSA). The BSA was calculated for each animal using the formula [BSA in cm^2 = 9 X (body weight in grams)^0.66667] and the four corners of this area were delineated in the clipped area with an indelible marker. The test article was spread evenly over the delineated test area.
- Type of wrap if used: The test substance was held in contact with the skin with an appropriately sized 4 ply porous gauze dressing backed with plastic wrap (occlusive binding). Removal and ingestion of the test article was prevented by placing an elastic wrap over the trunk and test area. The elastic wrap was further secured with adhesive tape around the trunk at the cranial and caudal ends. After dosing, collars were placed on the animals and remained in place until removal on study day 3.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After approximately 24-hour exposure period, the gauze dressing, plastic and elastic wrap were removed and the corners of the test site delineated using a marker. Residual test article was removed using gauze moistened with distilled water.

TEST MATERIAL
The test article was administered as received from the Sponsor.
- Amount(s) applied (volume or weight with unit): Individual doses were calculated based on the animal's day 0 body weight.
- Concentration: 100 %
- Constant volume or concentration used: Yes

Duration of exposure:

Approximately 24 hour

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males / 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Limit test animals were observed for clinical abnormalities two times on study day 0 (postdose) and daily thereafter (days 1-14). A mortality check was performed twice daily, in the morning and afternoon.Limit test animals were examined for erythema and oedema following patch removal on study day 1 and daily thereafter (days 2-14) according to te Dermal Grading System based on Draize (Draize, J.H., Appraisal of the Safety of Chemcicals in Foods, Drugs and Cosmetics, The Association of Food and Drug Officials of the United States, 49-51, 1959.). The dermal test sites were reclipped as necessary to allow clear visualization of the skin. Individual body weights were obtained for the limit test animals prior to dosing on day 0 and on days 7 and 14.
- Necropsy of survivors performed: Yes, all limit test animals were euthanized (intravenous injetion of sodium pentobarbital) at study termination (day 14) and necropsied. Body cavities (cranial, thoracic, abdominal and pelvic) were opened and examined. No tissues were retained.

Statistics:

Data from the limit test were analyzed and an LD50 value estimated as follows:
< 50 % Mortality: LD50 was estimated as greater than the administered dose
= 50 % Mortality: LD50 was estimated as equal to the administered dose
> 50 % Mortality: LD50 was estimated as less than the administered dose.
Body weight means and standard deviatio n were calculated separately for males and females for each limit level administered.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The LD50 was estimated.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The LD50 was estimated.

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The LD50 was estimated.

Mortality:

No mortality occurred during the limit test.

Clinical signs:

other: The most notable clinical abnormalities observed during the study included transient incidences of fecal stain. Dermal irritation was noted at the sites of test article application.

Gross pathology:

No significant gross internal findings were observed at necropsy on study day 14. Two incidences of cyst(s) on the oviduct(s) were observed; however, these findings were not considered significant since they are commonly found in rabbits of this strain.

Other findings:

No data

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this test, the acute dermal LD50 of potassium thiosulfate was estimated to be greater than 2000 mg/kg in the rabbit.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic by the dermal route.