2-ethylhexyl 10-ethyl-4,4-dimethyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline-type study, conducted under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Remarks:

none that affected the results of the study

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexyl 10-ethyl-4,4-dimethyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

EC Number:

260-829-0

EC Name:

2-ethylhexyl 10-ethyl-4,4-dimethyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

Cas Number:

57583-35-4

Molecular formula:

C22H44O4S2Sn

IUPAC Name:

2-ethylhexyl 2-{[({2-[(2-ethylhexyl)oxy]-2-oxoethyl}sulfanyl)dimethylstannyl]sulfanyl}acetate

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Western Oregon Rabbit Company (Philomath, OR).
- Age at study initiation: 11 to 12 weeks
- Weight at study initiation: 2.25 to 2.78 kg for males and 2.32 to 2.81 kg for females.
- Fasting period before study: Recorded in raw data.
- Housing: The animals were housed individually in stainless steel cages suspended above noncontact bedding pans containing Sani-Chips hardwood bedding (P.J. Murphy Forest Products, Montville, NJ).
- Diet (e.g. ad libitum): Rabbits received a daily ration of Purina Certified High-Fiber Rabbit Chow Type 5325 (Richmond, IN)
- Water: ad libitum. All rabbits had free access to purified (filtered, deionized, and UV-treated) tap water via automatic watering:
- Acclimation period: 7 day quarantine period


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19- 21
- Humidity (%): 36 – 67%
- Air changes (per hr): 10 air changes per hour with no recirculation
- Photoperiod (hrs dark / hrs light): 12 – hour on and 12 hour off


IN-LIFE DATES: From: March 25, 1993 To: April 8, 1993

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Two days before treatment, 10 male and 10 female rabbits were randomly selected from a healthy stock population and tentatively assigned to the study. The fur was clipped free from the dorsal area of the trunk of the selected rabbits by the use of electric clippers (Oster, Milwaukee, WI) with a size 40 blade. One day before treatment, the clipping was repeated. Care was taken to avoid abrading the skin, and only animals with healthy, intact skin were selected. Extra animals from the same shipment were available as substitutes for any animal assigned to the study that had unacceptable skin.
- % coverage: The test substance was applied uniformly within a 12 X 14 cm (168-cm-2) area of clipped intact skin.
- Type of wrap if used: Elastikon tape (Johnson & Johnson Products, Inc. New Brunswick, NJ).


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The application sites were washed with a few milliliters (exact amount was not measured) of 1% (v/v) aqueous solution of Ivory® Liquid Hand Soap (Lot No. 2202 K 103; Proctor & Gamble, Inc., Cincinnati, OH). The soap was removed from the application sites by rinsing under a stream of running lukewarm tap water. The animals were then blotted dry with paper towels and returned to their respective cages.
- Time after start of exposure: 24-hour exposure period.


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.89 ml/kg
- Concentration (if solution): Dose level of 1.05 g/kg
- Constant volume or concentration used: No, Use of the density measured by SRI, the volume dose was calculated.
- For solids, paste formed: NA, test material was liquid


VEHICLE
- Amount(s) applied (volume or weight with unit): 0.89 ml/kg of saline (0.9% Sodium Chloride
- Concentration (if solution): 0.9%
- Lot/batch no.: Lot No. G869024, Baxter Health Care Corp., Deerfield, IL).
- Purity: 0.9% Sodium Chloride

Duration of exposure:

24 hours

Doses:

1050 mg/kg

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations done at 0.00 hr to 1:11 hr; 1:45 to 2:56 hr; 2:25 to 3:36 hr; and 3:55 to 5:06 hr. Body weights were recorded on Day 0 (before dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: No deaths, or test substance-related systemic effects were observed over the 14-day observation period. After removal of the screen and patches, the applications sites of 9 of the ten rabbits had a slight oily film; after washing and rinsing, one of 10 rabbits had no visible residue, and 9 of 10 had “no appreciable film” visible. Of those nine animals, three required a second rinse. The only observation of an effect other than skin irritation was a single observation of “hyperactivity’ in one treated female on Day 9. Because this effect was observed in only one animal, and the effect occurred relatively late in the study, the effect is judged to be incidental and not related to treatment with the test substance. All male and female rabbits had varying degrees of skin irritation. Males and females in both the treated and control groups showed transient irritation for the “non-irritating” tape at the perimeter of the application site. Males and females in the treated group showed additional irritation responses, such as thickened skin and chapped and flaky skin within the application site beginning as early as Day 2; all animals had recovered by Day 12. Because the contact period was 24 hr (compared to 4 hr for a dermal irritation assessment; e.g. 40 CFR 798.4470), these observations should not be used to evaluate the primary irritation potential of the test substance.

Statistics:

Other than the calculation of the mean and standard deviations for the body weights, no statistical evaluations were conducted.

Results and discussion

Preliminary study:

Before animal studies were initiated, preliminary work was conducted to verify that the test substance coudl be washed from the surface with a 1% aqueous solution of Ivory (R) Lilquid Hand Soap. Samples of polypropylene screen were placed in aliquots of the test substance for 25 hr at room temperature, and were found to increase their weight by less than 3%. These preliminary data indicated that the screen would be compatible with the test substance and that the proposed method of washing the apploication sites after the 24-hr contact period would be effective.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 050 mg/kg bw

Mortality:

No deaths were observed over the 14-day observation period.

Clinical signs:

other: There were no treatment-related systemic clinical signs. The only observation of an effect other than skin irritation was a single observation of “hyperactivity” in one treated female on Day 9. Because this effect was observed in only one animal, and th

Gross pathology:

Necropsy revealed a slightly rough outer surface of the spleen of one treated male. The observation is judged to be incidental and to have no obvious relationship to treatment with the test substance.

Other findings:

Skin effects in the rabbits included the following observations: Irritation around the perimeter of the application site, redness, thickened skin, chapped, flaky skin, and edema.

Applicant's summary and conclusion

Interpretation of results:

other: coudl not be determined as the result is an inequality

Conclusions:

Based on the lack of observed mortality, the 14-day acute dermal LD50 of the test substance was reported as >1050 mg/kg for both sexes.

Executive summary:

The acute dermal toxicity of the test substance was assessed by applying the liquid test substance within a 12 x 14 cm are of clipped intact skin of five male and five female New Zealand White rabbits at 1050 mg/kg body weight. The application site was covered with a 4 -ply 15 x 15 cm gauze patch held in place by nonirritating tape and polypropylene screen for 24 hours, after which the patch and the screen were removed. The application sites were washed with a dilute soap solution, rinsed with water, then blotted dry. A control group of five males and five females was treated with 0.89 mL/kg of saline and were handled in the same way as the animals that received the test substance. No deaths, or test substance related systemic effects were observed over the 14 -day observation period. The only systemic clinical sign was a single observation of hyperactivity in one treated female on Day 9. Because this effect was observed in only one animal, and the effect occurred relatively late in the study, the effect is judged to be incidental and not related to treatment with the test substance. All male and female rabbits had varying degrees of skin irritation. Males and females in both the treated group showed additional irritation responses such as thickened skin, edema, and chapped and flaky skin beginning as early as Day 2; all animals had recovered by Day 12. Because the contact period was 24 hr (compared to 4 hr for a dermal irritation assessment), these observations should not be used to evaluate the primary irritation potential of the test substance. There were no apparent body weight effects. Necropsy revealed no treatment related effects. Under the conditions of this study, the acute dermal LD50 in male and female rabbits was greater than 1050 mg/kg.