[No public or meaningful name is available]

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 22 February, 1988 to 24 March, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Toxic Substances Control Act (TSCA) acute dermal toxicity guideline

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, coco alkyltrimethyl, chlorides

EC Number:

263-038-9

EC Name:

Quaternary ammonium compounds, coco alkyltrimethyl, chlorides

Cas Number:

61789-18-2

Molecular formula:

C(n+3) H(2n+10) N Cl (n=8-18)

IUPAC Name:

Quaternary ammonium compounds, cocoalkyl trimethyl, chloride

Constituent 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Dihydrogen oxide

Test material form:

liquid

Specific details on test material used for the study:

- Physical state: Clear yellow liquid
- Analytical purity: 33%
- Lot/batch No.: 1735305
- Storage condition of test material: Sealed container at 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: Mochican Valley Rabbitry, Loidonville, Ohio
- Weight at study initiation: 2140 to 2990 g
- Housing: individual suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified rabbit chow # 5322, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Minimum 7 d

ENVIRONMENTAL CONDITIONS
- Humidity (%): 49-74%
- Photoperiod (h dark / h light): 12 h / 12 h

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: Shaved intact dorsal skin
- % coverage: 20%
- Type of wrap if used: Test substance was applied under gauze binders that were secured with non-irritating tape.

Duration of exposure:

24 h

Doses:

0, 520, 1020 and 2000 mg/kg bw.

No. of animals per sex per dose:

Five animals per sex per test group, three animals per sex in control group.

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: Animals were observed at 1, 3 and 4 h post-dosing on Day 0 and twice daily for mortality and once daily for clinical observations for 14 d. Application sites were examined for erythema, oedema and other dermal findings at 30−60 min after bandage removal and daily thereafter for 13 d. Erythema and oedema were graded according to Draize method.
- Frequency of observations and weighing: Day 0, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

LD50 and slopes (with 95% confidence limits) were calculated by method of Litchfield and Wilcoxon.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 1 300 mg/kg bw

Based on:

test mat.

95% CL:

ca. 800 - ca. 1 900

Remarks on result:

other: i.e., equivalent to 429 mg a.i./kg bw

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 1 900 mg/kg bw

Based on:

test mat.

95% CL:

ca. 1 500 - ca. 2 400

Remarks on result:

other: i.e., equivalent to 627 mg a.i./kg bw

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 600 mg/kg bw

Based on:

test mat.

95% CL:

ca. 1 200 - ca. 2 100

Remarks on result:

other: i.e., equivalent to 588 mg a.i./kg bw

Mortality:

Control: 0/6 animals
520 mg/kg bw: 0/10 animals
1020 mg/kg bw: 2/5 males and 0/5 females
2000 mg/kg bw: 4/5 males and 3/5 females

Clinical signs:

other: Lethargy and ataxia were major clinical findings. Other findings included hypothermia, decreased respiratory rate, laboured respiration, nasal discharge, decreased defecation, emaciation, red staining around the mouth, diarrhoea.

Gross pathology:

Treatment-related abnormality on the application sites of all rabbits. No substance-related internal abnormalities in rabbits that died during study or terminally sacrificed.

Other findings:

Test substance induced moderate to severe erythema and oedema with other significant dermal findings such as necrosis, desquamation, scabbing, eschar, exfoliation, fissuring and blenching. Subcutaneous haemorrhage was present on the application sites of one rabbit in the 2000 mg/kg bw group that survived and all animals that died.

Any other information on results incl. tables

Only (systemic) pathology observed in animals sacrificed at termination were kidney abnormalities (pale, reddened, pitted) in 5/21 of the terminally sacrificed dosed rabbits. Pale kidneys were also observed for one female in the control group. The skin of the animals that died showed eschar, subcutaneous haemorrhage, blanching and thickening. Internal abnormalities included hemorrhagic thymus glands (6/9) (typical agonal change), red foci or dark red area in the stomach (3/9), brain haemorrhages (3/9) and liver soft or pale and soft (2/9). No internal abnormalities were observed among rabbits that died which could be attributed to the test substance. There were no test substance related internal changes for rabbits that were terminally sacrificed.

Considering the generally low dermal absorption of Coco TMAC (<10% in Bartnik and Wingen, 1979 study), it is likely that severe corrosive effects upon the 24 h exposure of the concentrated product were more cause to the death of the animals, than real systemic toxicity. This is supported by the relatively limited observations on internal organs upon necropsis of the animals that died. The most commonly observed internal abnormalities were hemorrhagic thymus glands (6/9), which is a typical agonal change, and likely not a specific sign of toxicity.

Applicant's summary and conclusion

Interpretation of results:

other: Category 3 based on CLP criteria

Conclusions:

Under the conditions of the test, the acute dermal LD50 for male and female albino rabbits were determined to be 1,300 mg/kg bw (i.e., equivalent to 429 mg a.i./kg bw) and 1,900 mg/kg bw (i.e., equivalent to 627 mg a.i./kg bw) respectively, and the combined dermal LD50 was determined to be 1,600 mg/kg bw (i.e., equivalent to 528 mg a.i./kg bw).

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance, Coco TMAC (active ingredient 33%), in albino rabbits according to OECD 402 Guideline, in compliance with GLP. The test substance at 0, 520, 1,020 or 2,000 mg/kg bw was applied under semi-occlusive conditions for 24 h in a single application to the shaved, intact skin of groups of 10 rabbits (five per sex). Animals were observed at 1, 3 and 4 h post-dosing. Following the 24 h exposure period, animals were observed for mortality, clinical signs and skin response for 14 d. There was no mortality in the control or 520 mg/kg bw group. Two males died in the 1,020 mg/kg bw group while 4 males and 3 females died in the 2,000 mg/kg bw group. Under the conditions of the test, the acute dermal LD50 for male and female albino rabbits were determined to be 1,300 mg/kg bw (i.e., equivalent to 429 mg a.i./kg bw) and 1,900 mg/kg bw (i.e., equivalent to 627 mg a.i./kg bw) respectively, and the combined dermal LD50 value for males and females was determined to be 1,600 mg/kg bw (i.e., equivalent to 528 mg a.i./kg bw). Considering the generally low dermal absorption potential of Coco TMAC (<10% in Bartnik and Wingen, 1979 study), the observed systemic effects and mortality were attributed to the severe corrosive properties of the test substance following 24 h exposure rather than real systemic toxicity. This is supported by the relatively limited observations on internal organs upon necropsis of the animals that died (Naas, 1988).