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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD test guideline, with acceptable restrictions. The restrictions were limited reporting of test substance information and animal experimental conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
New Zealand white rabbits, weighing between 2.0 and 3.0 kg, were used.
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 2.0-3.0 kg
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data


IN-LIFE DATES: No data

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Rabbits were immobilized during a 24-hour contact period.  The test material was retained under impervious sheeting on the clipped, intact skin of the trunk. After the contact period, excess fluid was removed to diminish ingestion. 
Duration of exposure:
24 hours
Doses:
4.0, 2.0, and 1.0 mL/kg
No. of animals per sex per dose:
4/sex/dose
Control animals:
no
Details on study design:
 Observations for skin reaction were made at one hour, 7 days and 14 days after the contact period.

Animal weights were recorded at 0 days (before dose), 7 days and 14 days (just prior to sacrifice).  At death or sacrifice, each animal was subjected to gross pathologic evaluation.  
Statistics:
LD50's were calculated by the moving average method (Thompson, 1947) and were based on a 14-day observation period.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
2.38 mL/kg bw
95% CL:
1.56 - 3.63
Sex:
female
Dose descriptor:
LD50
Effect level:
1.78 mL/kg bw
95% CL:
0.838 - 3.79
Mortality:
Males: 4/4, 1/4, and 0/4 at 4.0, 2.0, and 1.0 mL/kg, respectively
Females: 4/4, 2/4, and 1/4 at 4.0, 2.0, and 1.0 mL/kg, respectively
Clinical signs:
MALES:
Dosage: 4.0 ml/kg
Signs of Toxicity: Immediate signs of discomfort; prostration before death; death of 1 at 30 min.

Dosage: 2.0 ml/kg
Signs of Toxicity: Immediate signs of discomfort; sluggishness, unsteady gait at 1 day. Survivors recovered at 2 days.

Dosage: 1.0 ml/kg
Signs of Toxicity: Immediate signs of discomfort

FEMALES
Dosage: 4.0 ml/kg
Signs of Toxicity: Immediate signs of discomfort; 1 with sluggishness, unsteady gait at 1 day.

Dosage: 2.0 ml/kg
Signs of Toxicity: Immediate signs of discomfort; sluggishness, unsteady gait at 1 day; victims with diarrhea, weak appearance at 7 days.

Dosage: 1.0 ml/kg
Signs of Toxicity: None noted
Body weight:
MALES:
Dosage: 4.0 ml/kg
Weight Change (g): all animals died

Dosage: 2.0 ml/kg
Weight Change (g): 7 days = -495 to -259; 14 days = -589 to 127

Dosage: 1.0 ml/kg
Weight Change (g): 7 days = -190 to -29; 14 days = -60 to 138

FEMALES
Dosage: 4.0 ml/kg
Weight Change (g): all animals died

Dosage: 2.0 ml/kg
Weight Change (g): 7 days = -861 to -185; 14 days = -97 to -1

Dosage: 1.0 ml/kg
Weight Change (g): 7 days = -379 to -172; 14 days = -320 to 76
Gross pathology:
MALES:
Dosage: 4.0 ml/kg
Gross Pathology: Livers with multiple tan patches

Dosage: 2.0 ml/kg
Gross Pathology: In victim, lungs with maroon and pink patches. In 1 survivor, lungs discolored; in another, liver
discolored.

Dosage: 1.0 ml/kg
Gross Pathology: Liver of 1 adhered to abdominal wall


FEMALES
Dosage: 4.0 ml/kg
Gross Pathology: Livers with tan patches; urine of 1 dark brown; abdominal cavity of 1 contained red fluid.

Dosage: 2.0 ml/kg
Gross Pathology: In victims, livers with red patches or tan foci. One survivor, with caecum adhering to peritoneal lining.

Dosage: 1.0 ml/kg
Gross Pathology: Nothing remarkable
Other findings:
MALES:
Dosage: 4.0 ml/kg
Skin Irritation: Edema, necrosis

Dosage: 2.0 ml/kg
Skin Irritation: Necrosis at 1 day; erythema, necrosis,
desquamation at 14 days

Dosage: 1.0 ml/kg
Skin Irritation: Necrosis at 1 day; erythema, edema,
necrosis, desquamation, scabs at 14 days.

FEMALES
Dosage: 4.0 ml/kg
Skin Irritation: Necrosis

Dosage: 2.0 ml/kg
Skin Irritation: Erythema, necrosis at 1 day; necrosis,
desquamation at death or sacrifice.

Dosage: 1.0 ml/kg
Skin Irritation: Erythema, necrosis at 1 day; erythema,
necrosis, desquamation, scabs at 14 days

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a well-reported acute dermal toxicity study conducted using a protocol similar to OECD test guideline 402 (of unknown GLP status), the LD50 for Organochlorosilane A-161 was 2.38 ml/kg for males and 1.78 ml/kg for females.
Executive summary:

In a well-reported acute dermal toxicity study conducted using a protocol similar to OECD test guideline 402 (of unknown GLP status), Organochlorosilane A-161 was applied (1, 2 or 4 ml/kg), under an occlusive dressing, to the shaved, intact skin of New Zealand white rabbits (4/sex/dose) for 24 hours. After the exposure period, excess test substance was removed. Severe skin irritation was associated with the exposures. Observations for skin reactions were made at one hour, seven days and 14 days post-exposure. Signs of toxicity included evidence of discomfort (vocalisation, hyperactivity), sluggishness and unsteady gait. At necropsy the lungs and livers were discoloured. The LD50s were 2.38 and and 1.78 ml/kg for male and female rabbits, respectively.