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Diss Factsheets

Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report date:
1974

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In a scientifically acceptable and well documented repeated dermal toxicity test, the test substance (50% formulation in water) was administered to the abdominal abraded and intact skin of rabbits.
The dose levels of 125, 250 and 500 mg/kg bw were dermally administrated to two male and two female albino rabbits each (abraded and intact skin). The control group with the same amount of animals received 0.5 mL/kg bw of distilled water in a similar regimen.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Bismuth chloride oxide
EC Number:
232-122-7
EC Name:
Bismuth chloride oxide
Cas Number:
7787-59-9
Molecular formula:
BiClO
IUPAC Name:
chlorobismuthanone
Test material form:
solid
Specific details on test material used for the study:
Appearance: A viscous, silver liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratory Animals, Inc., Denver, Pennsylvania, USA
- Age at study initiation: Adult
- Weight at study initiation: 2.5 to 3.3 kg
- Diet: Purina Rabbit Chow ad libitum
- Water: ad libitum

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on exposure:
TEST SITE
- Area of exposure: Abdominal skin (intact and abraded)
- Type of wrap: Nonabsorbent binder (rubber damming or butcher - paper), gauze, and elastic adhesive tape
- Time intervals for clippings: As necessary, usually once a week

REMOVAL OF TEST SUBSTANCE
- Washing: No

TEST MATERIAL
- Concentration: 50% formulation of the test substance
- Constant volume or concentration used: Yes
- For solids, paste formed: Yes (viscous)

VEHICLE
- Amount applied: 0.5 mL/kg bw
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
24 hours
Frequency of treatment:
Once daily, five days per week for a period of three weeks (Total of 15 applications)
Doses / concentrationsopen allclose all
Dose / conc.:
125 mg/kg bw/day (nominal)
Dose / conc.:
250 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
No. of animals per sex per dose:
2 (abraded and intact skin)
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Observations were recorded once daily for three weeks

DERMAL IRRITATION: Yes
- Time schedule for examinations: Observations were recorded 24 hours after each application and on Sundays (48 hours after the Friday application).

BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were recorded initially, weekly, and terminally.

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Initially and at termination on all control and test animals
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: All
- Parameters checked in table 1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Initially and terminally on all animals
- Animals fasted: No data
- How many animals: All
- Parameters checked in table 2 were examined.

URINALYSIS: Yes
- Time schedule for collection of urine: Initially and terminally on all animals
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table 3 were examined.

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, on all animals at the time of sacrifice by intravenous air embolism on the third day following the last application.
Tissue preservation (see table 4)

HISTOPATHOLOGY: Yes (see table 5)
Statistics:
Statistical analysis of the following parameters was performed by the t-test at the 5.0% probability level; group mean body weight data, hematology data, blood biochemistry data, and urine analysis data.
(Reference: Wilfred J. Dixon and Frank J. Massey, Jr., Introduction to Statistical Analysis, 123-124, McGraw Hill, 1957.)

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, non-treatment-related
Description (incidence and severity):
Grossly, all test groups demonstrated persistent erythema, atonia, and desquamation which the control group failed to demonstrate.
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
Dosages of 0.125, 0.25, and 0.5 g/kg to the intact and abraded skin surface of rabbits resulted in a slight increase in acanthosis and hyperkeratosis in the high dose (0.5 g/kg) rabbits. A variable degree of acanthosis and - hyperkeratosis was noted in rabbits at the lower dose levels and these alterations were generally of comparable severity to those noted in the control group.

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects observed at any dose level.

Target system / organ toxicity

Key result
Critical effects observed:
no

Any other information on results incl. tables

Result tables are provided in the attachment.

Summary

In a scientifically acceptable and well documented repeated dermal toxicity test, the test substance (50% formulation in water) was administered to the abdominal abraded and intact skin of rabbits.

The dose levels of 125, 250 and 500 mg/kg bw were dermally administrated to two male and two female albino rabbits each (abraded and intact skin). The control group with the same amount of animals received 0.5 mL/kg bw of distilled water in a similar regimen.

Generally, all rabbits demonstrated body weight losses over the test period, however, mean body weight of the test groups were comparable to those of the controls at all intervals. All animals essentially appeared normal throughout the study. Signs of dermal irritation included slight to moderate erythema, slight atonia, and slight desquamation with dermal irritation more persistent and varied in the test group as compared to controls.

Results of the clinical studies and gross pathology findings were essentially unremarkable in the test groups as compared to controls.

Microscopically, a slight increase in the incidence of acanthosis and hyperkeratosis of the exposure site was evident in group No. 4 animals (500 mg/kg bw) as compared to controls. All other observations of the test groups were comparable to those of the controls.

Therefore, the NOAEL for dermal repeated toxicity was determined to be 500 mg/kg bw.

Applicant's summary and conclusion