Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to Guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)
Deviations:
yes
Remarks:
Deficiencies in biochemical and haematological data; Application only twice per week. (Study was conducted before the implementation of OECD 411)
GLP compliance:
no
Remarks:
GLP not mandatory at that time.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): trade name
- Physical state: paste
- Purity: 30.1%
- Lot/batch No.: CP 3515/6B

Test animals

Species:
mouse
Strain:
C57BL
Sex:
male/female
Details on test animals and environmental conditions:
- Housing: Individual cages on sawdust
- Diet: pelleted diet ad libitum
- Water: ad libitum

Administration / exposure

Type of coverage:
not specified
Vehicle:
water
Details on exposure:
0.2 mL of an aqueous solution were applied twice weekly.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
No data
Frequency of treatment:
Twice weekly
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 5, 10, 12.5, 15% a.s.
Basis:
other: nominal
Remarks:
Doses / Concentrations:
0, 200, 400, 500 and 600 mg/kg bw/day
Basis:
other: Based on an average weight of 20 g/mouse and a 5 days/week treatment.
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
The mice were weighed weekly, and their water intakes determined twice weekly by subtracting the amount left from that given.
Sacrifice and pathology:
At necropsy the liver, spleen, kidneys, heart, brain and testes were removed and weighed. Blocks of these and various tissues were reserved for histological examination.
Other examinations:
After 13 weeks skin blood samples were taken by cardiac puncture. The blood samples were used for haematological estimations - packed cell volume, haemoglobin level, mean corpuscular haemoglobin concentration and white cell count.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY
One mouse treated with 12.5% died after 1 week due to dehydration and anorexia.

WATER CONSUMPTION
At 10% and above the water intake was increased.

HAEMATOLOGY
Haemoglobin levels reduced and wbc counts increased in high dose males.

ORGAN WEIGHTS
Absolute and relative heart weights were higher in high dose females. Relative liver weights were increased in both sexes at the 15% and in females at the 12.5% concentration. Increased absolute kidney weights (males) and relative kidney weights (females) were found at the 15% dose level.

GROSS PATHOLOGY & HISTOPATHOLOGY
Exudate adherent to skin (4/20) was observed at the 15% dose level. Loss of hair colour lateral and ventral to application site observed at all treatment levels. Extensive ulceration and necrosis of the epidermis of the decedent at the 12.5% treatment level. Dose-related ulceration of the epidermis (4/20) with inflammatory exudate (11/20) observed at 15% and 12.5% treatment levels.

OTHER FINDINGS
At concentrations of 12.5 and 15%, cytotoxic effects were found in the epidermis.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
10 other: %
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: Corresponding to 400 mg/kg bw.
Dose descriptor:
LOAEL
Effect level:
12.5 other: %
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: Extensive necrosis and ulceration of the skin, changes in haematology and organ weights.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion