Registration Dossier

Diss Factsheets

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:
1975
Report date:
1975

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
Deviations:
yes
Remarks:
Two animals per sex and per dose had their skin abraded. No indication if the substance was held in contact with the skin.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Hexachlorocyclopentadiene
EC Number:
201-029-3
EC Name:
Hexachlorocyclopentadiene
Cas Number:
77-47-4
Molecular formula:
C5Cl6
IUPAC Name:
hexachlorocyclopentadiene

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: not specified
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: adult
- Weight at study initiation: From 2 to 3 kg
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified

Administration / exposure

Type of coverage:
not specified
Vehicle:
ethanol
Details on exposure:
TEST SITE
- Area of exposure: back
- % coverage: 20
- Type of wrap if used: not specified
- Time intervals for shavings or clipplings: one week but more often if necessary

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified
- Time after start of exposure: not specified

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 mL/kg
- Concentration (if solution): 0.1% w/v or 0.5% w/v
- Constant volume or concentration used: yes

VEHICLE
- Justification for use and choice of vehicle (if other than water): not specified
- Purity: not specified

USE OF RESTRAINERS FOR PREVENTING INGESTION: yes
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
Once a day, 5 days a week.
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
1 mg/kg bw/day (nominal)
Dose / conc.:
5 mg/kg bw/day (nominal)
No. of animals per sex per dose:
5 animals/sex/dose (including 2 animals/sex/dose with abraded skin).
Control animals:
yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Prior to the start of the study and at Day 23 of the study
- Anaesthetic used for blood collection: No data
- Animals fasted: Yes
- How many animals: All animals

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Prior to the start of the study and at Day 23 of the study
- Animals fasted: Yes
- How many animals: All animals

URINALYSIS: Yes
- Time schedule for collection of urine: At Day 23 of the study
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes
Statistics:
Not specified

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
The test substance was severely irritating to the skin upon repeated dermal application at both concentration tested.
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Non significant body weight losses were noted in some animals treated at 5 mg/kg bw/d.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
Statically significant organ weight differences were observed between the groups but the results were within the historical data of the laboratory for rabbits of this strain and age. These differences were attributed to grouping and the small number of animals.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Gross skin changes were observed consisting of fibrosis, escharosis and slight to severe desquamation for both treated groups. No systemic effects were observed.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Microscopic examination of the test skin sites revealed acanthosis and hyperkeratosis involving the epidermis in a few animals treated at 1 mg/kg bw/d and most animals treated at 5 mg/kg bw/d. An associated inflammation of the dermis escharosis formation, epidermal ulceration or microabscessation were also observed in some animals. No systemic effects were observed.
Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
> 5 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical biochemistry
clinical signs
gross pathology
haematology
histopathology: neoplastic
histopathology: non-neoplastic
mortality
organ weights and organ / body weight ratios
urinalysis
Key result
Dose descriptor:
LOAEL
Remarks:
local
Effect level:
1 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
dermal irritation
gross pathology
histopathology: non-neoplastic

Target system / organ toxicity

Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
1 mg/kg bw/day (nominal)
System:
integumentary
Organ:
skin
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
yes

Applicant's summary and conclusion

Conclusions:
This short-term toxicity study by the dermal route performed on the registered substance allowed to determine a NOAEL(systemic) of 5 mg/kg bw/day and a LOAEL(local) of 1 mg/kg bw/day. The skin was the only identified target organ.
Executive summary:

The repeated dose toxicity of Hexachlorocyclopentadiene by the dermal was evaluated using a method similar to the OECD Test Guideline 410 (non-GLP) with deviations.

Rabbits received applications of 0, 1 or 5 mg/kg bw of Hexachlorocyclopentadiene once a day, 5 days per week, for 4 weeks. Mortality, clinical signs and body weight were recorded. Haematology, blood chemistry and urinalysis were investigated. At the end of the study, surviving animals were subjected to gross necropsy and histopathology.

No mortality was observed as a result of this study. No systemic effects including significant variation of the body weight of treated animals were observed.

The test substance was severely irritating to the skin upon repeated dermal application at both concentrations tested. These findings were confirmed during the gross pathology and histopathology examination. Gross skin changes were observed consisting of fibrosis, escharosis and slight to severe desquamation for both treated groups. Microscopic examination of the test skin sites revealed acanthosis and hyperkeratosis involving the epidermis in a few animals treated at 1 mg/kg bw/d and most animals treated at 5 mg/kg bw/d. An associated inflammation of the dermis escharosis formation, epidermal ulceration or microabscessation were also observed in some animals

There was no change in the blood and urine parameters at the end of the study.

This short-term toxicity study by the dermal route performed on the registered substance allowed to determine a NOAEL(systemic) of 5 mg/kg bw/day and a LOAEL(local) of 1 mg/kg bw/day. The skin was the only identified target organ.