Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Start : 30 January 2002 End : 13 February 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: There are no deviations from the recommended guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Phenyloxindole
- Physical state: Light beige powder
- Analytical purity: 99.80%
- Lot/batch No.: CHAD 9902K
- Expiration date of the lot/batch: 14 November 2002 (allocated by NOTOX, 1 year after receipt of the test substance)
- Storage condition of test material: At room temperature in the dark

Test animals

Species:
rat
Strain:
other: Wistar strain Crl:(WI) BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sillzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: males: 341-378 g; females: 205-253 g
- Housing: lndividually housed in labelled polycarbonate cages (type III, height 15 cm.) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany)
- Diet (e.g. ad libitum): Standard pelleted laboratory animal diet (from Altromin (code VRF 1) , Lage, Germany), ad libitum.
- Water (e.g. ad libitum): Tap water, ad libitum.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3ºC
- Humidity (%): 30-70%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours dark per day.


IN-LIFE DATES: Start : 30 January 2002; End : 13 February 2002

Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 25 cm2 for males and 18 cm2 for females.
- % coverage: 10% of the total body surface.
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D),
successively covered with aluminium foil and Coban flexible bandagee. A piece of Micropore tape was additionally used for fixation of the bandages in females only.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was removed using water.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (10 ml/kg)


Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Observations were performed at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales. No observation for clinical signs was performed on day 2 of the study. Since sufficient information on clinical signs was availabie, this protocol deviation was considered not to have affected the study integrity. Body weights were recorded on Days 1 (pre-administration), 8 and 15.

- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was required.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
One female showed chromodacryorrhoea between days 6 and 13. No further signs of systemic toxicity were noted among the animals.
Erythema and scales were seen on the back of one female between days 4 and 9.
Body weight:
The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
The incidence of slight body weight loss between days 1 and 8 in individual animals was considered not indicative of toxicity, based on the absence of any corroborative findings in these animals.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

Table 7.2.3:      Summary of Acute Dermal Toxicity

Males

Females

Dose

Mortality

Time of death

Dose

Mortality

Time of death

2000 mg/kg bw

0/5

--

2000 mg/kg bw

0/5

--

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of Phenyloxindole in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Phenyloxindole was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. One female showed chromodacryorrhoea between days 6 and 13. No further signs of systemic toxicity were noted among the animals. Erythema and scales were seen on the back of one female between days 4 and 9. The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal in treated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination. The dermal LD50 value of Phenyloxindole in Wistar rats was established to exceed 2000 mg/kg bw.