Registration Dossier

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:
1991-02-06 to 1991-02-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted February 24, 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
EEC Directive 84/449 EEC, EEC Publication No. L251, September 1984
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Automatically generated during migration to IUCLID 6, no data available
IUPAC Name:
Automatically generated during migration to IUCLID 6, no data available
Details on test material:
- Name of test material (as cited in study report): RV 777
- Substance type: Reaction mass of dialuminium tricalcium hexaoxide (CAS No. 12042-78-3, EC No. 234-932-6) and calcium hydrogen phosphonate (CAS No. 21056-98-4, EC No. 244-182-1)
- Analytical purity: 90 %
- Physical state: white solid
- Lot/batch No.: CH. 659 B
- Bulk density: 0.62 g/ml
- Expiration date of the lot/batch: December 22, 1995
- Stability in vehicle: stable for at least 48 hours in polyethylene glycol
- Storage condition of test material: at room temperature, dry in the dark
- Other: stability under storage conditions: stable for 5 years

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: BRL Ltd., Basel Switzerland
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: males 204-220 g, females 164-171 g
- Fasting period before study: no fastig period before substance application
- Housing: individually housed in polycarbonate cages containing purified sawdust as bedding material (Woody SPF, supplied by Broekman Institute, Someren, The Netherlands).
- Diet: standard pelleted laboratory animal diet (Kliba 343 from Klingentalmühle AG, Kaiseraugst, Switzerland) ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days before start of treatment under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature: 21°C
- Humidity: 55%
- Air changes (per hr): 15
- Photoperiod: Lighting was 12 hours artificial flourescent light and 12 hours dark per day.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
TEST SITE
- Shaving: One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
- Area of exposure: approximately 25 cm³ (5x5 cm) for males and 18 cm³ (3,5x5 cm) for females
- Type of wrap if used: application on a gauze patch fixed successively to aluminium foil and flexible bandage (Coban, 3M, St. Paul, USA), with drops of petrolatum


REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed with tissue moistened with tap-water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Preparation: The formulation was prepared immediately prior to dosing. The test substance was weighed into a glass flask on an analytical balance and the vehicle (w/w) was added. Adjustment was made for specific gravity (1.126 g/ml) of vehicle. Homogeneity of the test substance in vehicle was obtained by using a magnetic stirrer, electric blender and a spatula.
- Dose level: 2000 mg/kg body weight
- Dose volume: 10 ml/kg body weight
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations:
-- Mortality/Viability: At periodic intervals on the day of dosing (day 1) and twice daily thereafter for 14 days
-- Body weights: Days 1 (pre-administration), 8 and 15
-- Symptoms: At periodic intervals an the day of dosing (day 1) and once daily thereafter for 14 days. All signs of reaction to treatment were recorded with particular attention paid to changes in the skin (treated skin), fur, eyes and mucous membranes, as well as to behaviour pattern, tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of ill health or behavioural changes were seen during the study.
Body weight:
The females showed lower body weight gain than expected for rats of this age and strain over the 2 weeks of observation.
The body weight gain shown by the males and other females over the study period was considered to be similar to that expected of normal untreate animals of the same age and strain.
Gross pathology:
Macroscopic post mortem examination of the surviving animals did not reveal any abnormalities that were considered to have arisen as an effect of treatment.
Other findings:
- Treated skin abnormalities: Erythema was observed on the skin area of 1 male immediately following bandage removal on day 2.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
According to the criteria for classification and labeling requirements for dangerous substances (EEC Directive 83/467/EEC, Annex VI of the EEC Directive 67/548/EEC), RV 777 does not have to be classified as dangerous substance and has no obligatory labeling requirements.
Executive summary:

In an acute dermal toxicity study according to OECD Guideline No. 402, adopted February 1987 and EEC Directive 84/449/EEC, Part B.3, September 1984, groups of fasted, approximately 8 weeks old male and female Wistar rats were dermally exposed to RV 777 (90 % a.i.) in polyethylene glycol for 24 hours to approximately 25 cm² (males) respectively 18 cm² (females) of body surface area under occlusive conditions at a dose of 2000 mg/kg bw (limit test) and observed for 14 days.

Dermal LD50 Males and Females > 2000 mg/kg bw.

No mortality occured during the study period. No clinical signs of ill health or behavioural changes were seen during the study. Three females showed lower body weight gain than expected for rats of this age and strain over the 2 weeks of observation.

The body weight gain shown by the males and other females over the study period was considered to be similar to that expected of normal untreate animals of the same age and strain. Erythema was observed on the skin area of 1 male immediately following bandage removal on day 2. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities that were considered to have arisen an an effect of treatment.

RV 777 is of low Toxicity based on the dermal LD50 > 2000 mg/kg bw in male and female rats.