Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From the 29th of March to the 19th of April, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study conducted according to internationally accepted guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Environmental fate/Ecotoxicological/Toxicological studies:
Storage: Room temperature, 20-24 °C, in the dark
Stability: pure, for 5 years; in solvent > 24 hours in water, DMSO, DMF, stable for at least 2 hours in aqueous medium.
Evidence of chemical instability at pH 6: none
Safety precaution: routine hygienic procedures were sufficient to assure personnel health and safety.
Toxicological studies:
Preparation: On the day of the experiment, the test article was suspended in Carboxymethylcellulose (1 %).
The vehicle was chosen to its nontoxicity for the animals. All animals received a single standard dose volume of 10 mL/kg body weight orally.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST SYSTEM
Acclimatization March 29 to April 4, 1990
Observation April 5 to April 19, 1990
Source: BRL, Biological Research Laboratories Ltd, Wolferstrasse 4, CH-4414 Fullinsdorf
Number of animals 5 males per group 5 females
Total number of animals 20 males, 20 females
Age at start of treatment males: 10 weeks, females: 12 weeks
Body weight at start males: 235 — 268 g of treatment females: 203-224 g
Identification: By unique cage number and corresponding color coded spots on the tail.
Randomization: Randomly selected at time of delivery in groups of five.
Acclimatization: One week under laboratory conditions, after veterinary examination.

HUSBANDRY
Room No.: 136
Standard Laboratory Conditions:
Air-conditioned with 10-15 air changes per hour, and hourly monitored environment with temperature 22±3 °C, relative humidity 40-70 %, 12 hours artificial fluorescent light/12 hours dark, music/light period.
Accommodation: groups of five in Nakrolon type-3 cages with standard softwood bedding (‘Lignocel’, Schill AG, CH-4132 Muttenz).
Diet: pelleted standard Kliba 343, Batches 67/90 and 68/90 rat maintenance diet (‘Kliba’, Klingentalmuehle AG, CH-4303 Kaiseraugst) available ad libitum.
Analysis for contaminants performed.
Water: community tap water from Itingen, available ad libitum. Analyses for contaminants performed.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
Twenty-four hours after the application, the dressing was removed. The treated skin was washed with lukewarm tap water, dried with disposable paper towels and the skin reaction was assessed according to the method of Noakes and Sanderson (Noakes, D.N. and Sanderson, D.M. A Method for Determining the Dermal Toxicity of Pesticides. Brit. 3. Industr. Med., 26, 59-U, 1969).
Duration of exposure:
24 hours
Doses:
Application Volume kg body weight: 4 ml at 2000 mg/kg
No. of animals per sex per dose:
5 males per group 5 females
Total number of animals 20 males, 20 females
Control animals:
not required
Details on study design:
Approximately 24 hours before treatment, the backs of the animals were shaved with an electric clipper, exposing an area of approximately 10 % of the total body surface. On test day 1, the test article was applied evenly on the skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.
Observations:
Mortality/Viability: Four times during test day 1, and daily during days 2-15.
Clinical Signs: Each animal had an examination for changes in appearance and behaviour four times during day 1, and daily during days 2-15. All abnormalities were recorded. Due to the 24 hour semi-occ1usive treatment, the starting with day 2 of test.
Body Weights: Test days 1 (pre-admnistration), 8 and 15.
Necropsies were performed by experienced prosectors.
All animals were necropsied.
All animals were killed by intraperitoneal injection of sodium pentobarbitone.
GENERAL BEHAVIOUR NOSE
Aggressiveness, vocalization, restlessness/excitation, nervousness, fear sedation, somnolence, sleep-coma
RESPIRATION
Apnea, dyspnea, rales
EYE
Chromodacryorrhea, exophthal mosmiosis, mydriasis whitish discharge, lid adhesion, negative corneal reflex
NOSE
rhinorrhea, epistaxis
MOTILITY
Akinesia, ataxia, dropped head, hyperkinesia, hypokinesia, paralysis, flaccid, paralysis, spastic, paddling movements, stiff gait, rolling movements
BODY POSITION
Ventral body position, latero-abdominal position, hunched posture
MOTOR SUSCEPTIBILITY
spasms, tonic muscle spasms, clonic muscle spasms, opisthotonus, saltatory spasms, trismus, tremor, muscie—twitching, muscle-twitching,
generalized
SKIN
Erythema, edema, necrosis, crusts, scale formations
VARIOUS
Loss of weight, emaciation, diarrhea, ruffled fur, necrosis on appilication AREA, salivation, pallor, cyanosis

Statistics:
The LOGIT Model could not be applied to the observed rate of death. The toxicity was estimated without use of a statistical model.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No death occurred at 2000 mg/kg bw
Mortality:
0 % at 2000 mg/kg
Clinical signs:
at 2000 mg/kg males/females skin/fur: general erythema (back), scales (back), skin yellow (back). All animals had recovered until termination of the study. Discoloration was observed until termination of test.
No systemic symptoms were observed in the animals throughout the study.
Body weight:
not affected by the test article treatment throughout the entire study.
Gross pathology:
at 2000 mg/kg males/females sacrificed : no macroscopical findings noted.

Applicant's summary and conclusion

Interpretation of results:
not classified
Conclusions:
LD50 dermal >2000 mg/kg bw.
Executive summary:

Materials and methods

The test article was applied to the skin of rats of both sexes for 24 hours at a single dose of 2000 mg/kg.

Observations

The following death rate was observed: 0 % at 2000 mg/kg. Based on these observations, the LOGIT-Model could not be applied to the observed rate of death.

The following local signs were observed: at 2000 mg/kg males/females skin/fur: general erythema (back), scales (back), skin yellow (back).

All animals had recovered until termination of the study. Discoloration was observed until termination of test. No systemic symptoms were observed in the animals throughout the study. The body weight gain of the animals was not affected by the test article treatment throughout the entire study.

The following macroscopical organ findings were observed: at 2000 mg/kg males/females sacrificed : no macroscopical findings noted.

Results

LD50 dermal >2000 mg/kg bw.