Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Mar. 3, 1988 to May 5, 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented, according to accepted guideline, with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Tif: RAI f (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Ltd. Animal Production 4332 Stein / Switzerland.
- Age at study initiation: 7 to 8 weeks.
- Weight at study initiation: 220 to 248 g.
- Housing: The rats, segregated by sex, were individually housed in Macrolon cages type 3, with standardized soft wood bedding (Societe Parisienne des Sciures, Pantin).
- Diet (e.g. ad libitum): ad libitum.
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: At least 5 days before application.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C.
- Humidity (%): 55 ± 10%.
- Air changes (per hr): Approximately 15 air changes per h.
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
peanut oil
Details on dermal exposure:
TEST SITE
- Area of exposure: Back of the rat.
- % coverage: At least 10% of the body surface.
- Type of wrap if used: was covered with a gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Lukewarm water.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL/kg body weight.
- Concentration (if solution): 2000 mg/kg body weight.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg body weight.
No. of animals per sex per dose:
5 per sex.
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
Mortality: Daily; a.m. and p.m. on working days, a.m. on weekend days.
Signs and symptoms: Daily.
Body weight: At start and on Days 7 and 14.
Necropsies: The animals were submitted to a gross necropsy at the end of the observation period.
- Necropsy of survivors performed: Yes.
Statistics:
From the body weights, the group means and their standard deviations were calculated.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality.
Clinical signs:
Ruffled fur, dyspnea, and abnormal body positions were seen, being common symptoms in acute tests. Additionally, reduced spontaneous activity was observed during the application day and Day 1 after application. The animals recovered within 10 days. Refer to Table 1.
Body weight:
Refer to Table 2.
Gross pathology:
No deviations from normal morphology were found.
Other findings:
Not available.

Any other information on results incl. tables

Table 1 Signs and symptons

observations

Exposure day: hours

Days of post-exposure period

 

1

2

3

5

1

2

3

4

5

6

7

8

9

10

11

12

13

>13

2000 mg/kg males

ruffled fur

X

X

X

X

X

X

X

X

X

X

X

X

X

 

 

 

 

 

dyspoea

X

X

X

X

X

X

X

X

X

X

 

 

 

 

 

 

 

 

hunched post.

 

 

 

 

X

X

X

X

 

 

 

 

 

 

 

 

 

 

ventr.recumb.

X

X

X

X

X

 

 

 

 

 

 

 

 

 

 

 

 

 

red.spot.act.

X

X

X

X

X

 

 

 

 

 

 

 

 

 

 

 

 

 

2000 mg/kg females

ruffled fur

X

X

X

X

X

X

X

X

X

X

X

X

X

 

 

 

 

 

dyspoea

X

X

X

X

X

X

X

X

X

X

 

 

 

 

 

 

 

 

hunched post.

 

 

 

 

X

X

X

X

 

 

 

 

 

 

 

 

 

 

ventr.recumb.

X

X

X

X

X

 

 

 

 

 

 

 

 

 

 

 

 

 

red.spot.act.

X

X

X

X

X

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2 Mean body weight and standard deviation

 

Males

Females

Dose (mg/kg)

Day 1

Day 7

Day 14

Day 1

Day 7

Day 14

2000

240/ 9.4

278/16.3

310/23.2

233/ 7.7

246/10.0

256/ 7.8

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Single dermal administration of the test substance (OECD guideline 402) to rats did neither induce mortalities nor adverse effects. LD50 is considered to be > 2000 mg/kg bw.