Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 19, 1992 - June 16, 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987-02-24)
Deviations:
yes
Remarks:
(test conducted with 1600 mg/kg bw, the max. technically achievable concentration)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Solid, white
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
other: Tif: RAI f1 (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: Young adult rats
- Weight at study initiation: 225 - 289 g
- Housing: Individual housing in Macrolon cages type 3 with standardised soft wood bedding (Societe Parisienne des Sciures, Pantin, France)
- Diet: ad libitum NAFAG 890 Tox, NAFAG, Gossau/ SG, Switzerland
- Water: ad libitum
- Acclimation period: At least 5 days

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

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: 0.5 % (w/v) Carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80
Details on dermal exposure:
TEST SITE
- Area of exposure: Back of the rat
- % coverage: ≥ 10
- Type of wrap: Gauze-lined semi-occlusive dressing fastened around the trunk with an adhesive elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washing the skin with lukewarm water
- Time after start of exposure: 24 h

VEHICLE
- Amount(s) applied: 4 ml/kg bw
- Concentration: 40 %

OTHER
24 h before study begin an area of the back of the rat was shaved with an electric clipper (at least 10 % of the body surface)
Duration of exposure:
24 h
Doses:
1600 mg/kg bw
Due to the physical-chemical properties, the test substance had to be suspended in a higher vehicle volume (40 instead of 50%). Adhering to guidelines and SOP, and respecting the maximal application volume (4 ml/kg) a limit dose of 1600 mg/kg has been appplied by direct weighing.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: Immediately before study begin and on days 7 and 14
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs and symptoms (daily for 14 days), mortality (daily: a.m and p.m on working days, a.m. on weekend days)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 600 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred in this study.
Clinical signs:
In males and females on application day and the following day slight piloerection was seen. The animals recovered within 2 days.
Body weight:
Normal body weight gain in male animals. Reduced body weight gain in female rats (mean bodyweight at day 1: 237 g, at day 7: 244 g, at day 14: 256 g)
Gross pathology:
No deviations from normal pathology were found.

Any other information on results incl. tables

Table 1: Body weight in male and female animals after day 0, 7 and 14

Body weight [g]

 

 

Males (dose = 1600 mg/kg bw)

 

animal ID

day 0

day 7

day 14

1

270

306

355

2

259

280

296

3

289

303

345

4

271

292

316

5

276

304

329

mean

273

297

328.2

SD

10.9

11

23.4

Females (dose = 1600 mg/kg bw)

 

  animal ID

day 0

day 7

day 14

1

226

231

236

2

225

232

237

3

238

237

263

4

260

265

277

5

235

257

267

mean

236.8

244.4

256

SD

14.1

15.6

18.5

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Upon an acute dermal administration and a 14 day post-treatment observation period, the LD50 was determined to be > 1600 mg/kg body weight.
Executive summary:

The acute dermal toxicity of the test substance was assessed in a toxicity study following OECD guideline 402 and in compliance with GLP. The test article was administered to five rats of each sex by dermal application at 1600 mg/kg body weight for 24 hours. Higher doses were technically not possible. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortality occurred. Piloerection was seen, being a common symptom in acute dermal tests. The animals recovered within 2 days. At autopsy, no deviations from normal morphology were found. The dermal LD50 value of the test substance in rats was established to exceed 1600 mg/kg body weight.