Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-06-10 to 1998-06-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

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:
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): POLYRAM SL
- Physical state: pale yellow translucent liquid
- Analytical purity: 100 % (expressed in complex substance)
- Purity test date: not stated
- Lot/batch No.: 6108
- Expiration date of the lot/batch: 1999 /03
- storage conditions : at room temperature; protected from light

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: IFFA CREDO ( 69210 L'ARBRESLE, FRANCE)
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 264 +/- 5g for the males and 226 +/- 4g for the females
- Fasting period before study: not applicable
- Housing: individually in polycarbonate cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2°C
- Humidity (%): 30 to 70 %
- Air changes (per hr): approximately 12 cycles/hour of filtered, non recycled air
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area
- % coverage: approximately 10%
- Type of wrap : hydrophilic gauze pad, hypoallergenic aerated semi-occlusive dressing and a restraining bandage
No residual test substance was observed at removal of the dressing.

The single administration was performed on 10 June 1998 in the morning (day 1) and was followed by a 14-day observation period (day 15).

TEST MATERIAL
- Amount applied : 2000mg/kg bw undiluted taking into consideration that the specific of the test substance was 0.92.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
One group of ten animals (five males and five females)
Control animals:
not required
Details on study design:
- Clinical signs and mortality :
The animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until day 15. Type, time of onset and duration of clinical signs were recorded for each animal individually. Time of death was recorded individually, in terms of the number of hours or days after dosing.

- Body weight :
The animals were weighed individually just before administration of the test substance on day 1 and then on days 8 and 15.
The body weight gain of the treated animals was compared to that of CIT control animals with the same initial body weight.

- Necropsy :
On day 15, all animals were killed by carbon dioxide asphyxiation and a macroscopic examination was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Mortality:
No deaths occured during the study.
Clinical signs:
No clinical signs were observed during the study.
A well-defined erythema was observed in all animals on day 2 ; it persisted up to the end of the observation period (day 15) in 3/5 females.
Crusts were noted on the treatment site in all animals from day 3 up to the end of the observation period (day 15).
Necrosis was observed in two animals (one female and one male) between days 4 and 7.
Dryness of the skin was also noted in two animals (two males) on days 14 and 15 (See tables 1 and 2 in results and discussion free-text for details).
Body weight:
The body weight gain of 1/5 males and 2/5 females was reduced between days 1 and 8 ; it returned to normal thereafter. The body weight gain of the other animals was not affected by treatment with the test substance (See tables 3 and 4 in results and discussion free-text for details).
Gross pathology:
Macroscopic examination of the main internal organs of all the animals revealed no apparent abnormalities.

Any other information on results incl. tables

Table 1: Cutaneous reactions in male rats

 Animal/Time Day 2  Day 3 Day 4 -7  Day 8 -9  Day 10 -13   Day 14 -15
 1  Erythema  Erythema  Erythema, crusts  Erythema, crusts  Crusts  Crusts
 2  Erythema   Erythema  Erythema, crusts Erythema, crusts   Erythema, crusts  Crusts
 3  Erythema  Erythema  Erythema, crusts  Erythema, crusts  Crusts  Dryness of skin
 4  Erythema  Erythema  Necrosis, crusts  Erythema, crusts  Crusts  Dryness of skin
 5  Erythema  Erythema  Erythema, crusts  Erythema, crusts  Crusts  Crusts

Table 2: Cutaneous reactions in female rats

 Animal/Time Day 2  Day 3 Day 4 -7  Day 8 -9  Day 10 -13   Day 14 -15
 1  Erythema  Erythema  Necrosis, crusts  Erythema, crusts  Crusts  Crusts
 2  Erythema   Erythema  Erythema, crusts Erythema, crusts   Erythema, crusts  Erythema, crusts
 3  Erythema  Erythema  Erythema, crusts  Erythema, crusts  Crusts  Crusts
 4  Erythema  Erythema  Erythema, crusts  Erythema, crusts  Erythema, crusts  Erythema, crusts
 5  Erythema  Erythema  Erythema, crusts  Erythema, crusts  Erythema, crusts  Erythema, crusts

Table 3: Male rats -individual and mean body weight and weekly body weight change (g)

 Animal Day 1   Change Day 1 -8 Day 8   Change Day 8 -15 Day 15 
261 26  287 53 340
2 263 3 266 50 316
3 267 35 302 56 358 
4 271 25 296 57 353
5 258 30 288 46 334
Mean 264 24 288 52 340
S.D. 5 12 14 5 17
Control (n=45) 269 46 (S.D.= 11) 315  47 (S.D.= 11) 361 

Table 4: Female rats -individual and mean body weight and weekly body weight change (g)

 Animal Day 1   Change Day 1 -8 Day 8   Change Day 8 -15 Day 15 
223 11 234 7 241
2 225  3 228 40 268
3 234 15 249 17 266
4 224 1 225 24 249
5 225 11 236 17 253
Mean 226 8 234 21 255
S.D. 4 6 9 12 11
Control (n=45) 228 19 (S.D.=12) 247 13 (S.D.= 7) 260 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (Reg. 1272/2008/EC) and Directive 67/548/EEC
Conclusions:
under these experimental conditions, the dermal LD0 of the test substance is equal to or higher than 2000 mg/kg bw in rats.
Executive summary:

The acute dermal toxicity of the test item was evaluated in rats according to OECD guideline 402 and EU method B.3. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. 

 

As the test substance was anticipated to be non-toxic at 2000 mg/kg bw, a limit test was performed by application of 2000 mg/kg bw of the test substance to one group of five male and five female Sprague-Dawley rats. The undiluted test substance was applied to the skin and the test site was then covered by a semi-occlusive dressing for 24 hours. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test substance. All animals were subjected to necropsy. No mortality and no clinical signs were observed during the study period. The body weight gain was reduced in 1 male and 2 females between days 1 and 8 but returned to normal thereafter. Skin erythema was observed in all rats on day 2 and persisted up to the end of the observation period in 3 out of 5 females. Crusts were also observed in all animals from day 3 up to the end of the study. Necrosis was observed in 1 male and 1 female between day 4 and 7 and dryness of skin was observed in 2 males on days 14 and 15. At necropsy, no apparent abnormalities were detected. The dermal LD0 of the test substance was equal or higher than 2000 mg/kg bw in rats.