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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well documented 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)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material: 1,2,3-Propanetriol, glycidyl ethers
- Substance type: organic
- Physical state: liquid
- Storage condition of test material: at room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS - Sprqgue-Dawley ICO:OFA-SD (IOPS Caw)
- reason for this choice: rodent species are generally accepted by regulatory authorities for this type of study
- Source: Iffa Credo, L'Arbresle, France
- Age at study initiation: on the day of treatment, the animals were approximately 8 weeks old
- Weight at study initiation: mean body weight */- standard deviation of 267 +/- 6 g forthe males and 233 +/- 8 g for females.
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum): All tha animals had free access to A04C pelleted diet. Each batch of food was analysed by the supplier for composition and contaminant levels.
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
Bacteriological and chemical analyses of the water and diet, including the detection of possible contaminants pesticides, heavy metals and nitrosamines, are performed regularly by external laboratories.
No contaminants are known to be present in the diet, drinking water or bedding material at levels which may be expected to interfere with or prejudice the outcome of the study
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2 °C
- Humidity (%):30 - 70 %
- Air changes (per hr): 12 cycles / hours of filtered, non-recylced air
- Photoperiod (hrs dark / hrs light): 12 h / 12 h
The temperature and relative humidity were under continuous control and recording. The records were checked daily and retained. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment are verified and calibrated at regular intervals. Duringthe acclimatization period, four to seven animals of the same sex were housed in polycarbonate cages (48 cm * 27 cm * 20 cm). During the treatment period, the animals were housed individually in polycarbonate cages (35,5 cm * 23.5 cm * 19.3 cm). Each acge contained dust-free sawdust. Bacteriological and chemical analyses ofthe sawdust, including the detection of possible contaminants (pesticides, heavy metals) are performed regularly by external laboratories.

Identification: the animals were identified individually by earmarks or earnotches

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure:
- % coverage:
- Type of wrap if used:

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Constant volume or concentration used: yes/no
- For solids, paste formed: yes/no
Duration of exposure:
single 24 hour exposure
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males / 5 females
Control animals:
yes, concurrent no treatment
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Thereafter, observations 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.
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 of survivors performed: yes
On day 15, all animals were killed by carbon dioxide asphyxiation and a macroscopic examination was performed. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities was performed. In case of macroscopic lesions, organ samples were taken and preserved in 10% buffered formalin. No microscopic examination was performed.
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: No mortality occurred
Mortality:
No death occurred during the study
Clinical signs:
No clinical signs and no cutaneous reactions were observed during the study
Body weight:
One female did not gain weight during the first week of the study and another female lost weight during the second week of the study. The body weight gain of the other animals was not affected by treatment with the test substance.
Gross pathology:
Macroscopic examinations of the main organs of the animals revealed no apparent abnormalities.

Any other information on results incl. tables

Table 1: Individual clinical signs and mortality
Dose Time Animals Mortality Clinical signs
(mg/kg) Males Females
2000 30 min 01-02-03-04-05 01-02-03-04-05 No None
lh-2h-5h 
D 2 to D 15.
min:minutes
h  :hour
Table2:Cutaneous reactions
Dose Time Animals Cutaneous reactions
mg/kg Males Females
2000 D 2 to D15 01-02-03-04-05 01-02-03-04-05 None
D: day

Table 3: Individual and mean body weight and weekly body weight change of treated rats (g)
Dose Volume Sex Animals Days
mg/kg ml/kg 1 (1) 8 (8) 15
2000 1.67 Male 01 270 37 307 35 342
02 261 62 323 45 368
03 264 29 293 39 332
04 264 26 290 44 334
05 277 32 309 35 344
M 267 37 304 40 344
SD 6 14 13 5 14
2000 1.67 Female 01 239 0 239 25 264
02 221 26 247 23 270
03 241 31 272 -19 253
04 230 25 255 21 276
05 235 14 249 19 268
M 233 19 252 14 266
SD 8 12 12 I8 9
(1)  - Body weight gain
M   - Mean
SD  - Standard Deviation

Table 4: Individual macroscopic examinations at necropsy
Dose Time Animals Macroscopic abnormalities
mg/kg  Males Females
2000 D15 01-02-03-04-05 01-02-03-04-05 None
D: day

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions tests, the dermal LD50 ofthe test substance is higher than 2000 mg/kg in rats.
Executive summary:

The test substance (targert substance GE-100) was applied to the skin of one group of ten Sprague-Dawles rats( five males and five females). The application was performed with the undiluted test substance at the dose of 2000 mg/kg, taking into consideration that its specific gravity was 1.2 . 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 ofthe test substance. No death occurred at 2000 mg/kg. No clinical signs were observed during the study. One female did not gained weight during the first week of the study and another female lost weight during the second week of the study. The body weight gain of the other animals was not affected by treatment with the test substance. No cutaneous reactions were observed. No apparent abnormalities were observed at necropsy. In conclusion, under the experimental conditions, the dermal LD50 of the test substance is higher than 2000 mg/kg in rats.