Reaction products of 2-(chloromethyl)oxirane and glycerol

Acute Toxicity: dermal

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of 2-(chloromethyl)oxirane and glycerol

EC Number:

701-197-2

Molecular formula:

6 individual glycidether components (Molecular range ca. 200 - 600 g/mol)

IUPAC Name:

Reaction products of 2-(chloromethyl)oxirane and glycerol

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 or test system 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:

other: No clinical signs and no cutaneous reactions were observed during the study

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:

other: EU GHS criteria not met

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.