(5-ethyl-1,3-dioxan-5-yl)methyl acrylate

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: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted Feb. 1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted May 2008

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

adopted August 1998

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan no. 8147

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(5-ethyl-1,3-dioxan-5-yl)methyl acrylate

EC Number:

266-380-7

EC Name:

(5-ethyl-1,3-dioxan-5-yl)methyl acrylate

Cas Number:

66492-51-1

Molecular formula:

C10H16O4

IUPAC Name:

(5-ethyl-1,3-dioxan-5-yl)methyl acrylate

Details on test material:

- Name of test material (as cited in study report): Laromer LR 8887
- Physical state: clear, yellowish liquid
- Analytical purity: 78.1 g/100 g by H-NMR spectroscopy
- Purity test date: 2011-11-03
- Lot/batch No.: 110009P040
- Expiration date of the lot/batch: no data
- Stability under test conditions: guaranteed by sponsor
- Storage condition of test material: room temperature in the dark
- Other: density as determined by Bioassay: 1.098 g/ml

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: males: app. 8 weeks, females: app. 12 weeks
- Weight at study initiation: males 228 - 237g, females: 209-211g
- Fasting period before study: no
- Housing: single in makrolon cages, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany ad lib.
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 - 70%
- 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: app. 40cm²
- Type of wrap if used: semi-occlusive

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.82ml/kg b.w.

Duration of exposure:

24h

Doses:

2000mg/kg

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 observations: several times on the day of exposure, at least once daily on each workday thereafter
- Frequency of weighing: shortly before administration, weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, scoring of skin findings (30-60min after exposure, several times thereafter)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality occured

Clinical signs:

other: no systemic clinical signs were observed. For local irritation, see table 1 (males) and table 2 (females)

Gross pathology:

no abnormalities noted

Any other information on results incl. tables

Table 1:

Nature and duration of local clinical signs(males)
Dose (mg/kg bw):	2000
Sex:	male
Administration:	1
No. of animals:	5
Animal No.:	R 954	R 955	R 956	R 957	R 958
Abnormalities:
Erythema grade 1:	d9 - d12	d7 - d9	d13	d6 - d9	d8 - d9
Erythema grade 2:	d1 - d2; d7 - d8	d1 - d2; d6	d1 - d2; d9 - d12	d1 - d5	d1 - d2; d7
Erythema grade 3:	d5 - d6	d5	d5 - d8	-	d5 - d6
Edema grade 1:	-	d1 - d2	d1 - d2	d1 - d2	d1 - d2
Incrustations:	d5 - d8	d5 - d6	d5 - d12	-	d5 - d8
Scaling:	d5 - d 13	d5 - d7; d9	d5 - d14	d5 - d8	d5 - d9
Sever scaling:	-	d8	-	-	-
Skin findings beyond the application area:	-	-	d6 - d13	-	-
Significant scratching behavior	d2 - d6	d2 - d5	d2 - d6	d2 - d5	d2 - d6

d: day

Table 2:

Nature and duration of local clinical signs(females)
Dose (mg/kg bw):	2000
Sex:	female
Administration:	1
No. of animals:	5
Animal No.:	R 959	R 960	R 961	R 962	R 963
Abnormalities:
Erythema grade 1:	d12 - d13	d14	d12 - d13	d12 - d13	d14
Erythema grade 2:	d1 - d2; d8 - d9	d1 - d2; d12 - d13	d1 - d2; d7 - d9	d1 - d2	d1 - d2; d12 - d13
Erythema grade 3:	d5 - d7	d5 - d9	d5 - d6	d5 - d9	d5 - d9
Edema grade 1:	d6 - d9	-	-	d6	-
Edema grade 2:	-	-	-	d5	-
Incrustations:	d5 - d12	d5 - d14	d5 - d12	d5 - d14	d5 - d14
Scaling:	d5 - d14	d5 - d14	d5 - d9	d5 - d14	d5 - d14
Skin findings beyond the application area:	-	d6 - d14	d6 - d9	d6 - d14	d6 - d14
Significant scratching behavior	d1 - d5	d1 - d5	d2	d2 - d3	d1 - d5

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of the test material after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of undiluted test item to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. The following test item-related local effects were recorded during the course of the study:

· No mortality occurred

· No signs of systemic toxicity were observed in the animals

· Slight to moderate erythema (grade 1 to 3)

· Slight to well-defined edema (grade 1 to 2)

· Incrustations

· Scaling

· Severe scaling

· Skin findings beyond the application area

· Significant scratching behavior

· The mean body weight of the animals increased within the normal range throughout the study period

· No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.