Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted Feb. 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted May 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted August 1998
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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: 225 - 251g; females: 203 - 219g
- Fasting period before study: no
- Housing: single housing in Makrolon type III cages
- Diet (e.g. ad libitum): VRF1(P); SDS Sepcial Diets Services, Altrip, Germany
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
olive oil
Remarks:
only for the 500mg/kg b.w. group; 2000mg/kg were applied undiluted
Details on dermal exposure:
TEST SITE
- Area of exposure: app. 40cm² (= at least 10% of body surface)
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.71ml/kg b.w. (2000mg/kg); 2.00ml/kg b.w. (500mg/kg)
- Concentration (if solution): undiluted (2000mg/kg); 25g/100mL (500mg/kg)

Duration of exposure:
24h
Doses:
500 mg/kg bw, 2000 mg/kg bw
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 application, daily thereafter on workdays
- Frequency of weighing: on day 0, weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, skin findings (scored according to Draize 30-60minutes after removal of the dressing and weekly thereafter)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
Systemic effects: none

Local effects in males:
2000 mg/kg: erythema grade 2 on day 1, which decreased to grade 1 on day 2 or 3
500 mg/kg: erythema grade 3 on day 1 in 3 of 5 males which decreased to grade 1 until day 5. Grade 1 or 2 erythema were noted in the other 2 males on days 1 and 2.
All local effects were reversible within 7 days at the latest.

Local effects in females:
2000 mg/kg: erythema grade 3 in 3 of 5 females on day 1 which persisted in two animals until day 6 or 7. Very slight erythema were still noticed on day 10 or day 13 in these animals. Erythema grade 2 which persisted until day 2 or 7 were noted in the remaining 2 females. Incrustations were noted in 4 animals from day 2/3 to day 14.
500 mg/kg: erythema grade 3 on days 1 and 2, which decreased to grade 1 until day 5 or 6.
Body weight:
The mean body weight of the animals increased within the normal range throughout the study period.
Gross pathology:
no abnormalities observed

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the median lethal dose (LD50) of the test substance 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), 5 male and 5 female young adult Wistar rats per group were dermally exposed to test groups of 2000 and 500 mg/kg bw of 1,4-butanediylbis[oxy(2-hydroxy-3,1-propanediyl)] diacrylate (undiluted or preparation in olive oil) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semiocclusive dressing for 24 hours. During the 14 day observation period, no mortality occured and no signs for systemic toxicity were recorded. Slight to moderate erythema (grade 1 to 3) were noted, and incrustations occured in females exposed to 2000 mg/kg bw. The mean body weight of the animals increased within the normal range throughout the study period. No macroscopic pathologic abnormalities were noted. Accordingly, the acute dermal median lethal dose (LD50) was determined to be higher than 2000 mg/kg bw.