Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 March 2010 - 13 April 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

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
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions
Deviations:
no
GLP compliance:
yes
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): Ebecryl® P116 radiation curing resins- Substance type: Clear colourless liquid- Physical state: liquid- Analytical purity: 99% (wt/wt)- Composition of test material, percentage of components: Tripropylene glycol, esters with acrylic acid, reaction products with diethylamine- Main constituents:65-85% Diadduct TPGDA-DEA29-20% Mono-adduct TPGDA-DEA12-5% TPGDA-AA-DEA22-10% TPGMA-DEA- Lot/batch No.: JBGK0064T- Expiration date of the lot/batch: 29 July 2010- Stability under storage conditions: Stable- Storage condition of test material: At room temperature protected from light- Test substance handling: Use amber-coloured glassware or wrap container in thin -foil- Specific Gravity: 0.99- pH: Neutral- Stability at higher temperatures: Yes, maximum temperature keep not above 40°C

Test animals

Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.- Age at study initiation: Young adult animals (approx. 10 weeks old)- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Woody-Clean type 3/4, Tecnilab-BMI BV, Someren, The Netherlands) and paper as cage-enrichment (Enviro-dri, Tecnilab-BMI BV, Someren, The Netherlands). - Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).- Water (e.g. ad libitum): Free access to tap water.- Acclimation period: The acclimatization period was at least 5 days before the start of treatment under laboratory conditions.- Health inspection: A health inspection was performed prior to treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.ENVIRONMENTAL CONDITIONS- Temperature (°C): 20.0– 21.7ºC- Humidity (%): 41 - 54%- Air changes (per hr): approximately 15 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day. IN-LIFE DATES: From: 30 March 2010 to 13 April 2010

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only. * Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).Frequency: Single dosage, on Day 1.Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw (2.02 mL/kg bw) .Dose volume calculated as dose level (g/kg) / specific gravity.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Dose level (volume): 2000 mg/kg bw (2.02 mL/kg bw). Dose volume calculated as dose level (g/kg) / specific gravity.DOSAGE PREPARATION: The test substance was dosed undiluted as delivered by the sponsor.Duration of observation period following administration: 14 days- Frequency of observations and weighing:Mortality/Viability: Twice dailyBody weights: Days 1 (pre-administration), 8 and 15.Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.- Necropsy of survivors performed: yes- Other examinations performed: none.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Lethargy, tremor, hunched posture, laboured and shallow respiration, piloerection, chromodacryorrhoea, ptosis, and hyperthermia were noted in the majority of animals. Most animals had recovered from the symptoms between Days 4 and 6. General or focal erythema, scabs, scars, scales, fissures, dryness, thickened area, hypersensitivity to touch and necrosis were seen in the treated skin-area of most of the animals during the observation period.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Conclusions:
Under the test conditions, the dermal LD50 of the test substance in Wistar rats was > 2000 mg/kg bw.
Executive summary:

A study was conducted to determine the LD50 of the test substance according to OECD Guideline 402, EC Method B.3, EPA OPPTS 870.1200 and JMAFF Notification No. 8147 .

No mortality was observed at the dose level of 2,000 mg/kg bw in rats after a single dermal application.

Under the test conditions, the dermal LD50 of the test substance in Wistar rats was > 2000 mg/kg bw.