Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 25 May to 16 June 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
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: colourless liquid
Details on test material:
- Name of test material (as cited in study report): Propylidynetrimethyl trimethacrylate
- Physical state: colourless liquid
- Storage condition of test material: in a sealed container, at room temperature in the dark

Test animals

Species:
rat
Strain:
other: HsdHan:WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, UK
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: from 279 to 344 g (males) and from 186 to 201 g (females)
- Housing: in groups of up to five during the acclimatisation period. From the day prior to dosing (Day –1), the rats were housed individually.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1 (Special Diets Services Ltd, Witham, UK ), ad libitum
- Water (e.g. ad libitum): mains water, ad libitum
- Acclimation period: 21 to 23 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-65
- Air changes (per hr): 15 to 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25 May 2010 To: 16 June 2010

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsum
- % coverage: 10 % of total body surface
- Type of wrap if used: A dense gauze patch was placed over the treated skin and retained in place by an elasticated, open-weave, adhesive compression bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): . The dermal test site of each rat was lightly brushed clean of any solid residues and swabbed with water-moistened cotton wool.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.82 mL/kg
- Constant concentration used: yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs were recorded immediately post dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Individual records of clinical signs were maintained for each treated rat. Rats were weighed on Day 1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes
- One male and one female were used for preliminary test (results included in the main test)
Statistics:
None

Results and discussion

Preliminary study:
No mortality found.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality found.
Clinical signs:
There were no clinical signs of reaction to treatment. No dermal reactions were noted.
Body weight:
All rats gained weight over of the study period (animal 33M lost -1 g (Days 1 to 8) and animal 38F did not gain weight (Days 1 to 8), see table 2).
Gross pathology:
Red foci on the thymus, red foci on the mandibular lymph nodes and pale kidneys were noted at necropsy of in one male. Large mandibular lymph nodes and pelvic dilatation of the kidneys were noted in one female.
No macroscopic changes were observed at necropsy of all other animals.
Other findings:
No data

Any other information on results incl. tables

Table 2: individual body weights

Dose level (mg/kg)

Animal number and sex

Body weight (g) at:

Increment (g)

Day -1

Day 1

Day 4

Day 8

Day 15

Day 1

to 8

Day 8

to 15

2000

30M

275

279

285

297

317

18

20

31M

322

324

315

326

334

2

8

32M

289

285

285

291

304

6

13

33M

339

341

332

340

351

-1

11

34M

339

344

343

354

371

10

17

2000

35F

201

201

204

206

219

5

13

36F

200

196

197

201

212

5

11

37F

187

189

184

191

195

2

4

38F

194

191

190

191

204

0

13

39F

186

186

185

187

201

1

14

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, propylidynetrimethyl trimethacrylate is not classified according to the criteria of CLP Regulation(EC) N° (1272-2008).
Executive summary:

Propylidynetrimethyl trimethacrylate was tested for acute dermal toxicity in wistar rats in a limit dose assay, according to OECD guideline 402 in compliance with GLP. Groups of rats (5/sex) were administered a single dermal dose of propylidynetrimethyl trimethacrylate at 2000 mg/kg bw on clipped skin using a semi-occlusive patch for 24 h. Examinations for mortality, clinical signs and body weight gain were performed during a 14-day observation period. All surviving animals were necropsied at the end of the observation period. No deaths and clinical signs occurred during the observation period. All rats gained weight over of the study period. Red foci on the thymus, red foci on the mandibular lymph nodes and pale kidneys were noted at necropsy in one male. Large mandibular lymph nodes and pelvic dilatation of the kidneys were noted in one female. No cutaneous reactions were recorded in any animal throughout the observation period. The acute dermal LD50 for males and females was greater than 2000 mg/kg bw. Under the test conditions, propylidynetrimethyl trimethacrylate is not classified according to the criteria of the Annex VI of the Directive 67/548/EEC and the CLP Regulation(EC) N° (1272-2008).