Registration Dossier

Administrative data

Description of key information

Both oral and dermal acute toxicity studies were available on TMPTMA. Oral and dermal LD50 are higher than 2000 mg/kg bw in rats. 
An acute toxicity study is available by intraperitoneal route: the ip LD50 for propylidynetrimethyl trimethacrylate is 3900 mg/kg bw in male and female rats.
No study is available by inhalation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 05 May to 11 June 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: HsdHan:WIST
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, UK
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: from 195 to 229 g
- Fasting period before study: overnight prior to dosing until 3 h after dosing
- Housing: in groups of up to five during the acclimatisation period. From the day prior to dosing (Day –1), the rats were housed in groups of three.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1 (Special Diets Services Ltd, Witham, UK ), ad libitum except during fasting period
- 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: 11 June 2010
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Volume applied: 1.82 mL/kg
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
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. Rats were weighed on Day 1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
None
Preliminary study:
No data
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No clinical signs were seen.
Body weight:
All rats gained weight during the first and second weeks of the observation period.
Gross pathology:
Red foci on the thymus, a large mandibular lymph node and red foci on the mandibular lymph node were noted at necropsy on one animal.
No abnormalities were noted at necropsy of all other animals.
Other findings:
No data

Table 1: Individual body weights and weekly increments

Dose level (mg/kg bw)

Animal number

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

40

195

183

189

204

208

21

4

41

229

217

220

244

257

27

13

42

208

195

200

218

229

23

11

2000

43

209

201

209

215

225

14

10

44

214

200

211

217

232

17

15

45

216

208

217

221

236

13

15

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 for propylidynetrimethyl trimethacrylate is higher than 2000 mg/kg bw in rats.
Executive summary:

In an acute oral class method toxicity study performed in accordance with GLP and OECD guideline 423, 6 Sprague Dawley female rats were given a single oral dose of propylidynetrimethyl trimethacrylate at the limit test dose of 2000 mg/kg bw.

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. Rats were weighed on Day 1 (day before dosing) and on Days 1, 4, 8 and 15.

No mortality, no clinical signs, no change in body weight and no abnormalities in macroscopic examination of main organs were observed except red foci on the thymus, a large mandibular lymph node and red foci on the mandibular lymph node in one animal.

The oral LD50 for propylidynetrimethyl trimethacrylate is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation(EC) N° (1272-2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The oral acute study is considered to be reliable, and was performed according to the OECD guidelines.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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
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
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
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
Preliminary study:
No mortality found.
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

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

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).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The dermal acute study is considered to be reliable, and was performed according to the OECD guidelines.

Additional information

Oral acute toxicity study (Dreher 2010):

In an acute oral class method toxicity study performed in accordance with GLP and OECD guideline 423, 6 Sprague Dawley female rats were given a single oral dose of propylidynetrimethyl trimethacrylate at the limit test dose of 2000 mg/kg bw.

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. Rats were weighed on Day 1 (day before dosing) and on Days 1, 4, 8 and 15.

No mortality, no clinical signs, no change in body weight and no abnormalities in macroscopic examination of main organs were observed except red foci on the thymus, a large mandibular lymph node and red foci on the mandibular lymph node in one animal.

The oral LD50 for propylidynetrimethyl trimethacrylate is higher than 2000 mg/kg bw in rats.

 

Dermal acute toxicity study (Dreher 2010):

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.

Intraperitoneal acute toxicity study (Auletta 1982):

The purpose of this study was to evaluate the acute toxicity of the test material when administered by intraperitoneal injection to rats ; to determine the intraperitoneal LD50 of the material; and to determine whether neurologic effects could be produced with acute administration.

Five male five female rats were given a single oral dose of propylidynetrimethyl trimethacrylate at the dose of 2000, 3500, 5000 and 8000 mg/kg bw.

No animal died at 2000 mg/kg, however 4 males died at 3500 mg/kg, 4 males and 5 females at 5000 mg/kg, and 5 males and 4 females at 8000 mg/kg. Animals at all dose levels exhibited a number of neurologic abnormalities. Signs seen in animals which survived as well as those which included tremors, convulsions, ataxia, apparent hallucinations, head-searching behavior, alterations in limb and body tone (flaccidity or rigidity)., pelvic elevation, and impaired pupillary, righting, visual placing, toe pinch and startle reflexes. Signs seen only in animals which died (generally in single animals) included circling, pranding, spasticity, compulsive biting and impaired corneal reflex. Soft stool and fecal staining occurred in both corn oil and test material-treated animals and was, not considered related to test material administration. Signs seen in several test material treated animals during the post-dose period included decreased activity, hyperpnea, food consumption decrease, unthrifty coat and a number of other abnormalities. Animals which died and those which were killed after 14 days exhibited a large number of postmortem abnormalities, most notably in the abdominal viscera. Most of these appeared to represent irritation and/or infectious sequelae resulting from intraperitoneal injection of the vehicle and/or test material.

To conclude, the ip LD50 for propylidynetrimethyl trimethacrylate is 3900 mg/kg bw in male and female rats.

Justification for classification or non-classification

As oral and dermal LD50 are higher than 2000 mg/kg bw in rats, propylidynetrimethyl trimethacrylate is not classified in acute toxicity according to the CLP Regulation (EC) N°1272/2008.