Propylidynetrimethyl trimethacrylate

Endpoint summary

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 but this route of exposure does not need to be further investigated in accordance with Annex VIII of REACH.

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

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17 December 2001

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 or test system 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:

other: No clinical signs were seen.

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 CLP Regulation (EC) N° 1272-2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

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

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 24 February 1987

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 or test system 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:

other: There were no clinical signs of reaction to treatment. No dermal reactions were noted.

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 CLP Regulation (EC) N° 1272-2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

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

acute toxicity: oral (Covance 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.

acute toxicity: inhalation:
According to the Regulation EC no.1907/2006 : "In addition to the oral route, for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. If there is only one route of exposure, information for only that route need be provided".
Acute data are available by oral and dermal route on TMPTMA.
Moreover the test substance has low vapour pressure (about 0.00345 Pa at 20°C) and high boiling point (>160 °C), so the potential for the generation of inhalable forms is low and exposure to humans via the inhalatory route would only be via aerosols and would be quite limited.
Therefore no acute inhalation test needs to be performed.

acute toxicity: dermal (Covance 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.

acute toxicity: ip (Bio/dynamics 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.