Propylidynetrimethanol, ethoxylated, esters with acrylic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 July 1998 to 9 September 1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD guideline 401 with minor deviation: the certificate of analysis and purity of the test substance are missing.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

No certificate of analysis

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

yes

Remarks:

No certificate of analysis

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Propylidynetrimethanol, ethoxylated, esters with acrylic acid

EC Number:

500-066-5

EC Name:

Propylidynetrimethanol, ethoxylated, esters with acrylic acid

Cas Number:

28961-43-5

Molecular formula:

n.a.

IUPAC Name:

Poly(oxy-1,2-ethanediyl),.alpha.-hydro-.omega.-[(1-oxo-2- propenyl)oxy]-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1)

Details on test material:

- Substance type: liquid
- Physical state: liquid
- Analytical purity: not advised
- Lot/batch No.: EE 665
- Expiration date of the lot/batch: not advised but assumed to be 6 months from the date of receipt
- Storage condition of test material: 4°C in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan U.K. Ltd, Oxon, England
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 85-97 g
- Fasting period before study: overnight before dosing and for 4 h after dosing
- Housing: in groups of 5 of the same sex
- Diet (e.g. ad libitum): Special Diet Services RMI(E) SQC expanded pellet, ad libitum (except in fasting period)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 18
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21 July 1998 To: 9 September 1998

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.944 mL/kg bw

Doses:

Preliminary experiment: 3200 mg/kg bw
Main study: 2000 mg/kg bw

No. of animals per sex per dose:

Preliminary experiment: 1
Main study: 5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: at least twice daily for mortality. At frequent intervals for clinical signs the day after dosing and twice daily thereafter. Body weights were recorded on day 1 (just before dosing) and day 8 for the preliminary experiment and on days 1, 8 and 15 for the main study.
- Necropsy of survivors performed: yes (macroscopic examination)

Statistics:

None

Results and discussion

Preliminary study:

At 3200 mg/kg bw, the male rat died within 22 h of dosing. Clinical signs prior to death and in the surviving rat comprised piloerection, hunched posture, walking on toes, abnormal faeces, ungroomed appearance and increased salivation in both animals. In addition, pallid extremities was seen in the female only. There were no other signs of reaction and, with the exception of piloerection, recovery was complete in the female by Day 7. Macroscopic examination of the decedent animal revealed congestive changes (characterised by dark appearance/prominent blood vessels) in the subcutaneous tissue, brain, heart, liver and spleen. Congestion with gaseous distension and fluid contents were also noted in the stomach and along the alimentary tract. No macroscopic abnormalities were noted in the remaining animal at the terminal necropsy on Day 8.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths

Clinical signs:

other: Piloerection was observed in all rats within five minutes of dosing. This sign persisted and was accompanied in rats later on Day 1 and/or at later intervals during the study by: hunched posture, waddling/unsteady gait, lethargy, pallid extremities, walki

Gross pathology:

No macroscopic abnormalities were observed for animals killed at study termination on Day 15.

Other findings:

No data

Any other information on results incl. tables

Table 1: Individual and group mean bodyweights (g)

Phase of study	Dose (mg/kg)	Animal No. & Sex	Bodyweight (g) at
			Day 1	Day 8	Day 15	Death
Preliminary	3200	1 M	96	-	-	84
		2 F	99	140	-	-
Main	2000	11M	87	142	197	-
		12 M	93	143	188	-
		13 M	91	146	193	-
		14 M	92	146	194	-
		15 M	85	135	175	-
		Mean	90	142	189	-
		16 F	97	146	171	-
		17 F	96	147	176	-
		18 F	90	126	151	-
		19 F	89	132	158	-
		20 F	93	136	165	-
		Mean	93	137	164	-

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

The oral LD50 for TMPeoTA is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI to the Directive 67/548/CEE and the CLP Regulation (1272/2008).

Executive summary:

In an acute oral toxicity study performed in accordance with GLP and OECD guideline 401, groups of Sprague Dawley rats (5/sex) were given a single oral dose of TMPeoTA undiluted at 2000 mg/kg bw. In a preliminary study, one male and one female received a single oral dose of TMPeoTA undiluted at 3200 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 8 days in the preliminary experiment and for 15 days in the main study. They were all macroscopically necropsied after death or sacrifice.

In the preliminary experiment, the male rat died within 22 h of dosing. Macroscopic examination of the decedent animal revealed congestive changes (characterised by dark appearance/prominent blood vessels) in the subcutaneous tissue, brain, heart, liver and spleen. Congestion with gaseous distension and fluid contents were also noted in the stomach and along the alimentary tract. Such effects were not observed in the female rat. In the main study, piloerection was observed in all rats within five minutes of dosing. This sign persisted and was accompanied in rats later on Day 1 and/or at later intervals during the study by: hunched posture, waddling/unsteady gait, lethargy, pallid extremities, walking on toes, abnormal faeces, thin appearance, ungroomed appearance and dark colouring to eyes, seen in all rats. These signs were accompanied in one or more rats by increased salivation and swollen abdomen. Recovery of surviving rats, as judged by external appearance and behaviour, was complete in all females by Day 7 and in all males by Day 10.

The oral LD50 for TMPeoTA 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 (1272/2008).