[2-(2-methoxymethylethoxy)methylethoxy]propanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-study according to OECD guideline 401.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

[2-(2-methoxymethylethoxy)methylethoxy]propanol

EC Number:

247-045-4

EC Name:

[2-(2-methoxymethylethoxy)methylethoxy]propanol

Cas Number:

25498-49-1

Molecular formula:

C10H22O4

IUPAC Name:

[2-(2-Methoxymethylethoxy)methylethoxy]propanol

Details on test material:

"Dowfroth 250E" (polypropylene glycol methyl ether)
Batch No.: 120286 21.3.86
Purity: 90% polypropylene glycol methyl ether (tri- and higher).
Supplied as: Metal screw-top container.
Appearance : Clear brown liquid.
Administered as : Pure liquid.
Specific Gravity : 0.973.
Solubility: Not specified.
Stability : Not specified.

Test animals

Species:

rat

Strain:

other: Sprague-Dawley CFY

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna (UK) limited, Wyton, Huntingdon
- Age at study initiation: Males: 121-151 g and females: 101-136 g
- Weight at study initiation: Approximately five to eight weeks old
- Fasting period before study: overnight fasting immediately before dosing
- Housing: The animals were housed in groups of up to five by sex in polypropylene cages with sawdust bedding
- Diet (e.g. ad libitum): Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U. K.
- Water (e.g. ad libitum): Drinking water ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22º C
- Humidity (%): 45-65 %
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness


IN-LIFE DATES: not specified

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: none

Details on oral exposure:

Four groups of Sprague-Dawley rats (5/sex/dose level) received single  oral doses of 2300, 3000, 3900, or 5000 mg/kg polypropylene glycol methyl  ether (PPM), administered undiluted using a stainless steel stomach cannula attached to a syringe.  Animals were fasted overnight prior to  dosing. The specific gravity was determined and used to calculate the appropriated dose volumes for the required dose levels.

Doses:

2300, 3000, 3900 and 5000 mg/kg

No. of animals per sex per dose:

5 rats/sex/dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 1 and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded on the day of treatment (day 0), days 7 and 14 and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathological examinations

Statistics:

LD50's and 95% confidence limits were calculated for both sexes  individually and combined using the method of Weil (Biometrics 8:249,  1952).

Results and discussion

Preliminary study:

A preliminary study was performed using groups of two rats (one male and one female) to determine suitable dose levels for the main study. The doses were 500, 1000, 2000, 4000 and 8000 mg/kgbw. Animals were observed 1 and 4 hours after dosing and then daily for five days, or until all evidence had subsided, whichever was longer. Bodyweights were recorded on the day of dosing. No necropsies were performed. Mortalities occured at the dose level of 8000 mg/kgbw (2/2). The mortalities indicated an oral LD50 of between 4000 and 8000 mg/kg.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 500 mg/kg bw

95% CL:

>= 3 100 - <= 3 900

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

3 600 mg/kg bw

95% CL:

>= 3 100 - <= 4 200

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

3 400 mg/kg bw

95% CL:

>= 2 900 - <= 4 100

Mortality:

Males:-
2300 mg/kg: 0/5
3000 mg/kg: 1/5
3900 mg/kg: 3/5
5000 mg/kg: 5/5

Females:-
2300 mg/kg: 0/5
3000 mg/kg: 2/5
3900 mg/kg: 3/5
5000 mg/kg: 5/5

Clinical signs:

other: Symptoms in survivors exhibited a dose-response relationship and included  hunched posture, lethargy, piloerection, decreased respiratory rate,  ptosis, body tremors, and red/brown staining around the eyes or snout at  all dose levels.  Other more severe 

Gross pathology:

Necropsy of survivors revealed congested lungs in 4 males  and 4 females from the 2300 mg/kg group but not in the 3000 or 3900 mg/kg  groups.

Other findings:

None

Any other information on results incl. tables

Mortality is shown in the table below:

Dose Level(mg/kg)	Mortalities
	Male	Female	Both Sexes	Percentage
2300	0/5	0/5	0/10	0
3000	1/5	2/5	3/10	30
3900	3/5	3/5	6/10	60
5000	5/5	5/5	10/10	100

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

With an oral LD50 of 3500 mg/kg, polypropylene glycol methyl ether shows a low degree of acute toxicity. This test material is appears to be comprised largely of tripropylene glycol methyl ether.

Executive summary:

Twenty five male and twenty five female Sprague Dawley CFY strain rats were used. Animals were acclimatized for a minimum period of five days. At the start of the main study the males weighed 121-151 g, and the females 101-136 g, and were approximately five to eight weeks old. The animals were housed in groups of up to five by sex in polypropylene cages with sawdust bedding. With the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and food was allowed throughout the study.

The animal room was maintained at a temperature of 19-22º C and relative humidity of 45-65%. The rate of air exchange was approximately 15 changes per hour.

Following an initial range-finding study, four groups, each of ten rats (five males and five females) were given a single oral dose of test material at dose levels of 2300, 3000, 3900 and 5000 mg/kg bodyweight.

Animals were observed 1 and 4 hours after dosing and subsequently once daily for 14 days. Mortalities and evidence of overt toxicity were recorded at each observation. Individual bodyweights were recorded on the day of treatment (day 0), days 7 and 14 and at death. All animals were subjected to gross necropsy examination for any microscopic abnormalities. No tissues were retained.

Symptoms in survivors exhibited a dose- response relationship and included hunched posture, lethargy, piloerection, decreased respiratory rate, ptosis, body tremors and red/ brown staining around the eyes or snout at all dose levels. Other more severe symptoms occurring more often at higher dose levels included coma and gasping respiration. By day 2, symptoms had disappeared in the two lower dose levels and by day 3 in survivors from the 3900 mg/kg group.

Deaths occurred in a dose related manner (3/10 at 3000 mg/kg, 6/10 at 3900 mg/kg and 10/10 at 5000 mg/kg). All rats which died did so within 24 hours of dosing and survivors recovered from the non-specific signs of toxicity within 3 days of dosing. Some survivors were reported to have congested lungs at necropsy after 14 days observation but most were unremarkable.

The LD50 in rats for Dowfroth 250E was 3600 mg/kg for males, 3400 mg/kg for females and 3500 mg/kg for the sexes combined (3100-3900 mg/kg 95% confidence limits). As the LD50 of the test material was greater than 2000 mg/kg, Dowfroth 250E was not classified as toxic as per EU classification.