Registration Dossier

Administrative data

Description of key information

ORAL - RATS (mg/kg)

TEGME: LD50: >10500, 11.3ml/kg

TetraEGME LD50: >15000 mg/kg; >2000mg/kg

Mix of tri, tetra and penta methyls: >5000mg/kg

DERMAL LD50 (mg/kg)

TEGME: Rat: Rabbit: 7.45mL/kg

Mix of tri, tetra and penta methyls: Rat LD0: >2000mg/kg, >4mL/kg

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:
weight of evidence
Study period:
19 Feb 1974 - 01 Mar 1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Method: BASF-Test which follows in principle the methods described in OECD Guideline 401.
5 rats per sex and dose were treated simultaneously by gavage with preparations of the test substance in water. Group-wise documentation of clinical signs was performed over the 7 day study period. The clinical signs and findings were reported in summary form.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: male: 186g (mean), female 165g (mean)

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 35% for 10500 mg/kg and 15% for 1050 and 2257 mg/kg
Doses:
1050, 2257, 10500 mg/kg bw
No. of animals per sex per dose:
5 male and 5 female rats per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
Statistics:
On the basis of the observed lethality, the LD50 value was estimated or determined using a graphical evaluation of the dose response curve on probability paper.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 500 mg/kg bw
Mortality:
no mortality occured.
Clinical signs:
Signs of toxicity comprised at 10500 mg/kg: apathy, spastic gait, dyspnea, mouth and eyelid crust formation.
Body weight:
See table below
Gross pathology:
At necroscopy no abnormalities were observed.

Mean Body weights (g) MALES:

Dose group (mg/kg)

Day 0

Day 3

Day 7

1050

190

210

205

2257

199

228

222

10500

169

124

159

 

Mean Body weights (g) FEMALES:

Dose group (mg/kg)

Day 0

Day 3

Day 7

1050

165

184

167

2257

163

178

170

10500

168

192

178

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

In an acute oral toxicity study that followed the basic requirements of the OECD standard protocol guideline, male and female rats were exposed to single gavage doses of 2 -(2 -(2 -methoxyethoxy)ethoxy)ethanol at doses up to 10500mg/kg. The high dose animals showed apathy, spastic gait, dyspnea, mouth and eyelid crust formation and males also showed a sharp but transient drop in body. However, no mortality was reported implying that the LD50 is significantly in excess of the maximum dose tested.

Synopsis

LD50 (male, female) >10500mg/kg

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 500 mg/kg bw

Acute toxicity: via inhalation route

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:
weight of evidence
Study period:
1960-62
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Acceptable, study containing basic data which suggests that basic scientific principles have been met. This is sufficient to judge the results reliable as a contribution to the understanding of the toxicity of this substance.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Study pre-dates guidelines. Similar to one day cuff method of Draize (J Pharmac Exp Therap, 82, 377, 1944)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: ~2.5kg
- Age at study initiation: 3-5 months.
- Other: albino rabbits used.
- Diet: Rockland rabbit diet
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Fur removed from entire trunk area by clipping
- % coverage:
- Type of wrap if used: impervious plastic film (VINYLITE)

OTHER
- Animals immobilised during 24 hour exposure period.
Duration of exposure:
24 hours
Doses:
2.5, 5.0, 10, 20ml/kg
No. of animals per sex per dose:
2, 4, 2, 1 respectively.
Control animals:
other: no but a large number of other substances also tested which acted as reference materials.
Details on study design:
- Duration of observation period following administration: 14 days after wrap removed following 24 hour exposure.
Statistics:
The moving average method was used to calculate the LD50
Sex:
male
Dose descriptor:
LD50
Effect level:
7.1 mL/kg bw
Mortality:
All animals in top two dose groups died but none in lower two dose groups.
Clinical signs:
Marked erythema seen. Otherwise no signs in lower two dose groups.
Body weight:
5g/ml: Two animals showed normal weight gain, one little weight gain and one weight loss. 2.5ml/kg: One showed normal and one minimal weight gain.
Gross pathology:
Hihg dose animal and one of the 10ml/kg animals showed internal and lung hemorrhage. Livers were congested and kidneys pale and possibly swollen.

Results:

Dose (ml/kg)

Mortality

Day of death

Average weight gain (g)

10

2/2

Both day 4

 

5

0/4

-          

135 (SD=163)

2.5

0/2

-          

100 (SD=130)

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

In an acute dermal toxicity in rabbits in which key basic details were reported, an LD50 of 7.1ml/kg was obtain. Exposure was under occluded conditions.

Synopsis

LD50=7.1ml/kg

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

A number of LD50 studies are available in rats using the substances methyl triglycol and methyl tetraglycol, two main components of this UVCB/multicomponent substance, and mixtures containing significant amounts of these substances. All consistently show that the LD50 is very high. The key study selected is considered representative of the UVCB/multicomponent substance and shows that an LD50 was not identified at the maximum tested dose of 10500mg/kg. This conclusion is supported by the read across justification document attached to chapter 13 of the lead registrant's dossier. In a poisoning case, a young child self administered a huge dose estimated in excess of 25g/kg of a formulated brake fluid based on triethylene glycol ethers. Whilst intensive medical support was briefly required, the patient made a full recovery.

Acute dermal toxicity data is available in both the rat and rabbit for tri and tetraethylene glycol methyl ether and formulations containing these substances. An LD50 of ~7.5mL/kg was established in the rabbit whilst a figure of >2000mg/kg was established in the rat from a recent GLP limit study using a mixture of primarily tri, tetra and penta ethylene glycol methyl ethers. In a sub-chronic dermal toxicity study using rats (reported in chapter 7.5.2) a NOAEL of 4000mg/kg was established, indicating that the acute LD50 must be significantly in excess of this. Based on the low dermal absorption rate of the substance, (see chapter 7.1.2), acute toxicity by the dermal route would not be expected. This conclusion is supported by the read across justification document attached to chapter 13 of the lead registrant's dossier.

There is no acute studies by inhalation available for this UVCB/multicomponent substance. Taking into account the very low volatility and uses of this substance, along with the acute data from other routes, it can be concluded that there is no hazard from the inhalation of saturated vapour concentrations at ambient temperatures.

Based on observations from the lower members, higher molecular weight species in this homologous series of polyalkylene glycol methyl ethers will show decreasing potential for acute toxicity so these results can be considered representative of this UVCB/multicomponent substance.

Justification for classification or non-classification

Base on the available data, the substance clearly does not meet the criteria for classification for acute toxicity by any route of exposure.