Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Not classified for Acute toxicity

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Lab not following OECD guidelines or GLP
Qualifier:
according to guideline
Guideline:
other: Internal SOP: TA300, TA120
Deviations:
not specified
Principles of method if other than guideline:
dose level tested: 5000, 2500 and 1250 mg/kg. Administrated as received. method of calculation: Weil method
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: CRL: CD (SD) BR
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
5000, 2500 and 1250 mg/kg
No. of animals per sex per dose:
5
Control animals:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 536 mg/kg bw
Based on:
test mat.
95% CL:
2 400 - 5 209
Mortality:
4/5 individuals (male and females) at 5000 mg/kg.
None at the other dose levels
Clinical signs:
other: Ataxia: at all doses, immediate to 1 hour Weaknes slight to severe: at all doses, immediate to 4 hours Prostration: at 5000 mg/kg, 1hour to 4 hours Normal state: at all doses, day 1 to day 14
Gross pathology:
none

CLINICAL SIGNS

SIGN

DOSE(mg/kg)

TIME

SEX

Ataxia

5000, 2500, 1250

 

Immediate to1 Hour

 

M,F

Weakness-Slightto Severe

5000, 2500, 1250

 

Immediate to 4 Hours

 

M,F

Prostration

5000

 

1 Hour to 4 Hours

M,F

Normal

5000, 2500, 1250

 

Day 1 to Day14

 

M,F

The test material was, at most, slightly toxic by the oral route. Abnormal clinical signs included slight to severe weakness at all dose levels, ataxia at the first hour after dosing, and prostration up to four hours after dosing at the high dose level. Eight of ten animals administered the high (5000 mg/kg) dose died within 24 hours, but all survivors appeared clinically normal from Day 1 through the observation period. The cause of death in animals dying after exposure to the test material was not determined. Treatment-related changes in those animals dying within one day of dosing included congestion, edema, and hemorrhage of the glandular gastric mucosa and reddish blue urine in the urinary bladder. No abnormalities related to administration of the test material were noted in animals surviving the observation period.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The Gavage LD50 of Ethylal on rats is 3536 mg/kg which is superior to the CLP cut off values of 2000 mg/kg
Executive summary:

The Gavage LD50 of Ethylal on rats is 3536 mg/kg which is superior to the CLP cut off values of 2000 mg/kg

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 536 mg/kg bw
Quality of whole database:
The 5 LD50 values are in the same range (all ones > the CLP cut-off value of 2000 mg/kg), which shows the high quality of the database.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 17-November 11, 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD guideline 403 and following GLP principles
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Species:
rat
Strain:
other: CRL:CD(SD)BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, MA
- Age at study initiation:
- Weight at study initiation: 212-250 g (males) and 192-224 g (females)
- Fasting period before study:
- Housing: Animals were singly housed in multicompartmented stainless steel mesh cages
- Diet (e.g. ad libitum): Certified feed (Agway Prolab Animal Diet (RMH 3000, pellets)) available ad lib
- Water (e.g. ad libitum): Water (Monroe County Water Authority) ad lib
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 36-43
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Exposures were conducted in 20 L glass bell jar inhalation chambers contained in a hood. Chambers were maintained under slight positive pressure and at 15-20 air changes per hour. Atmospheres were produced by passing metered dried oil-free compressed air over the surface of the test material contained in a 500 ml round bottom flask. Controls were treated identically to the test groups, except that exposure was to filtered air only. Temperature was determined hourly and nominal chamber concentration for the exposure was calculated.

TEST ATMOSPHERE
- Brief description of analytical method used: Chamber vapor concentrations were determined at least once per hour by a Miran IA infrared analyser equipped for automated sampling and analysis. On the morning and afternoon of the exposure, concentration of background nongaseous material was measured in the high concentration (20000 ppm) chamber relative to the control chamber in order to insure that exposure were to vapor and not aerosol.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
6 h
Concentrations:
0, 5000, 10000 and 20000 ppm
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: before and after exposure and twice daily thereafter for observations; on days 0, 3, 7, 10, 14 and at necropsy for body weight
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
Statistics:
One-way analysis of variance (ANOVA), Bartlett's test and Duncan's multiple range test using a P value ≤ 0.05 to indicate statistical significance. LC50 and its 95% CL were estimated by probit analysis using SAS Institute Inc. Version 5, 1985 (Cary, NC)
Preliminary study:
Not relevant
Sex:
male/female
Dose descriptor:
LC50
Effect level:
6 643 ppm
Based on:
test mat.
95% CL:
5 117 - 8 476
Exp. duration:
6 h
Mortality:
Males: death of 5/5 at 20000 ppm (within 3 hours into exposure); death of 5/5 at 10000 ppm (during the 6-hour exposure); no death at 5000 ppm.
Females: death of 5/5 at 20000 ppm (within 5 hours into exposure); death of 4/5 at 10000 ppm (during the 6-hour exposure); death of 2/5 at 5000 ppm (shortly after exposure).
Clinical signs:
other: During exposure: wobbly gait, lethargy and narcosis. Following exposure: For males: lethargy and gait disturbance at 5000 ppm. Corneal opacy for 1/5 on Day 7 to the end. For females: lethargy at 5000 ppm; narcosis following exposure at 10000 ppm All the
Body weight:
BW gain of all the surviving animals was comparable to control values.
Gross pathology:
Treatment-related changes were observed in the lungs and livers of all 3 exposure groups in females and the high- and middle-exposure groups of males. They were characterized as the incomplete collapse of lungs on thoratomy and enlarged livers. Failure of the lungs to collapse upon thoracotomy was probably caused by edema. The cause of the enlarged livers was not determined. Tissues were not collected for microscopic evaluation.
Inflammatory eye changes were observed in 4 female rats from the high dose group. Microscopic evaluation of the affected eyes revealed unilateral or bilateral congestion and edema of the ciliary body and hemorrhage of the choroid.
Other findings:
Aerosol measurements:
Measurements obtained with the Roco Model 225 Aerosol Particle Conter (HIAC/Royco Instruments Division, Pacific Scientific, Menlo Park, CA) revealed that an aerosol was not present.

Nominal concentrations differed from the analytical ones:

 Concentration  Low (ppm)  Intermediate (ppm)  High (ppm)
 Nominal  5000  10000  20000
 Analytical (males)  5357 ± 413 9802 ± 814  20029 ± 219
 Analytical (females)  5060 ± 181  9393 ± 840  16802 ± 4054
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The 6-hour LC50 value for males and females rats combined is 6643 ppm with a 95% confidence interval of 5117 to 8476 ppm in the acute inhalation toxicity study of diethoxymethane.
Executive summary:

An acute inhalation toxicity test was performed in the rat according to OECD guideline 401 and GLP compliance.

Groups of 5 male and 5 female rats were exposed to target vapor concentrations of 20000, 10000, 5000 or 0 ppm diethoxymethane (DEM) for 6 hours and then held for 14 days of observation. DEm caused lethargy, gait disturbance, narcosis and death in all rats, within 5 hours during exposure to 20000 ppm, and by 6 hours in all but one rat exposed to 10000 ppm. All the males and females survived exposure to 5000 ppm but 2 females died shorthly thereafter. Treatment-related gross changes in animals dying spontaneously were incomplete collapse of lungs and enlarged livers. No microscopic examinations were conducted. Other than transient narcosis, lethargy or gait disturbance following exposure, there were no compound-related clinical signs of toxicity or changes in bw gain in females which survived exposure to 5000 ppm. No treatment-related gross changes were seen in the surviving female exposed to 10000 ppm or in males exposed to 5000 ppm. Incomplete collapse of the lungs and enlarged livers were seen in females surviving exposure to 5000 ppm. Except for the microscopic examination of eyes which showed incidental inflammatory changes in 4 females exposed to 20000 ppm, no other microscopic examonations were performed. The lung and liver are sites of toxicity at these high concentrations. A no-effect level of toxicity was not determined.

The 6-hour LC50 value for males and females rats combined is 6643 ppm with a 95% confidence interval of 5117 to 8476 ppm in the acute inhalation toxicity study of DEM.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
0.032 mg/m³ air
Quality of whole database:
Acute inhalation toxicity was studied in an OECD 403 and GLP test.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Lab not following OECD guidelines or GLP
Qualifier:
according to guideline
Guideline:
other: Internal SOP: TA 310, TA 160, TA 120
Deviations:
not specified
Principles of method if other than guideline:
20 ml/kg administrated as received/ Method of calculation: Weil method
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CRL: CD (SD) BR
Sex:
male/female
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Doses:
20 ml/kg
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 mL/kg bw
Based on:
test mat.
Remarks on result:
other: 95% CL: no range calculable
Mortality:
none
Clinical signs:
other: all normal

Skin absorption: Not evident

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Not toxic by dermal route
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
20 000 mg/kg bw
Quality of whole database:
Study realized in Eastman Kodak Lab. They claimed their protocols as equivalent to GLP ones, even if older studies.

Additional information

Justification for selection of acute toxicity – oral endpoint

Informations are available from different studies:

in vivo studies: LD50 of 3536 mg/kg in a Klimisch code 2 study and LD50 of 2600 mg/kg in a Klimisch code 4 study.

in silico studies: LD50 of 4600 mg/kg in rat and 3100 mg/kg in mouse (Klimisch code 2)

Read-across: LD50> 4640.9 mg/kg (Klimisch code 2)

The result from the in vivo study with a Klimisch code 2 has been selected as supported by QSAR and read-across.

Justification for selection of acute toxicity – inhalation endpoint

Acute inhalation toxicity was studied in an OECD 403 and GLP  test. The 6-hour LC50 value for males and females rats combined is 6643 ppm with a 95% confidence interval of 5117 to 8476 ppm in the acute inhalation toxicity study of ethylal.

This endpoint was converted from ppm to mg/L and then the duration was converted (6h --> 4h).

As animals were exposed to vapours (and not to aerosol), ppm was converted into mg/L with the formula presented under point 3.1.2.3.2 of Guidance on the Application of the CLP Regulation (ECHA, 2011): ppm = 0.0245 mg/L /MW

6h LC50 = 6643 ppm * 104.15/24500 = 28.24 mg/L

Then, as the duration of exposure of 6 hours in the experiment is different from the duration of 4 hours on which the CLP Regulation is based, a duration extrapolation is necessary. As presented under Point R.7.4.4.1 of Chapter R.7a of Guidance on information requirements and chemical safety assessment (ECHA, 2008), extrapolation from 6 to 4 hours was performed using the modified Haber's Law ( Cn*t=k) with n = 3 for extrapolation to shorter duration than the duration for which the LC50 was observed: 4h LC50 = ((6h LC50)3* 6/4)1/3 = 32.32 mg/L.

With a CL50>20 mg/L, ethylal is not classified for its acute inhalation toxicity.

Justification for selection of acute toxicity – dermal endpoint

GLP equivalent study. Results are in the same direction as the other routes.

Justification for classification or non-classification

Acute oral toxicity: no classification with a LD50> 2000 mg/kg.

Acute inhalation toxicity: the 6 hours inhalation test revealed a DL50 of 6643 ppm.

As animals were exposed to vapours (and not to aerosol), ppm was converted into mg/L with the formula presented under point 3.1.2.3.2 of Guidance on the Application of the CLP Regulation (ECHA, 2011): ppm = 0.0245 mg/L /MW

6h LC50 = 6643 ppm * 104.15/24500 = 28.24 mg/L

Then, as the duration of exposure of 6 hours in the experiment is different from the duration of 4 hours on which the CLP Regulation is based, a duration extrapolation is necessary. As presented under Point R.7.4.4.1 of Chapter R.7a of Guidance on information requirements and chemical safety assessment (ECHA, 2008), extrapolation from 6 to 4 hours was performed using the modified Haber's Law ( Cn*t=k) with n = 3 for extrapolation to shorter duration than the duration for which the LC50 was observed: 4h LC50 = ((6h LC50)3* 6/4)1/3 = 32.32 mg/L.

With a CL50>20 mg/L, ethylal is not classified for its acute inhalation toxicity.

Acute dermal toxicity: no classification with a LD50> 20000 mg/kg.