Dimethyl ether

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

For a gas, exposures via dermal and oral route are not relevant.

DME does not show biological interactions, doesn't bind to receptors, and thus also doesn't undergo metabolic transformation. In these respects it resembles the noble gases.

The absorption via inhalation involves passive diffusion driven by difference in partial DME pressure between tissues and outside air concentrations until equilibrium is reached.

At very high concentrations the passive presence of DME in the membranes of cells, can lead to neuro-depression and at increasing concentrations even to narcosis. After bringing the organism back in fresh air without DME the DME will completely diffuse out of the body again, leading to a complete recovery.

Important to note for this is:

• Narcotic effects by DME are driven by peak exposures.


• The rapidity of the development of these symptoms almost ensures that the acute narcotic effects of DME is due to DME itself and not to metabolites. Repeated dose studies can be seen as consecutive daily (6-hour) acute toxicity studies. After ceasing the exposure, no DME is left in the body to exert any effect


• The concentrations needed for neuro-depressive effects, let alone narcosis, are very high. Neuro depressing effects of DME start from 4% in air. Information tests with human subjects show that from 5% in the air small effects in reaction time and typing skills start to become visible. At 10% no effects in first 10 minutes, incoordination developed after 21 minutes of exposure, and after one hour the subject was not able to perform simple tasks. At 14% in the air, narcosis occurred after 26 minutes, at with 20% after 17 minutes.
  All these levels are well above the limit concentration of 20'000 ppm relevant for hazard assessment testing (OECD GD 39) and many orders of magnitude above possible exposure concentrations, and therefore does not trigger a need for classification.


• The mechanism is a general one and also hydrocarbon gases, noble gases (and even CO2 and nitrogen from the air under pressure) can show these effects. Even though, noble gases and CO2 are exempted for registrations because of perceived lack of toxicity.


• There is no difference or specific sensitivity between organism for this effect (As the basic principle of function of neuronal cells are the same).

 

Hazard testing via inhalation involved testing concentrations up to 2.5% in air for 6 h/d for 2 years (25'000 ppm), which can be regarded as consecutive daily (6-hour) acute toxicity studies for 2 years, at concentrations higher than the concentration that is relevant for single (4-hour) acute inhalation studies to be used for hazard testing of gases of 20'000 ppm (OECD GD 39), and has not shown adverse effects. The anaesthetic effects of DME are therefore only observed at concentrations that are of no relevance anymore for testing, and classification.

 

Exposure assessment indicates that the highest estimated exposures are for:

• Production: 95.97 mg/m3 (50 ppm) involving PROC 15: QC sampling.


• Formulation: (transfer of gases under pressure) has maximum estimated exposure of 383.9 mg/m3 (201 ppm) for PROC 9 (Transfer of substance or mixture into small containers)


• Industrial/professional uses: maximum exposures result from professional spraying estimated by ECETOC TRA 3.0 to be 1340 mg/m3 (701 ppm). Other uses as degreaser, production of foam boards and uses as fuel additive result to considerably lower estimated exposures.


• Consumer uses: Highest estimated exposures come from use as propellant, specifically from PC 3 propellants in air care products(ConsExpo web 1.1.0), with estimated maximum exposures of 520 mg/m3 (272 ppm). Indirect exposures from service life of foam article leads to negligible exposures (ConsExpo web 1.1.0) of 33 mg/m3 (17 ppm).

 

Considering that for DME no toxicological hazard has been identified up to 25'000 ppm, above the limit concentrations of 20'000 ppm for gases in air relevant for hazard testing, in several species tested (rat, mouse, hamster), and that the inert properties of DME are such that this will not be different in other species and sensitive individuals, the following approach could be taken for tentative DNEL calculation:
Conversion of 6hr NOAECrat 20'000 ppm to 8hr NOAECworkers would lead to a DNEL of 14'000 ppm (26900 mg/m3), and 24 hr NAOECconsumers of 5000 ppm (9550 mg/m3) of DME in the air.
(still conservative as lower corrected NOAEChuman for inhalation rates is not applicable for passive diffusion of gases: the level of equilibrium air/tissues is the same; only duration until equilibrium is reached differs between different organisms: the larger the longer it takes)

 

To put this into perspective, a comparison can be made to Carbon dioxide, a gas exempted from REACH registration based on lack of hazards. The physico-chemical properties of DME and CO2 are very comparable. Also its toxicological profile indicates not much effects at 2% or below (same as DME). In concentrations up to 1% (10,000 ppm), CO2 will make some people feel drowsy and give the lungs a stuffy feeling (at lower concentration than DME). The majority of the studies reported that chronic low concentration of CO2 induces low to mild effects: visual impairment occurred at 1% CO2 and headaches were noticed in the first days of exposure above 2%. The substance is teratogenic at high conc. (at 6% after only a single day exposure between gd 5-20).

For CO2 a TWA of 5000 ppm (9000 mg/m3) has been set  [2006/15/EG (7-2-2006)]

The background concentration in air is 415 ppm (already higher than highest DME exposures for consumers); In urban areas concentrations are generally higher and indoors they can reach10 times background levels! (Resulting to a RCR of 0.8 for workers without any additional exposures from uses).

Carbon dioxide has considerable higher consumer uses then DME. It is used in the production of carbonated beverages, as fire extinguisher and as refrigerant. Despite the relative high uses and consequent exposures, the use of carbon dioxide is (justly) considered safe and even exempted from REACH requirements.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

DME is a gas and potential exposure would likely occur via the inhalation route. Exposures via dermal and oral route are not relevant.

DME does not show biological interactions, doesn't bind to receptors, and thus also doesn't undergo metabolic transformation. In these respects it resembles the noble gases.

The absorption via inhalation involves passive diffusion driven by difference in partial DME pressure between tissues and outside air concentrations until equilibrium is reached.

At very high concentrations the passive presence of DME in the membranes of cells, can lead to neuro-depression and at increasing concentrations even to narcosis. After bringing the organism back in fresh air without DME the DME will completely diffuse out of the body again, leading to a complete recovery. 

Important to note for this is:

• Narcotic effects by DME are driven by peak exposures.


• The rapidity of the development of these symptoms almost ensures that the acute narcotic effects of DME is due to DME itself and not to metabolites. Repeated dose studies can be seen as consecutive daily (6-hour) acute toxicity studies. After ceasing the exposure, no DME is left in the body to exert any effect.


• The concentrations needed for neuro-depressive effects, let alone narcosis, are very high. Neuro depressing effects of DME start from 4% in air. Information tests with human subjects show that from 5% in the air small effects in reaction time and typing skills start to become visible. At 10% no effects in first 10 minutes, incoordination developed after 21 minutes of exposure, and after one hour the subject was not able to perform simple tasks. At 14% in the air, narcosis occurred after 26 minutes, at with 20% after 17 minutes.
  All these levels are well above the limit concentration of 20'000 ppm relevant for hazard assessment testing (OECD GD  39) and many orders of magnitude above possible exposure concentrations, and therefore does not trigger a need for classification.


• The mechanism is a general one and also hydrocarbon gases, noble gases (and even CO2 and nitrogen from the air under pressure) can show these effects. Even though, noble gases and CO2 are exempted for registrations because of perceived lack of toxicity.


• There is no difference or specific sensitivity between organism for this effect (As the basic principle of function of neuronal cells are the same).

Hazard testing via inhalation involved testing concentrations up to 2.5% in air for 6 h/d for 2 years (25'000 ppm), which can be regarded as consecutive daily (6-hour) acute toxicity studies for 2 years, at concentrations higher than the concentration that is relevant for single (4-hour) acute inhalation studies to be used for hazard testing of gases of 20'000 ppm (OECD GD 39), and has not shown adverse effects. The anaesthetic effects of DME are therefore only observed at concentrations that are of no relevance anymore for testing, and classification.

Exposure assessment indicates that the highest estimated exposures are for:

• Production: 95.97 mg/m3 (50 ppm) involving PROC 15: QC sampling.


• Formulation: (transfer of gases under pressure) has maximum estimated exposure of 383.9 mg/m3 (201 ppm) for PROC 9 (Transfer of substance or mixture into small containers)


• Industrial/professional uses: maximum exposures result from professional spraying estimated by ECETOC TRA 3.0 to be 1340 mg/m3 (701 ppm). Other uses as degreaser, production of foam boards and uses as fuel additive result to considerably lower estimated exposures.


• Consumer uses: Highest estimated exposures come from use as propellant, specifically from PC 3 propellants in air care products (ConsExpo web 1.1.0), with estimated maximum exposures of 520 mg/m3 (272 ppm). Indirect exposures from service life of foam article leads to negligible exposures (ConsExpo web 1.1.0) of 33 mg/m3 (17 ppm).

 

Considering that for DME no toxicological hazard has been identified up to 25'000 ppm, above the limit concentrations of 20'000 ppm for gases in air relevant for hazard testing, in several species tested (rat, mouse, hamster), and that the inert properties of DME are such that this will not be different in other species and sensitive individuals, the following approach could be taken for tentative DNEL calculation:
Conversion of 6hr NOAECrat 20'000 ppm to 8hr NOAECworkers would lead to a DNEL of 14'000 ppm (26900 mg/m3), and 24 hr NAOECconsumers of 5000 ppm (9550 mg/m3) of DME in the air.
(still conservative as lower corrected NOAEChuman based on inhalation rates is not applicable for passive diffusion of gases: the level of equilibrium air/tissues is the same; only duration until equilibrium is reached differs between different organisms: the larger the longer it takes)

 

To put this into perspective, a comparison can be made to Carbon dioxide, a gas exempted from REACH registration based on lack of hazards. The physico-chemical properties of DME and CO2 are very comparable. Also its toxicological profile indicates not much effects at 2% or below (same as DME). In concentrations up to 1% (10,000 ppm), CO2 will make some people feel drowsy and give the lungs a stuffy feeling (at lower concentration than DME). The majority of the studies reported that chronic low concentration of CO2 induces low to mild effects: visual impairment occurred at 1% CO2 and headaches were noticed in the first days of exposure above 2%. The substance is teratogenic at high conc. (at 6% after only a single day exposure between gd 5-20).

For CO2 a TWA of 5000 ppm (9000 mg/m3) has been set  [2006/15/EG (7-2-2006)]

The background concentration in air is 415 ppm (already higher than highest DME exposures for consumers); In urban areas concentrations are generally higher and indoors they can reach10 times background levels! (Resulting to a RCR of 0.8 for workers without any additional exposures from uses).

Carbon dioxide has considerable higher consumer uses then DME. It is used in the production of carbonated beverages, as fire extinguisher and as refrigerant. Despite the relative high uses and consequent exposures, the use of carbon dioxide is (justly) considered safe and even exempted from REACH requirements.