Ethylene oxide

Endpoint summary

Description of key information

Acute oral toxicity:

Smyth et al. (1941): non-guideline, non-GLP study in rat and guinea-pig, non-specified dose levels applied as a 1% aqueous solution. LD50 (male rats): 330.0 mg/kg bw. For male and female guinea pigs, LD50 was 270 mg/kg bw.

Hollingsworth et al. (1956): non-guideline, non-GLP in rats exposed to 100 and 200 mg/kg bw. LD0: 100 mg/kg bw, LD100: 200 mg/kg bw.

Acute inhalation toxicity:

US NTP (1987): Similar to OECD 403, whole-body exposure, GLP unspecified, 5 mice per dose and sex exposed for 4h at dose levels between 100 and 1600 ppm. The lowest LC50 value was 660 ppm (95% CI 509-856 ppm) as calculated for female mice. This corresponds to 1189 mg/m3 air.

Snellings et al. (2011): non-guideline, GLP, using 5 rats per sex per dose exposed for 4-h at dose levels between 1443 ppm – 2182 ppm. The LC50 was established to be 2767.0 mg/m³ and 3550.0 mg/m³ for female and male rats, respectively.

Acute dermal toxicity:

No experimental study is available. However, extensive skin burns with blister formation have been described as the result of exposure to aqueous solutions; this effect has been repeatedly observed over many years by physicians working in the industry. Excessive skin burns are also reported in animal studies and ethylene oxide is classified for corrosivity to skin.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Publication describes investigation of many substances and the procedures are generally described with indication of exemptions in some cases. These cases are not specified so that it is not possible to definately retrace the conditions for one specific substance.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

less reporting destails. Body weights not reported. Only males examined.

GLP compliance:

no

Test type:

fixed dose procedure

Specific details on test material used for the study:

Commercial grade

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Commercial breeders
- Weight at study initiation: 250-300 g
- Diet: ad libitum. Diet was given in the afternoon, doses the following morning.
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Any victim whose death was inconsistent with the indications from others receiving the substance was atopsied, and if found to be infected it was not included in the calculations. Tissues were not studied microscopically because this step was beyond the scope of the preliminary investigation planned.
The data were calculated by method of probits, described by Bliss (1935) and now becoming familiar. No attempt was made to use adequate animals to obtain extreme precision in the LD50 figure, for the use to which such information is put seldom justified extreme accuracy. The precision is indicated by the range of 95% probability.

Doses:

Max concentration fed: 1%
The exact dosages were not reported. Enough dosages were administered to include those at which no animal died and those at which all died. Most deaths occurred with the first 2 days, but all deaths within 14 days of administration of the dose were considered in calculating the LD50.

No. of animals per sex per dose:

Indicated to be generally 10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

no data

Sex:

male

Dose descriptor:

LD50

Effect level:

330 mg/kg bw

Based on:

test mat.

95% CL:

> 290 - < 360

Mortality:

Death was delayed about a week; and if deaths only within the first 2 days had been considered, the LD50 reported would usually have been much higher.

Clinical signs:

other: Fatal or near fatal doses produced no narcosis but varying degrees of sluggish depressed functioning. The test substance caused narcosis but in most cases only at the LD50 or above.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In summary, male rats were exposed to concentrations of up to 1% resulting in an LD50 of 330 mg/kg bw.

Executive summary:

An acute oral toxicity study was conducted using ten male Wistar rats exposed to concentrations of 1% as a maximum using the fixed dose procedure. A 14-day observation period was performed and necropsy and clinical signs were performed. Death was delayed about a week; and if deaths only within the first 2 days had been considered, the LD50 reported would usually have been much higher. Fatal or near fatal doses produced no narcosis but varying degrees of sluggish depressed functioning. The test substance caused narcosis but in most cases only at the LD50 or above. The LD50 was reported to be 330 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Little detailed information, body weights not reported.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no body weight reported

Principles of method if other than guideline:

Determination of LD50

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

commercial grade

Species:

guinea pig

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Commercial breeders
- Weight at study initiation: 250-300 g
- Diet: ad libitum. Diet was given in the afternoon, doses the following morning.
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1%

Doses:

Exact doses were not reported. The greatest concentration employed was 1%.

No. of animals per sex per dose:

Indicated to be generally 10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not reported
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

270 mg/kg bw

Based on:

test mat.

95% CL:

> 190 - < 380

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The LD50 of exposed female and male guinea pigs was 270 mg/kg bw.

Executive summary:

An acute oral toxicity study was conducted using ten male and female guinea pigs exposed to concentrations of 1% as a maximum using the fixed dose procedure. A 14-day observation period was performed and necropsy and clinical signs were performed. The LD50 was reported to be 270 mg/kg bw.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Single oral gavage dosing with 13-day observation period. pre-GLP study.

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

purity was 97.0% - 98.6% (w/w) by both chemical and mass spectroscopic analysis
impurities 0.7% acetylene and 2.3% air by mass spectrometry

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

young animals, bred from colony of the testing laboratory

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

10% concentration in vehicle, cold ethylene oxide was used.
Concentrations were verified analytically.

Doses:

100 and 200 mg/kg bw

No. of animals per sex per dose:

5 in sum for both sexes

Control animals:

not specified

Details on study design:

13 day observation period

Sex:

male/female

Dose descriptor:

LD0

Effect level:

100 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD100

Effect level:

200 mg/kg bw

Based on:

test mat.

Mortality:

All animals died after the single dose of 200 mg/kg bw, whereas all animals survived dosing with 100 mg/kg bw during the 13-day observation period.

Clinical signs:

other: not reported

Gross pathology:

not reported

Other findings:

not reported

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Single doses of 0.1 mg/kg allowed the survival of all animals and doses  of 0.2 mg/kg killed all animais. All survivors gained weight in a normal  manner during the post-feeding observation period of 9 to 13 days.

Executive summary:

An acute oral toxicity study was conducted using five young male and female rats in sum exposed to 100 and 200 mg/kg bw using the fixed dose procedure. A single oral gavage dosing with a 13-day observation period was performed. A 10% concentration dissolved in olive oil was used. Concentrations were analytically verified. All animals died after the single dose of 200 mg/kg bw, whereas all animals survived dosing with 100 mg/kg bw during the 13-day observation period. Surviving animals showed normal body weight gain. The LD0 and LD100 was 100 mg/kg bw and 200 mg/kg bw, respectively.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

270 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

No necropsy performed

GLP compliance:

not specified

Test type:

fixed concentration procedure

Limit test:

no

Specific details on test material used for the study:

purity: >99%

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, USA
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Age at study initiation: 8 - 10 weeks
- Housing: Single
- Diet: ad libitum
- Water: ad libitum)
- Acclimation period: 28 days

ENVIRONMENTAL CONDITIONS
- Temperature (Fahrenheit): 70 - 72
- Humidity (%): 40 - 60%
- Air changes (per hr): 10 during exposure, 20 at all other times
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: February 2, 1980 To February 21, 1980

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Liquefied ethylene oxide was dispensed through an eductor tube from the 175-pound cylinder to a coiled-tube hot water boiler by pressurizing the tankhead space with nitrogen (regulated at 20 psi). The vapor was generated in a stainless steel coiled tube boiler located in a 55° ± 10° C water bath. From the boiler, ethylene oxide vapor was routed through a manifold to dual gas metering valves that controlled the gas flow to each chamber. The manifold and valves were heated to about 55° C with a heat tape and a small heater.

Vapor to each chamber was routed through a three-way purge/expose valve into a pipe at the chamber inlet, where the gas was mixed with 0.28 ± 0.04 m3/min of diluent air.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Target: 100, 200, 400, 800 and 1600 ppm (measured: 96, 201, 409, 816 and 1542 ppm)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mice were observed continuously during the exposure period and three times per day during nonexposure periods. They were weighed only before exposure.
- Necropsy of survivors performed: no

Sex:

female

Dose descriptor:

LC50

Effect level:

660 ppm

Based on:

test mat.

95% CL:

> 509 - < 856

Exp. duration:

4 h

Remarks on result:

other: corresponds to 1189 mg/m3 air)

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 660 ppm

Based on:

test mat.

Exp. duration:

4 h

Mortality:

All mice exposed at 1,600 ppm and 5/5 males and 4/5 females exposed at 800 ppm died before the end of the studies.

Clinical signs:

other: At 800 ppm, lacrimation was observed after 3 hours; dyspnea was observed after 4 hours. At 1,600 ppm, dyspnea, lacrimation, and incoordination were observed after 3 hours; semiconsciousness, severe dyspnea, and diarrhea were observed after 3.5 hours.

Body weight:

not determined

Gross pathology:

not performed

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The LC50 for 4h whole body exposure of mice is ca 660 ppm (1189 mg/m3 air).

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

other: United States Department of Transportation guideline protocol

Version / remarks:

1990s. This protocol was used to conduct the 1-h LC50 study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Remarks:

Indicated to be GLP compliant in the publication

Test type:

fixed concentration procedure

Limit test:

no

Specific details on test material used for the study:

INFORMATION ON TEST MATERIAL FOR THE 4-HOUR EXPOSURE STUDY
- Source: Union Carbide Corporation
- Purity: 99.9%
- Appearance: liquid
- Storage condition: stainless-steel gas cylinder partially filled with liquid ethylene oxide

INFORMATION ON TEST MATERIAL FOR THE 1-HOUR EXPOSURE STUDY
- Source: Union Carbide Corporation
- Purity: Different concentrations of the test substance in air (ranging from 4000 to 7000 ppm)
- Storage conditions: stainless-steel gas cylinders

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague-Dawley, Inc., Indianapolis, Ind, USA
- Age at study initiation: approximately six weeks
- Weight at study initiation: 4-hour exposure group weight: 220-280 kg males, 180-195 kg for females; for 1-hour exposure group weight: 250-285 kg for males, 185-200 kg for females
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 to 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Remarks:

filtered air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 4-hour exposure: The gas cylinder was maintained at approximately 35°C in a water bath. The resulting headspace of vapour was regulated through stainless-steel tubing and delivereed through a calibrated flowmeter into a mixing chamber with filtered-room air before being carried into the inhalation chamber (under negative pressure).
1-hour: Same procedure as described above, but the concentration of the test sustance was, when necessary, diluted with filtered-room air before delivery into the inhalation chamber.
- Exposure chamber volume: 1300-liter (4-hour), 120-liter (1-hour)
- Method of holding animals in test chamber: individually housed in a wiremesh cage
- Rate of air: The calibrated chamber airflow rate was approximately 300 l/min (4-h); 30 l/min (1-h)

TEST ATMOSPHERE
- Brief description of analytical method used: A Perkin-Elmer Model 8500 or 3920B gas chromatograph (GC) quipped with a flame ionization detector was used
- Samples taken from breathing zone: yes, approximately every 15 minutes (1-h) or every 30 minutes (4-h)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

>= 1 - <= 4 h

Remarks on duration:

One group was exposed for 1 hour and another group was exposed for 4 hours

Concentrations:

4-h exposure: 1443 ppm, 1637 ppm, 1850 ppm (female rats); 1850 ppm, 2026 ppm, 2182 ppm (male rats)
1-h exposure: 3966 ppm, 4202 ppm, 4827 ppm (female rats); 4827 ppm, 5546 ppm, 6161 ppm (male rats)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clincial signs and adverse effects were observed before randomization into groups (once), during (approximately every 10 minutes) and after (at least once daily) exposure. Body weight was assessed before randomization and post-exposure days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (lungs)

Statistics:

The mean and standard deviation of the body weights, body weight changes, lung weights (4-hour exposure only), and exposure concentrations were calculated. No statistical comparisons were made. The LC50 values were determined by the moving average method of Thompson for males, females and the combined sexes. For calculation of the combined sexes, where there was no exposure for a particular sex because it was predetemined from prior exposures that the results would have been either all deaths or no deaths, the appropriate expected ratio (5/5 or 0/5) was used in order to permit calculation of the LC50 value for the
combined sexes.

Sex:

male

Dose descriptor:

LC50

Effect level:

3 550 mg/m³ air

Based on:

test mat.

95% CL:

>= 3 397 - <= 3 710

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC50

Effect level:

2 767 mg/m³ air

Based on:

test mat.

95% CL:

>= 2 504 - <= 3 056

Exp. duration:

4 h

Mortality:

4-h exposure group: One male rat died within 1 h following exposure to the highest dose (2182 ppm). All remaining deaths occurred within three days following exposure.
1-h exposure group: No rats died during the 1-h exposure period. All remaining deaths occurred within two days following exposure.

Clinical signs:

other: Ocular and nasal irritation, irregular breathing, absence of certain reflexes, ataxia, and tremors (both 1-h, and 4-h exposure groups). 4-h exposure group: No clinical signs were observed in survivors after postexposure day 5. 1-h exposure group: No clin

Body weight:

All body weight changes showed an increase at postexposure day 7 and day 14 (no statistics were conducted).

Gross pathology:

Diffuse or multifocal discoloration of the lungs and hyperinflation of the lungs (animals that died). Clear fluid in the thoracic cavity was recorded in one male and one female that died in the highest exposure groups in the 1-h study.
Focal or multifocal color change of the lungs in euthanized animals on day 14.

Other findings:

- Organ weights: All lung weights were in the normal range (4-h study only)
- Histopathology: Treatment-related microscopic lesions were seen in all the lungs of males of the 2182 ppm group and in all females of the 1850 ppm group that died. Principal lung lesion was moderate to severe pulmonary congestion. Other lesions included mild hemorrhage, pulmonary edema, and emphysema.
- Potential target organ: lung

The LC50 for males and females after an exposure period of 1 -hr was 10,346.0 mg/m³ and 7,990.0 mg/m³, respectively, with a 95% confidence interval of ≥9,497.0≤11,272.0 and ≥7,61.0≤8,791.0, respectively.

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

In addition, a specific target organ toxicity - single exposure category 3 is interpreted based on the presented results.

Conclusions:

The LC50 obtained in the current acute inhalation toxicity study in Sprague-Dawley rats exposed to 4 hours and 1 hour was 3550 mg/m³ (males), 2767 mg/m³ (females) and 10,346 mg/m³ (males), 7990 mg/m³ (females), respectively. The LC50 of the combined sexes exposed for 4 h and 1 h was 3134 mg/m³ and 9052 mg/m³, respectively.

Executive summary:

Ethylene oxide was tested on groups of rats both for a 4 -hour and a 1 -hour inhalation exposure, followed by 14 days of observation. Groups of five Sprague-Dawley rats/sex were exposed, and clinical signs and mortality was recorded. Clinical signs noted included irregular breathing, absence of certain reflexes, and tremors. Rats that died had moderate to severe pulmonary congestion. The calculated LC50 values, reported as ppm by volume (with 95% confidence limits), were as follows.:Four-hour LC50 values were 1972 (1887 to 2061) ppm for males; 1537 (1391 to 1698) ppm for females; 1741 (1655 to 1831) ppm for the combined sexes. The 1 -hour LC50 values were 5748 (5276 to 6262) ppm for males; 4439 (4034 to 4884) ppm for females; 5029 (4634 to 5459) ppm for the combined sexes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 189 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

An acute oral toxicity study was conducted using five young male and female rats in sum exposed to 100 and 200 mg/kg bw using the fixed dose procedure. A single oral gavage dosing with a 13-day observation period was performed. A 10% concentration dissolved in olive oil was used. Concentrations were analytically verified. All animals died after the single dose of 200 mg/kg bw, whereas all animals survived dosing with 100 mg/kg bw during the 13-day observation period. Surviving animals showed normal body weight gain. The LD0 and LD100 was 100 mg/kg bw and 200 mg/kg bw, respectively (Hollingsworth et al., 1956).

An acute oral toxicity study was conducted using ten male Wistar rats exposed to concentrations of 1% as a maximum using the fixed dose procedure. A 14-day observation period was performed and necropsy and clinical signs were performed. Death was delayed about a week; and if deaths only within the first 2 days had been considered, the LD50 reported would usually have been much higher. Fatal or near fatal doses produced no narcosis but varying degrees of sluggish depressed functioning. The test substance caused narcosis but in most cases only at the LD50 or above. The LD50 was reported to be 330 mg/kg bw (Smyth et al., 1941).

An acute oral toxicity study was conducted using ten male and female guinea pigs exposed to concentrations of 1% as a maximum using the fixed dose procedure. A 14-day observation period was performed and necropsy and clinical signs were performed. The LD50 was reported to be 270 mg/kg bw (Smyth et al., 1941).

In addition, a study by Woodard et al. (1971) exposing rats, mice, and rabbits support the aforementioned results. The LD50 for rats, mice, and rabbits were reported to be 240, 280, 630 mg/kg bw for females and 280, 360, and 630 mg/kg bw for males, respectively.

Acute inhalation toxicity:

An acute inhalation toxicity study was performed as part of the US National Toxicology programm with male and female B6C3F1 mice in 1980 and reported in 1987. Groups of five female and five male mice were exposed to 100, 200, 400, 800 and 1600 ppm ethylene oxide for four h. No deaths were observed at 100, 200 and 400 ppm. 5/5 male mice and 4/5 female mice exposed to 800 ppm died 1-3 days after exposure. At 1600 ppm, all male (5/5) and female (5/5) mice died within 4 h after exposure. No clinical signs were described at 100-400 ppm. In the groups exposed to 800 ppm ethylene oxide, lacrimation and dyspnoea were observed. The clinical findings reported at the highest dose included severe dyspnoea, incoordination, semi-consciousness and diarrhoea. The lowest LC50 value was 660 ppm (95% CI 509-856 ppm) as calculated for female mice. This corresponds to 1189 mg/m3 air.

Ethylene oxide was tested on groups of rats both for a 4 -hour and a 1 -hour inhalation exposure, followed by 14 days of observation. Groups of five Sprague-Dawley rats/sex were exposed, and clinical signs and mortality was recorded. Clinical signs noted included irregular breathing, absence of certain reflexes, and tremors. Rats that died had moderate to severe pulmonary congestion. The calculated LC50 values, reported as ppm by volume (with 95% confidence limits), were as follows.:Four-hour LC50 values were 1972 (1887 to 2061) ppm for males; 1537 (1391 to 1698) ppm for females; 1741 (1655 to 1831) ppm for the combined sexes. The 1 -hour LC50 values were 5748 (5276 to 6262) ppm for males; 4439 (4034 to 4884) ppm for females; 5029 (4634 to 5459) ppm for the combined sexes (Snellings et al., 2011).

Effects of 4-h vapour exposure on ten male rats was performed using concentrations of 2298, 1992, 1843, 1648, 1343, 882 ppm (= 4140, 3590, 3320, 2970, 2420, 1590 mg/m³). Control animals were included in the study. At the two highest doses (2298 and 1992 ppm), all animals died, hence the mortality rate was 100%. For the two mid-concentrations (1843 and 1648 ppm), mortality was 90 and 40%, respectively. The two lowest concentrations resulted in a mortality rate of 20% (1343 and 882 ppm). Clinical signs were also reported, such as diarrhea, gasping, and occasionally salivation. The greatest respiratory effect of the agent in rats appeared to be that due to simple irritation in the upper respiratory passages. The LC50 was reported to be 2.63 mg/l (Jacobson et al., 1955).

A simple method is presented for estimating a non-lethal level for inhalation toxicity studies. By reviewing 209 LC50 studies representing 96 chemicals that also reported a non-lethal level, it has been shown that taking 1/3 of the LC50 is a conservative estimate for a non-lethal exposure level. This approach was also compared to studies with LC01 and BMCL05 calculations. In the 38 studies that reported either of these values, again taking 1/3 of the LC50 provided a more conservation estimate for the non-lethal threshold. The studies included time intervals from 5 min out to 8 h and utilized multiple species such as the rat, mouse, hamster, guinea pig and dog. In all but 13 cases, taking 1/3 of the LC50 provided a more conservative estimate for a non-lethal exposure level compared to the experimentally observed value. In all but one of the 13 cases, the higher values were consequences of the selection of the exposure levels (Rusch et al., 2009).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The overall experimental test data are in sum reliable and suitable for classification purposes under Regulation 1272/2008. As a result, the substance is classified with acute oral toxicity category 3 (H301 toxic if swallowed) and acute inhalation toxicity category 3 (H331: toxic if inhaled).

In addition, ethylene oxide requires classification with STOT SE category 3 (H335 May cause respiratory irritation and H336 May cause drowsiness and dizziness)