Diisopentyl ether

Endpoint summary

Description of key information

The substance showed no acute oral toxicity in female rats with an LD50 of > 2000 mg/kg bw. In an acute inhalation study, the LC50 was determined at 2-10 mg/L for male and female rats.

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

Study period:

2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Janvier (53940 Le Genest St Isle - France)
- Age at study initiation: 8 weeks old
- Weight at study initiation: 191 - 205 g
- Housing: group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid containing sawdust bedding
- Diet (e.g. ad libitum): free access to standard diet (M20, SDS).
- Water (e.g. ad libitum): free access to tap water.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h/12h
- Air changes (per hr): approx. 15 changes per hour

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test item was administered as supplied by gavage under a volume of 2.57 mL/kg body weight (corresponding to 2 g/kg bw, according to the calculated density).

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

six females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed daily for a period of 14 days to identify any behavioural or toxic effects. The rats were weighed on day 0 (just before administering the test item) and at 2, 7 and 14 days after dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Preliminary study:

Not applicable

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No clinical signs related to the administration of the test item were observed.

Gross pathology:

Macroscopical examination of the animals at the end of the study did not reveal treatment related changes.

Other findings:

Not applicable.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of diisopentyl ether is higher than 2000 mg/kg body weight by oral route in the rat. In accordance with the OECD guideline No. 423, the LD50 cut-off of the test item may be considered as 5000 mg/kg body weight by oral route in the rat.

Executive summary:

In a GLP compliant acute oral toxicity study, performed according to OECD guideline 423, the test item diisopenyl ether was administered to a group of 6 female Sprague Dawley rats at the single dose of 2000 mg/kg body weight.

No mortality occurred during the study. No clinical signs related to the administration of the test item were observed. The body weight evolution of the animals remained normaly throughout the study. The macroscopical examination of the animals at the end of the study did not reveal treatment related changes.

In conclusion, the LD50 of diisopentyl ether is higher than 2000 mg/kg body weight by oral route in the rat. In accordance with the OECD guideline No. 423, the LD50 cut-off of the test item may be considered as 5000 mg/kg body weight by oral route in the rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Value:

mg/kg bw

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:

2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 12 weeks old
- Weight at study initiation: 197-225 (females); 331-371 (males)
- Housing: group housing of 5 aminals per sex per cage in Makrolon cages (type IV; height 18 cm) containing sterilised sawdust as bedding material (Litalabo, France) and paper as cage-enrichment.
- Diet (e.g. ad libitum): free access to pelleted rodent diet (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water (e.g. ad libitum): free access to tap water.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12h/12h
- Air changes (per hr): approx. 15 changes per hour

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: nose-only exposure units. The chamber consisted of three animal sections with eight animal ports each. Each animal port had its own atmosphere inlet and exhaust outlet.
- Method of holding animals in test chamber: plastic animal holders, positioned radially through the outer cylinder around the central column
- Source of air: compressed air
- System of generating particulates/aerosols: a vapor was generated by nebulization of the test substance. For 2 mg/L, a LC SPRINT STAR nebulizer (Pari, Starnberg, Germany) was used, dried pressurized air was used for dilution (main total airflow 21 L/min). For 10 mg/L, a type 950 nebulizer (Hospitak Inc., Lindenhurst, NY, USA) was used, humidified pressurized air was used for dilution (mean total airflow 19 L/min.).
- Method of particle size determination: Not applicable.
- Treatment of exhaust air: exhaust air is passed through a filter before it was released to the exhaust of the fume hood.
- Temperature, humidity, pressure in air chamber: 21-22°C; 16-18% (exposure to 2 mg/L) and 49-50% (exposure to 10 mg/L).
TEST ATMOSPHERE
- Brief description of analytical method used: The actual concentration was determined continuously during each exposure. A small stream of the test atmosphere was drawn through a tube mounted in one of the free animal ports. The tube was heated to avoid condensation of the test atmosphere. The tube was connected to a gas cell which was mounted in a FTIR spectrophotometer. The mean values and the SD were calculated.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Target: 2 and 10 mg/L
Nominal: 1.8 and 6.7 mg/L
Analytical: 1.9 (± 0.15), 7.1 (± 1.8)
Remark: Due to a technical failure of the FTIR, the exposure was interrupted for approx. 20 minutes. The generation time was elongated to compensate for this interruption and to achieve an actual exposure time of 4 hours. Following this interruption, it was technically not possible to meet the target concentration of 10 mg/L.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Frequency of observations and weighing: The animals were inspected twice daily for mortality throughout the test. During exposure, the animals were observed three times for mortality, behavioural signs of distress and effects on respiration. After exposure, animals were checked one and three hours after exposure and once daily thereafter until Day 15. The body weight of each animal was recorded on Days 1 ( just prior to exposure), 2, 4, 8 and 15 and at death (if found dead or sacrificed after Day 1).
- Necropsy of survivors performed: Yes. Particular attention was given to any changes in the respiratory tract.

Preliminary study:

Not applicable.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.9 - 7.1 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

At 2 mg/L, no mortality occurred. At 7 mg/L, one male was found dead and the remaining two males were sacrificed for human reasons on Day 1 post-exposure. Two females were found dead on Day 2 and one female survived the observation period of 14 days.

Clinical signs:

other: At 2 mg/L, no clinical signs were noted during and after exposure. At 7 mg/L, slow breathing was noted in two males and one female during exposure. After exposure, hunched posture, laboured respiration and piloerection were seen in all animals on Day 1.

Body weight:

Overall body weight gain in males and females exposed to 2 mg/L was within the range expected for rats of this strain and age used in this type of study. Body weight loss was seen in the surviving female of the study period following exposure to 7 mg/L.

Gross pathology:

Macroscopic post mortem examination of the animals that were found dead or sacrificed for ethical reasons during the study revealed abnormalities at the lungs (dark red discolouration). No abnormalities were found at macroscopic examination of the surviving animals.

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The inhalatory LC50 (4 h) value of diisopentyl ether in Wistar rats was established to be within the range of 1.9 and 7.1 mg/L. Based on these results, the inhalatory LC50 (4h) value of diisopentyl ether in Wistar rats was considered to fall within the range of 2 - 10 mg/L.

Executive summary:

In a GLP compliant study, performed according to OECD guideline 436, the acute inhalation toxicity of Diisopentyl ether was investigated. Diisopentyl ether was administered as a vapor by inhalation for 4 hours to two groups of three male and three female Wistar rats. At 2 mg/L, no mortality occurred. At 7 mg/L, one male was found dead and the remaining two males were sacrificed for human reasons on Day 1 post-exposure. Two females were found dead on Day 2 and one female survived the observation period of 14 days. The inhalatory LC50 (4 h) value of diisopentyl ether in Wistar rats was established to be within the range of 1.9 and 7.1 mg/L. Based on these results, the inhalatory LC50 (4h) value of diisopentyl ether in Wistar rats was considered to fall within the range of 2 - 10 mg/L.

Endpoint conclusion

Dose descriptor:

LC50

Value:

7 000 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral route

In a GLP compliant acute oral toxicity study, performed according to OECD guideline 423, 6 female rats were exposed to 2000 mg/kg bw of Diisopentyl ether (Phycher, 2011). No mortality occurred during the study. No clinical signs related to the administration of the test item were observed. The body weight evolution of the animals remained normaly throughout the study. The macroscopical examination of the animals at the end of the study did not reveal treatment related changes. In conclusion, the LD50 of diisopentyl ether is higher than 2000 mg/kg body weight by oral route in the rat.

Inhalation route

In an acute inhalation study performed according to OECD guideline 436 and GLP guidelines, diisopentyl ether was administered as a vapor by inhalation for 4 hours to two groups of three male and three female Wistar rats. Animals were observed daily and body weight measurements were taken on Days 1, 2, 4, 8 and 15. Macroscopic examination was performed on the day of death or after terminal sacrifice (day 15).

At 2 mg/L, no mortality occurred. At 7 mg/L, one male was found dead and the remaining two males were sacrificed for human reasons on Day 1 post-exposure. Two females were found dead on Day 2 and one female survived the observation period of 14 days. Based on these results, the inhalatory LC50 (4h) value of diisopentyl ether in Wistar rats was considered to fall within the range of 2 - 10 mg/L.

Dermal route In accordance with column 2 of REACH Annex VIII-IX, as acute toxicity studies for the oral and inhalation route are available, no study regarding the dermal route is needed.

Justification for classification or non-classification

As no mortality was observed after administration of a single dose of 2000 mg/kg bw, Diisopentyl ether does not have to be classified for acute oral toxicity.

According to Directive 67/48/EEC, Diisopentyl ether has to be classified as Xn; R20 (Harmful if inhaled) based on the acute inhalation LC50 value of 2 - 10 mg/L. Based on the same data, the substance has to be classified for Acute toxicity, Cat. 3, via inhalation route (H331, Toxic if inhaled) according to the EU Classification, Labeling and Packaging of Substance and Mixtures (CLP) Regulation (EC) No. 1272/2008