Reaction mass of 2-methylpent-2-ene and diisopropyl ether

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 03, 2010 - June 18, 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP with certificate; OECD guidance; no deviation to the study plan

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(propan-2-yloxy)propane; 2-methylpent-2-ene

EC Number:

906-484-8

Molecular formula:

Not applicable as multiconstituent substance.

IUPAC Name:

2-(propan-2-yloxy)propane; 2-methylpent-2-ene

Details on test material:

- Lot/batch No.: 10013591
- Expiration date of the lot/batch: March 2011
- Storage condition of test material: In refrigerator at 2-8 ºC, under inert gas, away from light

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Species / Strain: Rat, CRL (WI) BR of Wistar origin
Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90.
Hygienic level: SPF at arrival and kept in good conventional environment during the study.
Age of animals at arrival: Young adult rats, 7-9 weeks old
Body weight range at treatment: Male: 327-334 g; Female: 194-207 g
Number of animals: 5 male and 5 female (nulliparous and non pregnant animals) rats
Number of animals/group: 5 animals/ sex
Acclimatisation time: 21 days
Acclimatisation to the test apparatus: 17 days
- Fasting period before study: no
- Housing: Group caging (2 or 3 animals, by sex, per cage)
- Diet (e.g. ad libitum): The animals received ssniff® SM R/M-Z+H complete diet produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum.
- Water (e.g. ad libitum): Animal received tap water from watering bottles. The drinking water is periodically analysed and is considered not to contain any contaminants

Environmental conditions:
Illumination: Artificial light, from 6 a.m. to 6 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: 8-12 air exchanges/hour by central air-condition system.
Environmental conditions were maintained by an air-condition system. Temperature and relative humidity were verified and recorded daily during the study.

Administration / exposure

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: anodised aluminium Flow Past Exposure Chamber (CR Equipment SA, Switzerland)
- Exposure chamber volume: 6 L
- Method of holding animals in test chamber: polycarbonate restraining tubes
- Source and rate of air: rate: Source: no data; 1.0 L/min
- Method of conditioning air: The air was supplied by an oil-free air compressor and was filtered in a two-stage filter set (Festo: 1μm and 0.01 μm). The temperature of the air was regulated by a heat exchanger. The air was not humidified in order to avoid modification of particle size distribution.
- System of generating particulates/aerosols: The test atmosphere was generated by a compressed air nebulizer (TSE Systems GmbH, Bad Homburg, Germany.) In the nebulizer the air flow rate was 15 L/min.
- Method of particle size determination: 7-stage cascade impactor type 02-150 (IN-TOX Products, N.M., USA)
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: 23.8-26.3 °C; 26.5-9.1 % relative humidity; pressure: no data

TEST ATMOSPHERE
- Brief description of analytical method used: The actual test atmosphere concentration was measured five times during exposure by pulling a volume of 10 L of test atmosphere (flow rate: 2.0 L/min) through sampling cylinders (length: 100mm, dia. 30mm) tightly filled with about 20g of granulated activated carbon (Reanal Private Ltd., Prod. No. 29903-1-99-33, pellet diameter 4mm). The amount of adsorbed test item was determined gravimetrically by the balance type Mettler PM100 (d = 1mg).
- Samples taken from breathing zone: yes

VEHICLE
no vehicle used

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see any other information on materials and methods
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
MMAD: Mass Median Aerodynamic Diameter (mean): 0.59 μm
GSD: Geometric Standard Deviation (mean): 1.35
Inhalable Fraction: Aerodyn. Diameter < 4μm: 100 %

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: upper limit of the classification into acute toxicity category 4 according to the CLP-regulation.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

method see above

Duration of exposure:

4 h

Remarks on duration:

nose-only exposure

Concentrations:

22.9 mg/L (Mean Achieved Concentration)

No. of animals per sex per dose:

5 Males, 5 Females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Animals were checked twice daily during the observation period for morbidity and/or mortality.
All animals were observed for clinical signs at 1st, 2nd and 3rd hours during exposure, as soon as practicable following removal from restraint, one hour after exposure and subsequently once daily for fourteen days.
Individual bodyweights were recorded on the day of exposure Day 0 (prior to exposure) and Days 1, 3, 7 and 14.

- Necropsy of survivors performed: yes; At the end of the fourteen day observation period, the animals were euthanized by exsanguination under anaesthesia (intra-peritoneal injection of Euthasol® 40%) and gross necropsies were performed. These included a detailed examination of the abdominal and thoracic cavities with special attention given to the respiratory tract for macroscopic signs of irritancy or local toxicity.

- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 22.9 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There was no died animal during the study.

Clinical signs:

other: All male and female animals were symptom-free during the day of treatment and observation period. Only in one animal was found any porphyrin discharge around the left eye during the treatment period. This animal became symptom-free one hour after exposure

Body weight:

On basis of body weight and body weight gain data, there was no notable test item effect observable in the exposed animals.

Gross pathology:

A single four hours nose-only exposure of reaction mass of DIPE and 2-methylpent-2-ene to CRL: (WI) BR rat followed by a 14-day observation period at a dose level 20 mg/L was not associated with any test item-related macroscopic findings.

Any other information on results incl. tables

Individual Body weight data:

Sex	Animal Number	Body weight (g)					Weekly Increase (g)
		Day 0	Day 1	Day 3	Day 7	Day 14	Week 1	Week 2
Male	5878	329	331	336	363	405	34	42
	5879	329	330	333	362	406	33	44
	5880	327	334	340	366	415	39	49
	5885	334	328	336	364	410	30	46
	5886	327	324	334	361	398	34	37
Mean:		329.2	329.4	335.8	363.2	406.8	34	43.6
*Difference in %			0.1	1.9	8.2	12.0	10.3	12.0
Female	5906	202	206	207	218	239	16	21
	5908	194	202	206	220	228	26	8
	5910	207	204	210	224	237	17	13
	5920	205	202	210	222	238	17	16
	5923	202	200	207	230	240	28	10
Mean:		202.0	202.8	208.0	222.8	236.4	20.8	13.6
*Difference in %			0.4	2.6	7.1	6.1	17.0	6.1

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LC50 inhalation, rat, for gases or vapours is >20 mg/litre/4h. Consequently, Reaction mass of 2-methylpent-2-ene and diisopropyl ether must not be classified for acute toxicity-inhalation.

Executive summary:

Under the experimental conditions of this study, no deaths occurred in a group of ten rats exposed to a mean achieved test item concentration of 22.9 mg/L for four hours. The acute inhalation median lethal concentration (4hr LC₅₀) of test itemreaction mass of DIPE and 2-methylpent-2-ene, in Wistar Crl:(WI) BR rats, was therefore considered to be greater than 22.9 mg/L.