2-Butyne-1,4-diol, polymer with 2-(chloromethyl)oxirane, brominated, dehydrochlorinated, methoxylated

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, no restrictions, fully adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-Butyne-1,4-diol, polymer with 2-(chloromethyl)oxirane, brominated, dehydrochlorinated, methoxylated

EC Number:

614-503-3

Cas Number:

68441-62-3

Molecular formula:

(C3H7O2)xC4H4O2Br2(C4H9O2)y with x + y = 2.5

IUPAC Name:

2-Butyne-1,4-diol, polymer with 2-(chloromethyl)oxirane, brominated, dehydrochlorinated, methoxylated

Constituent 2

Reference substance name:

Triethyl phosphate

EC Number:

201-114-5

EC Name:

Triethyl phosphate

Cas Number:

78-40-0

Molecular formula:

C6H15O4P

IUPAC Name:

triethyl phosphate

Test material form:

liquid: viscous

Details on test material:

- Name of test material (as cited in study report): IXOL B251
- Chemical name: Halogenated Polyether Polyol
- Other name: Polyol IXOL B251
- Composition of carrier: 6.5% Triethylphosphate in B350
- Molecular formula: [CH2OH-CHOH-CH2-]x-O-CH2CBr=CBrCH2-O-[-CH2-CHOH-CH2-OCH3]y with 45% primary OH and 55% secondary OH
- Analytical purity: >99%
- Lot/batch No.: 9262
- Physical state: a dark brown liquid
- Storage conditions: ambient temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories.
- Age at study initiation: 6 weeks
- Weight (average) at study initiation: males 210.4 gram, females 149.4 gram
- Housing: five per cage/per sex
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-65
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

The animals were exposed to the test atmosphere in a nose-only inhalation chamber, a modification of the chamber manufactured by ADG Developments Ltd., Codicote Hitchin, Hets, SG4 8UB, United Kingdom (see Figure 1). The inhalation chamber consisted of a cylindrical stainless steel column, surrounded by a transparent cylinder. The column had a volume of ca. 50 liters and consisted of a top assembly with the entrance of the unit, a rodent tube section and at the bottom the base assembly with the exhaust port. The rodent tube section had 20 ports for animal exposure. Several empty ports were used for test atmosphere sampling, measurement of oxygen concentrations, temperature and relative humidity. The animals were secured in plastic animal holders (Battelle), positioned radially through the outer cylinder around the central column. Male and female animals were placed in alternating order. The remaining ports were closed. Only the nose of the rats protruded into the interior of the column.

The inhalation equipment was designed to expose the animals to a continuous supply of fresh test atmosphere. To generate the test atmosphere, the test material was diluted with water (80% test material/20% water) and a controlled amount of the solution (controlled by a peristaltic pump; Minipulse, Gilson, Velliers le Bel, France) was nebulized with an air-driven atomizer (Schlick type 970/S, Coburg, Germany). The atomizer was supplied with humidified compressed air, the flow of which was measured using a mass stream meter (Bronkhorst Hi Tec, Ruurlo, The Netherlands). The resulting test atmosphere was led to the top inlet of the exposure chamber and from there to the noses of the animals and exhausted at the bottom.

During the generation of the test atmosphere, the readings of the mass stream meter and the settings of the pump were recorded at regular intervals (approximately each half hour). The airflow through the exposure unit during exposure was 40.3 nL/minute , in which nL stands for normal liter, the volume at 273 K and 1013 Pa. The animals were placed in the exposure unit after stabilization of the test atmosphere. The period between the start of the test atmosphere generation and the start of exposure of the animals was 40 minutes.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The actual concentration (by weight) of non-volatile particles present in the test atmosphere was determined approximately once each hour by means of gravimetric analysis.

Duration of exposure:

4 h

Concentrations:

The actual concentration during exposure was 5.47 ± 0.05 g/m3. The nominal concentration was 21.1 g/m3, indicating a generation efficiency of 26%. The mass median aerodynamic diameter (MMAD) was 2.3 µm and the distribution of particle sizes had a geometric standard deviation (gsd) of 2.8.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

The study was started on 2 December 2009 with the exposure of 5 male and 5 female rats to a target concentration of at least 5 g/m3 IXOL B251 for 4 hours. The day of exposure was named day 0 of the study. Animals were kept for an observation period of 14 days. The study was finished with necropsy of the animals on 16 December 2009.

Clinical signs and mortality
The rats were visually inspected just before exposure, for reactions to treatment during the exposure, shortly after exposure, and at least once daily during the observation period.

Body weight
Body weight of the animals was recorded just prior to exposure (day 0) and on days 7 and 14.

Pathology
At the end of the observation period, the rats were sacrificed by exsanguination from the abdominal aorta under pentobarbital anaesthesia and examined for gross pathological changes.

Statistics:

not performed

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 470 mg/m³ air (analytical)

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: Animals did not show abnormalities during the first two hours of exposure. During the second two hours of exposure all animals showed breathing at a decreased rate.No clinical abnormalities were observed shortly after exposure or during the remainder of t

Body weight:

Body weight gain was as expected for animals of this age and strain.

Gross pathology:

No treatment-related macroscopic abnormalities were found at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The 4-hour LC50 of Polyol IXOL B251 was >5.47 g/m3 for male and female rats.

Executive summary:

The acute inhalation toxicity of Polyol IXOL B251 was investigated in a GLP compliant, OECD guideline 403 study in rats (TNO, 2010a). The actual concentration during exposure was 5.47 ± 0.05 g/m3. Body weight was measured just before exposure and weekly thereafter. At necropsy, animals were examined for gross pathological changes. The animals did not show abnormalities during the first two hours of exposure. During the second two hours of exposure all animals showed breathing at a decreased rate. No clinical abnormalities were observed shortly after exposure or during the remainder of the observation period. Body weight gain was as expected for animals of this age and strain. No treatment-related macroscopic abnormalities were found at necropsy. Mortality did not occur. It is therefore concluded that the 4-hour LC50 is above 5.47 g/m3 for male and female rats.