Glycerol, ethoxylated, esters with acrylic acid

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 Nov 2009 - 13 Oct 2010 (experimental)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study conducted in compliance with GLP regulations

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycerol, ethoxylated, esters with acrylic acid

EC Number:

500-322-6

EC Name:

Glycerol, ethoxylated, esters with acrylic acid

Cas Number:

144086-03-3

Molecular formula:

UVCB substance

IUPAC Name:

Glycerol, ethoxylated, esters with acrylic acid

Details on test material:

- Name of test material (as cited in study report): Glycerin 3EOTA
- Physical state: Liquid / colorless, clear
- Analytical purity: 98.9 g/100 g
- Analytical Report: 09L00272
- Lot/batch No.: GK 2656/104
- Expiration date of the lot/batch:
- Test substance No. (sponsor): 04/0114-3

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Wistar / RccHan:WIST(SPF)
- Source: Harlan Nederland, Kreuzelweg 53, NL-5961 NM Horst
- Age at study initiation: Young adult animals (male animals approx. 8 - 9 weeks, female animals approx. 10 – 11 weeks)
- Mean weight at study initiation: males: 262.44 g; females: 217.60 g
- Fasting period before study: no
- Housing: Single housing or up to 5 animals (caged in groups, if the animals were free from clinical signs and findings)
- Diet (ad libitum): Kliba-Labordiaet (Maus / Ratte Haltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland
- Water (ad libitum): Tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24
- Humidity (%): 30 – 70
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Two-component atomizer Mod. 970 (stainless steel, Schlick); Continuous infusion pump Perfusor (B. Braun)

- Exposure chamber: Head-nose inhalation system INA 20 (glass-steel construction, BASF SE, volume Volume ca. 55 L)

- Method of holding animals in test chamber: The animals were restrained in glass tubes and their snouts projected into the inhalation system.

- Source and rate of air:
- test group 1: Supply air flows (compressed air) plus dilution air (conditioned air) (from a central air-conditioning system): 1.5 m³/h;
Exhaust air flow: 2.7 m³/h
- test groups 2-3: Supply air flows (compressed air): 1.5 m³/h; Exhaust air flow: 1.35 m³/h

- Method of conditioning air: Central air conditioning system of the laboratory provides cold air of about 15°C. This cold air passes through an active coal filter, is tempered to room temperature of 20 to 24°C and passes through a second particle filter (H13 (HEPA) Camfil Farr, Germany). The so generated conditioned air is used to generate inhalation atmospheres.
Compressed air is produced by an oil-free compressor (HT 6, Josef Mehrer GmbH & Co KG, Germany). For this purpose, air is filtered by an inlet air strainer and introduced into the compressor. After passed through an second ultra filter (SMF 5/3, 108 mm, Donalson), the compressed air (15 bar) is stored in a storage of 1500 or 5000 L. The compressed air is conducted to the laboratories via pipes, where the pressure is reduced to 6 bar. In the laboratory, the compressed air can be taken as required.

- System of generating particulates/aerosols:
Liquid aerosols were generated: For each test group the aerosols were produced by continuously pumping amounts of the test substance (in case of test group 1 the test substance was continuously stirred) to a two-component atomizer. Using compressed air, the aerosol was produced with the atomizer inside the exposure system.

- Method of particle size determination:
Before sampling, the impactor stages were assembled with preweighed glass-fiber collecting discs, and equipped with a backup particle filter. The impactor was connected to the vacuum pump, and for each test group two samples were taken from the breathing zone of the animals. Sampling occurred 30 minutes (or later) after the beginning of the exposure. Volume of samples: 180 (test group 1), 60 (test group 2), and 30 L (test group 3).
After sampling the impactor was taken apart. The collecting discs and the backup particle filter were re-weighed.
The amounts of material adsorbed to the walls of the impactor and in the sampling probe (wall losses) were also determined quantitatively.

- Treatment of exhaust air: The exhaust air is filtered and conducted into the exhaust air of the building.

- Air changes: about 27 times per hour

- Temperature, humidity, pressure in air chamber: 20.5 - 22.4°C, 28.7 - 41.5%, 1.0 - 1.5 bar

TEST ATMOSPHERE
- Brief description of analytical method used:
- test group 1 and 2: gravimetric measurement
- test group 3: photometric analysis

- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
Test group / Sample / MMAD (μm) / Geometrical standard deviation:
1 1 2.5 1.9
1 2 2.7 1.9
2 1 3.5 2.2
2 2 3.3 1.8
3 1 3.1 1.6
3 2 2.0 2.6

- Test substance flow:
- test group 1: 0.659 mL/h
- test group 2: 3.4 mL/h
- test group 3: 13.8 mL/h

Analytical verification of test atmosphere concentrations:

yes

Remarks:

0.051 ± 0.002, 0.213 ± 0.027, 0.996 ± 0.107 mg/L

Duration of exposure:

4 h

Concentrations:

Nominal concentrations: 0.220 (test group 1), 2.267 (test group 2), and 9.20 mg/L (test group 3)
Analytical concentrations: 0.051 (test group 1), 0.213 (test group 2), and 0.996 mg/L (test group 3)

No. of animals per sex per dose:

Main test groups 1-3: 5 animals/sex/dose
Satellite test group 1: 3 male animals
Control group: one male animal

Control animals:

yes

Details on study design:

- Duration of observation period following administration: at least 14 days
- Frequency of observations and weighing:
- Body weights: Individual body weights once during the acclimatization period, shortly before exposure (day 0) and at least on days 1, 3 and 7, and before the sacrifice of the animals at the end of the observation period.
- Signs: Detailed clinical observations were recorded for each animal separately several times during exposure and at least once daily on the pre-exposure day and during the observation period.
- Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.
- Satellite group: organ weights (lungs), histopathology (all gross lesions, head, larynx (3 levels), pharynx, lungs, lymph nodes (tracheobronchial, mediastinal and mesenteric lymph nodes), nose (nasal cavity - 4 levels);

Statistics:

By the data the LC50 was calculated by Probit analysis (FINNEY, D.J. (1971): "Probit Analysis" Cambridge University Press) by means of a computer program.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.541 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: aerosol; deaths due to local irritation effects on respiratory tract

Mortality:

- Test group 1 (0.051 mg/L):
No lethality was observed in male and female animals during post exposure observation period.
- Test group 2 (0.213 mg/L):
One male and no female animal died after exposure on study day 1.
- Test group 3 (0.996 mg/L):
Three of five males and all of the female animals died during the exposure or after exposure on study day 0 or on study day 1 and 3.

Clinical signs:

other: - Test group 1 (0.051 mg/L): Nose discharge (colourless), abdominal respiration, accelerated respiration, piloerection. No clinical signs and findings were observed from study day 3 onward. - Test group 2 (0.213 mg/L): Distended abdomen, eye disc

Body weight:

- Test group 1 (0.051mg/L):
The mean body weights of the animals decreased during the first few post exposure observation days and increased from study day 3 onward.
- Test group 2 (0.213 mg/L):
The mean body weights of the animals decreased during the first few post exposure observation days and increased from study day 7 onward.
- Test group 3 (0.996 mg/L):
The mean body weights of the surviving male animals decreased during the first post exposure observation week but increased during the second week. However the body weight of the surviving male animals did not reach the initial level. No body weight data present by the female animals because all females died.

Gross pathology:

- Test groups 1-3 (main groups):
- Deceased animals:
In test group 2 (0.213 mg/L) a male rat that had died during the study period showed dark-red discoloration of the lung. In test group 3 (0.996 mg/L) 3 males and 5 females had died. From these animals only in 3 females there were abnormalities found at necropsy: several red foci in the lung, focal red discoloration of the lung, partly sunken surface of the lung, slight dilation with gaseous content of stomach and jejunum.
- Animals sacrificed at study termination:
In most animals the organs were without particular findings at necropsy. One male rat each in test group 2 and 3 showed few red foci in the pulmo sinister (lung).

Other findings:

- Test group 1 (0.051mg/L) (satellite group):
- Organ weights:
A minimal decrease in the absolute (98%) and relative lung (86%) weight in animals from the satellite group compared to the control group was considered to be not treatment-related.
- Gross lesions:
- Macroscopic findings: All animals without particular findings.
- Microscopic findings:
Histopathological examination revealed in the nasal cavity severe focal ulceration (3/3 animals at level I; 2/3 animals at level II) and/or inflammation (1/3 animals at level II) of squamous epithelium localized at the base of the nasal cavity. These findings were regarded as adverse and most likely the reason for lethality. Additionally, the larynx at level I showed slight epithelial alteration at the base of the epiglottis. This finding was regarded as non-adverse, but adaptive.

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU