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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993-02-23 till 1999-07-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

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:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl undec-10-enoate
EC Number:
203-910-8
EC Name:
Methyl undec-10-enoate
Cas Number:
111-81-9
Molecular formula:
C12H22O2
IUPAC Name:
methyl undec-10-enoate
Details on test material:
- Name of test material (as cited in study report): methyl undecylenate
- Substance type: organic
- Physical state: light yellow liquid
- Analytical purity: 98 %
- Purity test date: no data
- Lot/batch No.: 92-1004
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: in the dark a t room temperature
- Other:

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Wiga, Sulzfeld , FRG
- Age at study initiation: no data
- Weight at study initiation: Just before the start of the respective exposures, the mean body weights of the male and female rats were 246 g and 181 g, respectively .
- Fasting period before study: no data
- Housing: 5 by sex per cage.
- Diet (e.g. ad libitum): Institute's stock diet for rats ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: Total duration of the acclimatization period (including quarantaine ) was 21 (group A ) , 9 (group B ) , 10 (group C ) or 14 days (group D


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):


IN-LIFE DATES: From: 1993-02-02 (gropu A) 1993-03-31 (groups B, C, D) To: 1993-04-13

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Animals w ere exposed to the test atmosphere in a nose-only inhalation chamber which w as a modification of the chamber manufactured by ADG Developments LTD., Codicote, Hitchin, U.K.. The chamber consists of a cylindrical polypropylene column, surrounded by a transparent PVC cylinder. The polypropylene column had a volume of 50 liter, consisting of a top assembly with the entrance of the chamber, underneath the rodent tube section and at the bottom the base assembly with the exhaust port.
- Exposure chamber volume: the polypropylene column had a volume of 50 liter
- Method of holding animals in test chamber: The animals were secured in plastic animal holders (Battelle) , positioned radially through the outer cylinder around the central aluminium column.
- Source and rate of air: Before the start of the exposure, the rate of airflow through the generation device (see Section 2.4) was established at its pressure used. The pressure settings were recorded a t regular intervals (ca . each hour), and they did not change during the exposure period ( 1.0 bar ; 30 l / min ) .
- Method of conditioning air: The amount of humidified dilution air was recorded at the same time using calibrated rotameters. Bypass air was 24 (group A ) , 50 (group B ) , 30 (group C) and 32 l/min (group D) . In this way, the total exposure air flow was monitored indirectly through the aerosol generation system and was 54 (group A ) , 80 (group B ) , 60 (group C ) and 62 l/min (group D ).
- System of generating particulates/aerosols: Test atmospheres were generated by atomizing the test material into small droplets by using a compressed air driven nebulizer of the Institute's design. The nebulizer consisted of an atomizer and a glass jar, containing the test material. The atomizer coded DR 011, was purchased from Lechler (Germany). The nebulizer was operated a t a pressure of 1.0 bar. During operation, the test material was drawn through a sucktion pipe to the atomizer. The generated spray was blown against a baffle which was fitted approximately 8 cm below t h e nozzle
orifice to remove the larger droplets. The impacted test material was drained back into the test material supply at the bottom of the jar. The resulting aerosols were passed from the glass jar to the inlet of the exposure unit where it was diluted with humidified pressurized air. From there the test atmosphere was directed downward through the mixing chambers towards the animal noses.
- Method of particle size determination: carried out once per exposure using an 11-stage cascade impactor
- Treatment of exhaust air: At the bottom of the unit the test atmosphere was exhausted
- Temperature, humidity, pressure in air chamber: temperature between 19.7 and 25.0 °C, relative humidity between 30 and 72 %, pressure 1.0 bar


TEST ATMOSPHERE
- Brief description of analytical method used:
- Gravimetrical analysis:
The actual concentration of methyl undecylenate in the test atmosphere was determined once per hour by means of gravimetric analysis. Representative samples were obtained by passing 10 l test atmosphere at ca. 5 l/min through fiber glass filters (Sartorius) . Before and after sampling each filter was weighed. The actual concentration was calculated by dividing the weight difference before and after sampling by the amount of air sampled.
- GC analysis
GC anallysis was additionally carried out t o determine the amount of methyl undecylenate in the test atmosphere. Representative samples were obtained by passing 5-8 l test atmosphere a t 0.75 l/min through one impinger filled with acetone (p.a.). In preliminary experiments it was shown that one
impinger was sufficient since no test material was observed in the second impinger which were connected in tandem. The content of each impinger was quantitatively t ransferred to 50 ml volumetric flasks. Each impinger and the sampling tube were rinsed with the solution; each rinsing was transferred to the volumetric flasks as well.
- Samples taken from breathing zone: yes


VEHICLE (no vehicle used)
- Composition of vehicle (if applicable):
- Concentration of test material in vehicle (if applicable):
- Justification of choice of vehicle:
- Lot/batch no. (if required):
- Purity:


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Particle size distributions are given i n Table 2 of the original study report. Particle size measurement showed that at least 95 % of the particles had an aerodynamic diameter between 1.0 and including 4.2 µm.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:
The study was started with one group of 5 rats per sex which was exposed nose-only for 4 hours at a target concentration of at least 5 g/m³. Since
all animals died at that concentration, three more groups were exposed. During the assay proper, nominal concentrations were 2.6, 3.7, 4.5 and 5.9 g/m³, resp.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
GC analysis
Duration of exposure:
ca. 4 h
Concentrations:
2.67, 3.72, 4.54 or 5.48 g/m³ (measured)
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were visually inspected just before exposure, for reactions to treatment during the exposure, shortly after exposure, and a t l e a s t once daily during the observation period. Body weights were recorded just prior to exposure (day 0) , on days 7 and 14 and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: All rats were autopsied and examined for gross pathological changes.
Statistics:
The statistical program used was based on Finney (Finney, D. J., Probit Analysis, Cambridge Univ. Press, 3rd. ed. 1971).

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 3.76 mg/L air (analytical)
95% CL:
>= 3.25 - <= 4.1
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
ca. 3.58 mg/L air (analytical)
95% CL:
>= 2.92 - <= 4.07
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
ca. 3.94 mg/L air (analytical)
95% CL:
>= 3.34 - <= 4.46
Exp. duration:
4 h
Mortality:
Several rats were found dead during the last hour of exposure, viz. all rats exposed to 5.48 g/m3 (group A), 4 of 5 males and 4 of 5 females exposed to 4.54 g/m3 (group C), and 3 of 5 males and 1 of 5 females exposed to 3.72 g/m3 (group D). In addition, one male exposed to 4.54 g/m3 and one female exposed to 3.72 g/m3 were found dead within two hours after exposure stop.
Clinical signs:
other: Irregular breathing was observed in all rats exposed to 2.67 g/m3 (group B) and 4.54 g/m3 (group C ) during the third hour of exposure, and in all rats exposed to 3.72 g/m3 (group D) during the second and third hour of exposure. Shallow breathing was seen
Body weight:
In surviving rats, no abnormalities in body weight gain were observed except in most female rats exposed to 2.67 g/m3 (group B) that showed only
marginal body weight gain during the second week of observation.
Gross pathology:
Animals that died during or shortly after exposure showed numerous abnormalities. Stiffly closed eyes were seen in several rats. Two male rats of each group exposed to 3.72, 4.54 or 5.48 g/m3 showed presence of white substance in the eye chamber of both eyes; one male and one female exposed to 5.48 g/m3 showed the same finding but in one eye chamber only. Upon autopsy, almost all rats showed dark and swollen livers and dark discoloured, occasionally blood-containing, lungs. In addition, upon removal of the organs (such as liver) in animals exposed to the highest concentration, much oedema was observed as confirmed by the presence of large amounts of fluid. Occasional findings consisted of swollen blood vessels in various organs such as stomach, caecum, intestines, testes and/or seminal vesicles.
At terminal sacrifice of the surviving rats 14 days after exposure, no abnormalities were observed.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: other: Guidance to Regulation (EC) No 1272/2008 on CLP of substances and mixtures
Conclusions:
For the combined male and female data, the 4-hour LC50 value was 3.76 g/m3 for test item methyl undecylenate. Acc. to the old EU classification and labelling system 67/548/ECC, the test item is classified as R20, Xn, harmful by inhalation. Acc. to the new GHS system, hazard class and category acute tox. inhal. 4 would apply, hazard statement "harmful if inhaled, hazard statement no. 318.
Executive summary:

The aim of the present study was to determine the 4 -hour LC50 of methyl undecylenate. Methyl undecylenate was studied by nose-only exposure of four groups of five males and five females rats each to test atmosphere containing 2.67, 3.72, 4.54, or 5.48 g methyl undecylenate per m3. Nominal concentrations were 2.6, 3.7, 4.5 and 5.9 g/m3, respectively. The 4 -hour LC50 value was calculated using the probit function, as described by Finney (1971). For the combined male and female data, the 4-hour LC50 value was 3.76 g/m3 with 95%-confidence limits of 3.25 and 4.10 g/m3. When separated for sexes, the 4 -hour LC50 values (and 95%-confidence limits ) were 3.58 (2.92 -4.07) and 3.94 (3.34-4.46) g/m3 for males and females, respectively, indicating higher, though statistically insignificantly, susceptibility to methyl undecylenate for male rats .

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