Allyl (3-methylbutoxy)acetate

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 7 September, 2009

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Allyl (3-methylbutoxy)acetate

EC Number:

266-803-5

EC Name:

Allyl (3-methylbutoxy)acetate

Cas Number:

67634-00-8

Molecular formula:

C10H18O3

IUPAC Name:

allyl (3-methylbutoxy)acetate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: DMSO

Mass median aerodynamic diameter (MMAD):

>= 3.41 - <= 3.99 µm

Geometric standard deviation (GSD):

>= 1.93 - <= 2.42

Remark on MMAD/GSD:

Galai CIS-50 Aerosol Particle Size Analyser
Instrument: GALAI CIS-50 particle size analyzer
Manufactured by: Galai Pvt. Ltd., Israel
Principle of measurement: Laser based ‘Time-of-Transition Theory’
Unit of measurement: Aerosol particle size in µm.
Calibration: The instrument was calibrated once every three months using
the standards (Latex Microspheres - Thermo Labs, USA) to check the
performance efficiency and the performance of the instrument was within
the specified range of standards (1- 4 µm ).

Details on inhalation exposure:

The equipment, nose only exposure chamber is made of two stainless steel
cylindrical chambers with 24 exposure ports in 4 tiers (6 ports per tier) to
house up to 24 animals. Volume of the inhalation exposure chamber is 53
liters. The animal restrainers are made of polycarbonate tubes having
facility to trap the faeces for individual exposure tubes.
Inner chamber: Diameter 16 cm x Height 40 cm.
Outer chamber: Diameter 38 cm x Height 40 cm.
The equipment consists of two chambers, i.e. the aerosol inlet chamber and
the aerosol exhaust chamber. The chambers are cylindrical in shape and
placed one next to the other. The chamber has 24 ports into a central
plenum arranged as 4 horizontal rows centred on the sides of the cylindrical
chamber.
Animals are restrained in plexiglass exposure restrainers. The approximate
rat restrainer size for males: length 19.0 cm, diameter 6.0 cm and for
females: length 15.0 cm, diameter 6.0 cm.
These restrainers make an airtight seal with the plenum tube through a
rubber gasket. Within the plenum is a central tube into which the aerosol
enters at each port. Air flow carries the aerosol to the nose of the animals
restrained in position at the open ends of the tubes.
Aerosol not breathed and expired air pass into the plenum chamber (aerosol
exhaust chamber) and from there, via filters, to the exhaust system. The
plexiglass restrainers with the animals are housed in an outer chamber. This
chamber is made up of cylindrical plexiglass cover with an opening to fix
the restrainers to the central plenum. The chamber has temperature and
humidity control devices, and the temperature and the humidity where the
animals are housed is controlled and monitored.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

Based on the pre-study results, the following doses were selected for the main study.
G1 : Dimethyl sulphoxide with an injection rate of 0.4 mL/minute.
G2 : Test item concentration of 7% w/v in dimethyl sulphoxide with an injection rate of 0.4 mL/minute
G3 : Test item concentration of 10% w/v in dimethyl sulphoxide with an injection rate of 0.4 mL/minute
G4 : Test item concentration of 13% w/v in dimethyl sulphoxide with an injection rate of 0.4 mL/minute

No. of animals per sex per dose:

5 male and 5 female

Control animals:

yes

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 0.46 mg/L air

Based on:

test mat.

95% CL:

>= 0.414 - <= 0.517

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 0.5 mg/L air

Based on:

test mat.

95% CL:

>= 0.445 - <= 0.556

Exp. duration:

4 h

Effect levels 3

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

ca. 0.43 mg/L air

Based on:

test mat.

95% CL:

>= 0.386 - <= 0.482

Exp. duration:

4 h

Mortality:

G1: 0
G2: 2 ( 1 female and 1 male) on day 2.
G3: 5 ( 3 female and 2 male) on day 2.
G4: 3 ( 2 female and 1 male) on day 1
G4: 5 ( 2 female and 3 male) on day 2

Clinical signs:

other: The rats were observed for pre-terminal deaths four times during day 1 (at hourly intervals during the exposure) and twice after release of rats from the restrainers for clinical signs of toxicity / pre-terminal deaths and once daily during days 2-15. All

Body weight:

Body weights were recorded once during the acclimatization period and on day 1 (pre-exposure), 2, 4 (3 days post exposure), 8 (7 days post exposure) and 15 (14 days post exposure) and at death.
G1: The body weights of all the rats increased through the observation
period.
G2: The body weights of the all the surviving rats decreased on days 2, 4
when compared to their initial weight however all these rats gained weight
on day 8 and at terminal weighing .The pre-terminally dead rats showed
decrease in weight when compared to their initial weight.
G3 and G4: The body weight of the surviving rats decreased on days 2, 4, 8
when compared to their initial weight however rats gained weight at
terminal weighing. The pre-terminally dead rats showed decrease in weight
when compared to their initial weight.

Gross pathology:

Necropsy
At the end of the observation period, all surviving rats were euthanised using isoflurane anesthesia and subjected to detailed necropsy by an experienced prosector. The pre-terminally dead animals were also subjected to detailed necropsy.
G1: No abnormality was detected in any of the rats at necropsy.
G2 and G3: No abnormality was detected in the pre-terminally dead and
surviving rats at necropsy.
G4: Lung congestion was observed in pre-terminally dead rats (Rm9083,
Rm9086 and Rm9090). No abnormality was detected in rest of the preterminally dead and surviving rats at necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

LC 50 ( male /female) is : 0.46 mg/L of chamber air. It is classifed as H330 Category 2

Executive summary:

The acute inhalation toxicity study of Allyl Amyl Glycolate was conducted
in male and female Wistar rats with one vehicle control (G1) and three
treatment groups by nose only exposure using 7%, 10% and 13% w/v
aerosol of the test item in dimethylsulphoxide, to three groups of rats (G2,
G3 and G4) respectively. The aerosol was generated by a glass atomizer
with an injection rate of 0.4 mL/min, with 1.4 kg/cm2of atomizer pressure.
The rats housed in special rat restrainers were exposed to the test item
aerosol for four hours in an inhalation exposure chamber (dynamic state) for
the respective groups. The post-treatment observation period was 14 days.
The aerosol sampled from the inhalation chamber for particle
size analysis showed a mean aerosol particle size of 1.71 ± 1.18,
1.28 ± 1.05, 1.26 ± 0.99 and 1.31 ± 1.00 micrometers for G1, G2, G3 and
G4 groups respectively. The particle size was measured by using online
particle size analyser (Galai Particle size analyser) instead of normal
Cascade Impacter. So, the particle size is reported as Mean aerosol particle
size instead of Mass Median Aerodynamic Diameter (MMAD).
The generated aerosol particle distribution was uniform throughout the
exposure period of four hours. The geometric standard deviation (GSD)
value of the test item is 2.36, 2.22, 1.93 and 2.42 for G1, G2, G3 and G4
groups respectively, which were greater than 1.2, which indicates that the
aerosol is polydisperse. The fraction of aerosol with particle size of 3.99,
3.97, 3.41 and 3.91 micrometer is less than 95%, 97%, 97% and 97% in
G1,G2, G3 and G4 groups respectively this fraction is considered to be
inhalable up to the alveolar region of the lungs.
The analytically determined average concentrations of Allyl Amyl
Glycolate were 0.25, 0.47 and 0.84 mg per liter of chamber air for G2, G3
and G4 groups respectively.
Clinical signs like, clear nasal discharge, slight / moderate ataxia,
slight tremors/ moderate tremors, slight / moderate salivation, dyspnoea,
hypoactivity, and slight piloerection were observed in treated rats.
Pre-terminal death of 20%, 50% and 80% occurred in G2, G3 and G4 groups
respectively without sex preference. There was reduction in body weight
was observed in all surviving treatment group rats of G2 on days 2, 4 when
compared to their initial weight however all these rats gained weight on day
8 and at terminal weighing. There was reduction in body weight was
observed in all surviving treatment group rats of G3 and G4 on days 2, 4 and
8 when compared to their initial weight, however gained bodyweight at
terminal weighing when compared to the initial weight. The reduction in
body weight was observed in all pre-terminally dead rats.

As there were pre-terminal dead rats no abnormality and lung congestion
was detected. No abnormality was detected in any of the surviving rats
during necropsy.

LC 50 ( male /female) is : 0.46 mg/L of chamber air = 460 mg/m³ of air

LC 50 ( female) is : 0.43 mg/L of chamber air = 430 mg/m³ of air

LC 50 ( male) is : 0.5 mg/L of chamber air = 500 mg/m³ of air

It is classifed as H330 Category 2