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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
12 May - 26 May 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP guideline study, tested with the source substance CAS 111-82-0. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Version / remarks:
adopted in 2009
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Methyl laurate
- Molecular formula : C13H26O2
- Molecular weight: 214.34
- Substance type: Clear colourless liquid
- Physical state:Liquid
- Analytical purity: 99.33%
- Lot/batch No.: SME02/1301/K
- Expiration date of the lot/batch: 01 February 2011
- Storage condition of test material: At room temperature in the dark under nitrogen

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain as cited in report: Crl:WI (Han) (outbred SPF-Quality)
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 9 - 11 weeks old
- Weight at study initiation: 276 g (males), 206 g (females)
- Housing: before exposure, 5 animals per sex per cage in labelled Makrolon cages (type IV; height 18 cm) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, UK). After exposure, 3 animals per sex per cage.
- Diet: free access to pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäten GmbH, Soest, Germany).
- Water: free access to tap-water except during exposure
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3
- Humidity (%): 40-70
- Air changes (per hr): 15
- 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:
The design of the exposure chamber is based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). The chamber consisted of three animal sections with eight animal ports each. Each animal port had its own atmosphere inlet and exhaust outlet. The animals were placed in restraining tubes and connected to the animal ports. The number of animal sections and number of open inlets were adapted to the air flow in such a way that at each animal port the theoretical air flow was at least 1 L/min, which ensures an adequate oxygen supply to the animals. The main inlet of the test atmosphere was located at the top section and the main outlet was located at the bottom section. The direction of the flow of the test atmosphere guaranteed a freshly generated atmosphere for each individual animal.
All components of the exposure chamber in contact with the test material were made of stainless steel, glass, rubber or plastic. To avoid exposure of the personnel and contamination of the laboratory the exposure chamber was placed in a fume hood, which maintained at a slight negative pressure.

- Method of holding animals in test chamber: restraining tubes
- Source and rate of air: at least 1L/min.

- System of generating particulates/aerosols:
An aerosol was generated by nebulization of the test substance by means of a nebulizer (type 950, Hospitak Inc., Lindenhurst, NY, USA). The primary aerosol was diluted with pressurized air and passed through a cyclone, allowing larger particles to settle, before it entered the exposure chamber. The mean total airflow was 43.8 L/min.

- Method of particle size determination:
The droplet size distribution was characterized twice during the exposure period. The samples were drawn (2 L/min) from the test atmosphere through a tube mounted in one of the free animal ports of the middle section of the exposure chamber. The samples were collected with an 8 stage Marple personal cascade impactor containing fibre glass filters (SKC 225-713, Glass fibre, SKC Omega Specialty Division, Chelmsford, MA, USA) and a fibre glass back-up filter (SEC-290-F1, Westech, Upper Stondon, Bedfordshire, England). Amounts of test substance collected were measured gravimetrically. Subsequently the Mass Median Aerodynamic Diameter (MMAD) and the Geometric Standard Deviation (GSD) were determined.

- Temperature, humidity, pressure in air chamber:
The temperature and relative humidity were measured with a humidity and temperature indicator. The temperature of the atmosphere was between 17.4 and 19.1 °C and relative humidity was between 23 and 25%. These conditions were considered appropriate for this relatively short 4 hours exposure duration.

DETERMINATION OF ACTUAL CONCENTRATION
Samples were drawn from the breathing zone through a tube mounted in one of the free animal ports of the middle section of the exposure chamber. Samples were drawn through a glass fibre filter (type APFC04700, Millipore, Billerica, MA, USA). The collected amount of the test substance in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter (type G 1.6, Actaris Meterfabriek B.V., Dordrecht, The Netherlands).

MMAD AND GSD
The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (GSD) were determined twice. The MMAD was 4.2 µm (GSD 1.8) and 3.6 µm (GSD 1.9).
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The actual concentration was determined 10 times during exposure. For details, see Details on inhalation exposure.
Duration of exposure:
4 h
Concentrations:
7.1 mg/L (nominal concentration)
5.6 ± 0.5 mg/L (actual concentration)

No. of animals per sex per dose:
3
Control animals:
other: no, as a concurrent negative (air) control group is not necessary according to OECD Guideline 436
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: animals were checked twice daily for mortality. They were examined for clinical signs during exposure, twice on day of exposure and once daily thereafter until test ending.
- Frequency of weighing: day 1 (pre-administration), 2, 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathology with particular attention given to changes in the respiratory tract.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the study period.
Clinical signs:
Lethargy, hunched posture and/or laboured respiration were noted among all animals at 1 hour after exposure, with hunched posture persisting until day 2 after exposure. No clinical signs were noted during exposure.
Body weight:
Body weight gain in males and females were within the range expected for rats of this strain and age used in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
The MMAD of 4.2 µm (GSD 1.8) and 3.6 µm (GSD 1.9) indicates that the aerosol is respirable.

Any other information on results incl. tables

Aerodynamic particle size distribution in the test atmosphere.

 

Start of generation of test atmosphere:

9:01

End of generation of test atmosphere:

13:02

Sampling speed (L/min):

2

 

measurement 1:

 

Stage

Cut point

m)

Mass sampled

(mg)

Relative mass

(%)

Cumulative mass

(% of total sampled)

1

21.0

0.000

0.00

100.00

2

15.0

0.050

0.62

99.38

3

10.0

0.470

5.82

93.56

4

6.0

1.430

17.70

75.87

5

3.5

3.390

41.96

33.91

6

2.0

2.430

30.07

3.84

7

0.9

0.200

2.48

1.36

8

0.5

0.110

1.36

0.00

Back up

0.25

0.000

0.00

0.00

 

 

MMAD (µm):

4.2

GSD:

1.8

 

 

Sampling time:

10:00

Sample volume (L):

2

 

measurement 2:

 

Stage

Cut point

m)

Mass sampled

(mg)

Relative mass

(%)

Cumulative mass

(% of total sampled)

1

21.0

0.000

0.00

100.00

2

15.0

0.000

0.00

100.00

3

10.0

0.530

5.56

94.44

4

6.0

1.570

16.47

77.96

5

3.5

3.480

36.52

41.45

6

2.0

3.030

31.79

9.65

7

0.9

0.440

4.62

5.04

8

0.5

0.390

4.09

0.94

Back up

0.25

0.090

0.94

0.00

 

 

MMAD (µm):

3.6

GSD:

1.9

 

 

Sampling time:

10:49

Sample volume (L):

2

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified