Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
May 12th, 2010 - May 26th, 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance methyl laurate (CAS NO. 111-82-0). In accordance 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)
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
- CAS No. of test material (as cited in study report): 111-82-0
- 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 Februray
- Storage condition of test material: At room temperature in the dark under nitrogen

Test animals

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 9-11 weeks old
- Weight at study initiation: weight variation did not exceed ± 20% of the sex mean
- Fasting period before study:
- Housing: Before exposure-Group housing of maximally 5 animals per sex per cage in labeled Makrolon cages (type IV; height 18cm.) 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 - Group housing as described above, maximally 3 animals per sex per cage.
- Diet : Free access to pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäteb GmbH, Soest, Germany).
- Water : Free access to tap-water except during exposure to the test substance.
- Acclimation period: 5 days before the start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3°C
- Humidity (%): 40-70%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/ 12 hour dark cycle.

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 each 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.

TEST ATMOSPHERE
- Brief description of analytical method used: The actual concentration was determined ten times during the exposure period. Samples were drawn from the test atmosphere 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).
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
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 ten times during the exposure period. Samples were drawn from the test atmosphere through a tube mounted in one of the free animal ports of the middle section of the exposure chamber. Opacity monitoring showed that
Duration of exposure:
4 h
Concentrations:
The mean actual concentration was 5.6 ± 0.5 mg/L. The nominal concentration was 7.1 mg/L.

No. of animals per sex per dose:
3 males and 3 females (females were nulliparous and non-pregnant) per exposure level
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: mortality: twice daily, clinical signs during exposure, twice on day of exposure and daily thereafter.
- Frequency of weighing: Days 1 (pre-administration), 2, 4, 8 and 15.
- Necropsy of survivors performed: yes

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
Clinical signs:
other: 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.

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:
Based on these results methyl laurate does not have to be classified and has no obligatory labeling requirement for acute inhalation toxicity according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.