Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09-31 October 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to OECD 436 Guideline with one deviation: one sample was greater than 20 % of the mean achieved atmosphere concentration.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Deviations:
yes
Remarks:
one sample was greater than 20 % of the mean achieved atmosphere concentration
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Zinc methacrylate
EC Number:
236-144-8
EC Name:
Zinc methacrylate
Cas Number:
13189-00-9
Molecular formula:
C4H6O2.1/2Zn
IUPAC Name:
zinc bis(2-methylacrylate)
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Zinc dimethacrylate
- Physical state: White powder
- Analytical purity: 95.3 % w/w
- Lot/batch No.: 1208152957
- Date of receipt: 04 October 2012
- Storage condition of test material: Room temperature in the dark

Test animals

Species:
rat
Strain:
other: RccHan : WIST strain
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Oxon, UK.
- Age at study initiation: Approximately 8-12 weeks
- Weight at study initiation: 200-350 g
- Housing: Animals were housed in groups of up to three by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes.
- Diet: Food (Harlan 2014C Rodent Diet, Harlan Laboratories UK Ltd, Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: 15/h
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany)
- Exposure chamber volume: Approximately 30 litres (dimensions: 28 cm diameter x 50 cm high)
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring.
- Source and rate of air: Compressed air at 60 L/min providing 120 air changes per hour.
- Method of particle size determination: Particle size of the generated atmosphere inside the exposure chamber was determined three times during the exposure period using a Marple Personal Cascade Impactor (Westech IS Ltd, Beds., UK).
- Treatment of exhaust air: The extract from the exposure chamber passed through a ‘scrubber’ trap and was connected with a high efficiency filter to a metered exhaust system.
- Temperature and humidity in air chamber: 19-20 ºC and 56-68 %; Temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter (Hanna Instruments Ltd, Beds., UK) located in a vacant port in the animals’ breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period.

TEST ATMOSPHERE
- Samples taken from breathing zone: Yes

VEHICLE
- In order to facilitate aerosolisation and reduce particle size, the test item was ground using a small amount of diethyl ether in a Retsch Planetary Ball Mill (Retsch (UK) Ltd, Leeds, UK) the solvent was removed via evaporation prior to use.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: See table 7.2.2/1
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.69 / 2.66
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5 mg/mL (target concentration)
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for up to 14 days.
- Frequency of weighing: Individual bodyweights were recorded on arrival, prior to treatment on the day of exposure and on Days 1, 3, 7 and 14 or at death.
- Necropsy of survivors performed: Yes, All animals, including the one that died during the study, were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.
Statistics:
None

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.32 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No mortality was observed in males and 1/3 female died during the study
Mortality:
No mortality was observed in males and 1/3 female died during the study.
Clinical signs:
other: - Upon removal from the chamber, all animals exhibited increased respiratory rate and ataxia and occasional instances of noisy respiration, which remained one hour post removal. - One day post exposure, all animals exhibited hunched posture, pilo-erection
Body weight:
- All animals exhibited bodyweight losses on the first day post-exposure.
- All animals exhibited bodyweight gains during the remainder of the recovery period, with the exception of one surviving female animal which showed no bodyweight gain from Days 1 to 3 post-exposure.
Gross pathology:
- No macroscopic abnormalities were detected at necropsy amongst the animals that survived until the end of the fourteen day recovery period.
- Macroscopic abnormalities such as dark patches in the lungs and gaseous distension in stomach were noted at necropsy in the animal that died during the course of the study.
Other findings:
None

Any other information on results incl. tables

Table 7.2.2/1: Particle Size Distribution

Cascade Impactor Data

Impactor Stage

Number

Cut Point

(μm)

Amount Collected (mg) per Sample Number

Mean Amount Collected (mg)

1

2

3

3

8.6

0.27

0.14

0.16

0.19

4

5.5

0.60

0.62

0.46

0.56

5

3.8

0.65

0.80

0.62

0.69

6

1.7

0.62

1.03

0.91

0.85

7

0.86

0.36

0.20

0.19

0.25

8

0.41

0.19

0.02

0.10

0.10

Back-up Filter

<0.41

0.22

0.23

0.23

0.23

Total Mean Amount of Test Item Collected

2.87

 

Calculation

Cut Point

(μm)

Log10

Cut Point

Mean Cumulative Amount Less Than Cut Point

mg

%

Probit

8.6

0.935

2.68

93.4

6.51

5.5

0.740

2.12

73.9

5.64

3.8

0.780

1.43

49.8

5.00

1.7

0.230

0.58

20.2

4.17

0.86

-0.066

0.33

11.5

3.80

0.41

-0.387

0.23

8.01

3.60

 

Results

 

Mean Mass Median Aerodynamic Diameter (MMAD) = 2.69 μm

Geometric Standard Deviation (GSD) = 2.66

Predicted amount less than 4 μm = 65.8%

 

Table 7.2.2/2: Mortality Data

Mean

Achieved

Atmosphere

Concentration

(mg/L)

Sex

Deaths

During

Exposure

Deaths

Post

Exposure

(1 Hour)

Deaths During Day of Observation

Total

Deaths

1

2

3

4

5

6

7

8-14

5.32

Male

0

0

0

0

0

0

0

0

0

0

1/6

Female

0

0

0

1

0

0

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the inhalation LC50 for Zinc dimethacrylate is higher than 5.32 mg/mL for 4 h in rats. It is therefore not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).
Executive summary:

In an acute inhalation toxicity study performed according to OECD Guideline 436, groups (3/sex/dose) of RccHan : WIST strain rats were exposed (nose only) to dust atmosphere of Zinc dimethacrylate at the concentration of 5.32 mg/mL (mean achieved) for 4 h. Animals were observed for mortality and signs of sensory irritation, airflow limitation and pulmonary irritation during the exposure period and continued the observation up to 14 days and necropsy was performed.

No mortality was observed in males and 1/3 female died on day 2. Common abnormalities noted during the study included increased respiratory rate, ataxia, hunched posture, pilo-erection, red/brown staining around the eyes and/or snout and wet fur. Frequent occurrences of sneezing and occasional instances of decreased respiratory rate and noisy respiration were also noted on the first days post exposure. The surviving animals recovered to appear normal from Days 8 to 9 post-exposure. All animals exhibited bodyweight losses on the first day post-exposure. All animals exhibited bodyweight gains during the remainder of the recovery period, with the exception of one surviving female animal which showed no bodyweight gain from Days 1 to 3 post-exposure. No macroscopic abnormalities were detected at necropsy amongst the animals that survived until the end of the 14 day recovery period. Macroscopic abnormalities such as dark patches in the lungs and gaseous distension in stomach were noted at necropsy in the animal that died during the course of the study. In this study, the combined inhalation LC50 of Zinc dimethacrylate was considered to be higher than 5.32 mg/mL for 4 h.

 

Under the test conditions, Zinc dimethacrylate inhalation LC50 is higher than 5.32 mg/mL for 4 h in rats, and is therefore not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).

Categories Display