Hydroxy(2-methylprop-2-enoato-O)zinc

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

09-31 October 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to OECD 436 Guideline with deviation: one sample was greater than 20 % of the mean achieved atmosphere concentration.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

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

Test material information

Constituent 1

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 a GLP-compliant 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).