Zinc methacrylate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 June - 01 July 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 190-211 g
- Fasting period before study: Food was removed at Day 1 and then redistributed 4 h after the test item administration.
- Housing: Animals were housed by group of three in solid-bottomed clear polycarbonate cages with stainless steel mesh lids.
- Diet: Food, ad libitum
- Water: Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 41-70 %
- Air changes: At least ten changes per hour
- Photoperiod: 12 h dark / 12 h light

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

- 3 females/dose (2000 mg/kg bw)
- 6 females/dose (300 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day.
Bodyweight: The animals were weighed on Day 0 (just before administering the test item) then on Days 2, 7 and 14.
- Necropsy of survivors performed: Yes; On Day 14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels and macroscopic examination was performed.

Statistics:

None

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All animals were died at 2000 mg/kg bw. No mortality was observed at 300 mg/kg bw.

Mortality:

- All three treated rats were died at 2000 mg/kg bw between 3 and 6 h after the test item administration.
- No mortality was observed at 300 mg/kg bw.

Clinical signs:

other: other: other: other: - At 2000 mg/kg bw, mortalities were preceded by a decrease of the spontaneous activity (3/3) associated with a decrease of muscle tone (2/2), a decrease or an absence of Preyer's and righting reflex (3/3) and a piloerection (2/2). -

Gross pathology:

- Macroscopical examination of the animals treated at 2000 mg/kg bw which died during the test revealed a white thickening layer at the level of the corpus.
- No macroscopic abnormalities were observed at 300 mg/kg bw.

Other findings:

None

None

Interpretation of results:

other: Category 4 based on EU CLP criteria

Conclusions:

Under the test conditions, the oral LD50 for ZnDMA was 500 mg/kg bw in female rats.

Executive summary:

In an acute oral toxicity study performed according to OECD Guideline 423 and in compliance with GLP, groups of Sprague Dawley rats were given a single oral (gavage) dose of the test substance at 2000 mg/kg bw (3 females) followed by 300 mg/kg bw (6 females). Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination. All three treated rats were died at 2000 mg/kg bw between 3 and 6 h after the test item administration. No mortality was observed at 300 mg/kg bw. At 2000 mg/kg bw, mortalities were preceded by a decrease of the spontaneous activity (3/3) associated with a decrease of muscle tone (2/2), a decrease or an absence of Preyer's and righting reflex (3/3) and a piloerection (2/2). At 300 mg/kg bw, from 30 minutes after the test item administration, a decrease of the spontaneous activity (6/6) associated with a decrease of righting reflex (5/6) and a piloerection (5/6). The animals recovered a normal activity between the 3rd and the 4th day of the test. Body weight evolution of the animals remained normal throughout the study. Macroscopical examination of the animals treated at 2000 mg/kg bw which died during the test revealed a white thickening layer at the level of the corpus. No macroscopic abnormalities were observed at 300 mg/kg bw. In this study, the oral LD50 of test substance was considered to be 500 mg/kg bw in female rats. Under the test conditions, the oral LD50 was determined to be 500 mg/kg bw in rats (Seguier, 2008).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

ca. 500 mg/kg bw

Quality of whole database:

GLP and OECD guideline-compliant study with Klimisch score 1

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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:

guideline study

Remarks:

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

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

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

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:

ca. 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

Preliminary study:

Not applicable

Key result

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

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

Interpretation of results:

other: Not classified

Conclusions:

Under the test conditions, the inhalation LC50 for Zinc dimethacrylate was higher than 5.32 mg/mL for 4 h in rats.

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 the test substance 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. Under the test conditions, the inhalation LC50 of the test substance was determined to be greater than 5.32 mg/mL (equivalent to 5320 mg/m3) for 4 h in rats (Griffiths, 2013). 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

ca. 5 320 mg/m³ air

Quality of whole database:

GLP and OECD guideline-compliant study with Klimisch score 1

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral

In an acute oral toxicity study performed according to OECD Guideline 423 and in compliance with GLP, groups of Sprague Dawley rats were given a single oral (gavage) dose of the test substance at 2000 mg/kg bw (3 females) followed by 300 mg/kg bw (6 females). Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination. All three treated rats were died at 2000 mg/kg bw between 3 and 6 h after the test item administration. No mortality was observed at 300 mg/kg bw. At 2000 mg/kg bw, mortalities were preceded by a decrease of the spontaneous activity (3/3) associated with a decrease of muscle tone (2/2), a decrease or an absence of Preyer's and righting reflex (3/3) and a piloerection (2/2). At 300 mg/kg bw, from 30 minutes after the test item administration, a decrease of the spontaneous activity (6/6) associated with a decrease of righting reflex (5/6) and a piloerection (5/6). The animals recovered a normal activity between the 3rd and the 4th day of the test. Body weight evolution of the animals remained normal throughout the study. Macroscopical examination of the animals treated at 2000 mg/kg bw which died during the test revealed a white thickening layer at the level of the corpus. No macroscopic abnormalities were observed at 300 mg/kg bw. In this study, the oral LD50 of test substance was considered to be 500 mg/kg bw in female rats. Under the test conditions, the oral LD50 was determined to be 500 mg/kg bw in rats (Seguier, 2008).

Inhalation

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 the test substance 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. Under the test conditions, the inhalation LC50 of the test substance was determined to be greater than 5.32 mg/mL (equivalent to 5320 mg/m3) for 4 h in rats (Griffiths, 2013).

Justification for classification or non-classification

Based on the acute oral and acute inhalation toxicity studies on the substance, a classification of Acute Tox 4 (H302: harmful if swallowed) is warranted according to the EU CLP Regulation (EC) No 1272/2008 criteria.