Zinc acrylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Acrylic acid

EC Number:

201-177-9

EC Name:

Acrylic acid

Cas Number:

79-10-7

Molecular formula:

C3H4O2

IUPAC Name:

acrylic acid

Constituent 2

Reference substance name:

Mequinol

EC Number:

205-769-8

EC Name:

Mequinol

Cas Number:

150-76-5

Molecular formula:

C7H8O2

IUPAC Name:

4-methoxyphenol

Test material form:

liquid

Details on test material:

Composition: Acrylic acid 99.73 %, other ester adducts < 1 %, Methoxyphenol (MEHQ) ≤ 220 ppm

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Lot No. A829F1C020
- Expiration date of the lot/batch: Jan 12, 2016
- Purity: 99.73 %
- Physical description: colourless clear, pungent liquid

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test substance was administered as a 20 %, 5 % or 2.5 % w/w mixture in distilled water.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories, Inc. on February 11, March 4, and April 22, 2015
- Age at study initiation: young adult, 9 - 11 weeks
- Weight at study initiation: 157 - 199 grams at experimental start
- Fasting period before study: overnight
- Housing: singly
- Diet (e.g. ad libitum): ad libitum (except during fasting), Harlan Teklad Global 16 % Protein Rodent Diet
- Water (e.g. ad libitum): ad libitum, filtered tap water
- Acclimation period: 9 - 19 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23 °C
- Humidity (%): 40 - 57 %
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The test substance was administered as a 20 %, 5 % or 2.5 % w/w mixture in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg administered at a 20 % w/w mixture in distilled water

Doses:

2000 mg/kg as 20 % solution in distilled water
2000 mg/kg as 5 % solution in distilled water
300 mg/kg as 5 % solution in distilled water
1000 mg/kg as 2.5 % solution in distilled water

No. of animals per sex per dose:

300 and 1000 mg/kg: 6
2000 mg/kg: 3 animals for 20 % solution and 3 animals for 5 % solution

Control animals:

no

Details on study design:

- Duration of observation period following administration: short-term outcome: 48 h, long-term outcome: 14 days
- Frequency of observations and weighing: Individual body weights were recorded prior to the test substance administration (initial) and again on Days 7 and 14 (terminal) following dosing or after death. The animals were observed for mortality, signs of gross toxicity, and behavioural changes 30 min post-dosing and at least once daily thereafter for 14 days after dosing or until death occured.
- Necropsy of survivors performed: yes
- Other examinations performed: Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Statistics:

Statistical analysis was limited to the calculation of the mean density value for dosing.

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 1 000 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Mortality was observed in all animals tested with 2000 mg/kg (as 20 % and as 5 % solution) in distilled water.
One animal died after dosing of 1000 mg/kg as 2.5 % solution in distilled water.

Clinical signs:

other: All animals of the highest dose group showed hypoactivity with irregular respiration and hunched posture. All animals of the test group with 1000 mg/kg showed hypoactivity with irregular respiration and reduced fecal volume. One animal additionally showed

Any other information on results incl. tables

Table 1: Individual Body Weights, Doses and Mortalities

Animal No.	Sex	Dose Level [mg/kg]	Body weight [g]			Dose [mL]	Mortality
			Initial	Day 7	Day 14		Day	Weight [g]
3101	M	2000	164	-	-	1.6^1	1	163
3102	M		160	-	-	1.6^1	1	157
3103	M		157	-	-	1.6^1	1	154
3104	M		170	-	-	6.8^2	0	169
3105	M		176	-	-	7.1^2	0	174
3106	M		179	-	-	7.2^2	1	168
3107	M	300	199	230	258	1.2^3	S	-
3108	M		197	224	243	1.2^3	S	-
3109	M		194	226	243	1.2^3	S	-
3110	M		197	223	246	1.2^3	S	-
3111	M		192	190	200	1.2^3	S	-
3112	M		195	229	256	1.2^2	S	-
3113	M	1000	193	217	247	7.7^4	S	-
3114	M		191	145	-	7.6^4	12	138
3115	M		191	219	243	7.6^4	S	-
3116	M		188	217	236	7.5^4	S	-
3117	M		183	193	215	7.3^4	S	-
3118	M		192	218	234	7.7^4	S	-

S: Survived to study termination (euthanized via CO₂inhalation after wighing on Day 14)

¹: The test substance was administered as a 20 % w/w mixture in distilled water. Density 1.010 g/mL

²: The test substance was administered as a 5 % w/w mixture in distilled water. Density 0.998 g/mL. Due to the high volume of the dose solution to be administered (40.08 mL/kg), each animal’s dose was divided into two approximately equal portions and administered two hours apart.

³: The test substance was administered as a 5 % w/w mixture in distilled water. Density 0.998 g/mL.

⁴: The test substance was administered as a 2.5 % w/w mixture in distilled water. Density 1.003 g/mL. Due to the high volume of the dose solution to be administered (39.88 mL/kg), each animal’s dose was divided into two approximately equal portions and administered two hours apart.

Table 2: Individual Cage Side Observations

Animal Number	Dose Level [mg/kg]	Findings	Day of Occurence
3107 - 3112	300	Active and healthy	0 – 14
3113	1000	Active and healthy Hypoactivity Irregular respiration Reduced fecal volume	0 (0.5-2.5 hrs), 4 - 14 0 (3 hrs) - 2 0 (3 hrs) - 3 1 - 3
3114		Active and healthy Hypoactivity Irregular respiration Reduced fecal volume Hunched posture Unthrifty appearance Euthanized for humane reasons	0 (0.5-2.5 hrs), 4 - 6 0 (3 hrs) – 3, 7 0 (3 hrs) – 3, 7 - 12 1 – 3 7 8 – 12 12
3115		Active and healthy Hypoactivity, irregular respiration Reduced fecal volume	0 (0.5-2.5 hrs), 4 - 14 0 (3 hrs), - 3 1
3116		Active and healthy Hypoactivity, irregular respiration Reduced fecal volume	0 (0.5 hrs), 2 - 14 0 (2.5 hrs), - 1 1
3117		Active and healthy Hypoactivity, irregular respiration Reduced fecal volume	0 (0.5 hrs), 3 - 14 0 (2.5 hrs), - 1 1 - 2
3118		Active and healthy Hypoactivity, irregular respiration Reduced fecal volume	0 (0.5-2.5 hrs), 2 - 14 0 (3 hrs), - 1 1
3101 – 3103	2000	Hypoactivity, irregular respiration Hunched posture Dead	0 (0.5-5.5 hrs) 0 (3 – 5.5 hrs) 1
3104, 3105		Active and healthy Hypoactivity, irregular respiration Hunched posture Dead	0 (0.5 hrs) 0 (1.5 – 3 hrs) 0 (2.5 – 3 hrs) 0 (5 hrs)
3106		Active and healthy Hypoactivity, irregular respiration Hunched posture Dead	0 (0.5 hrs) 0 (1.5 – 5 hrs) 0 (2.5 – 5 hrs) 1

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Acute Oral LD50 is between 1000 and 2000 mg/kg b.w.

Conclusions:

An acute oral toxicity test (Acute Toxic Class Method) was conducted with rats to determine the potential for the test substance to produce toxicity from a single dose via the oral route. Under the conditions of this study, the acute oral LD50 of the test substance is between 1000 and 2000 mg/kg of body weight in male rats (equivalent to 2880 - 5760 mg zinc diacrylate/kg).

Executive summary:

A Limit Test was conducted using a starting dose level of 2000 mg/kg administered at a 20 % w/w mixture in distilled water to three healthy male rats by oral gavage. Due to mortality in these animals, three additional males were dosed at the same dose level administered at a 5 % w/w mixture in distilled water. Since all of these animals died, six additional animals in two consecutive groups of three rats each were dosed at the next lowest dose level of 300 mg/kg at a 5 % w/w mixture in distilled water. At the request of the Sponsor, a dose level of 1000 mg/kg administered at 2.5 % w/w mixture in distilled water to three healthy male rats by oral gavage. Due to mortality in one animal, three additional males were dosed at the same dose level administered at a 2.5 % w/w mixture in distilled water. Since the animals survived, no additional testing was required. All animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 days after dosing or until death occured. Body weights were recorded prior to administration (initial) and again on Days 7 and 14 (terminal) following dosing or after death. Necropsies were performed on all animals.