Zinc acrylate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(No data about doses, controls, observation frequency, fasting period before study, age at study initiation, housing of animals)

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

Swiss

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Panlab (Barcelona, Spain)
- Age at study initiation: No data
- Weight at study initiation: 24-28 g
- Fasting period before study: No data
- Housing: No data
- Diet: Standard pellet diet, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 7 d

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 0.2 mL/30 g body weight

DOSAGE PREPARATION: Solutions were administered at pH between 6.0 and 7.0. Sodium bicarbonate was used to adjust the pH when necessary.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A preliminary screening with small groups of 3 animals was carried out The LD50 values were then calculated according to the Litchfield and Wilcoxon method.

Doses:

No data

No. of animals per sex per dose:

Preliminary screening: Three
Final study: Ten

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations: No data
- Necropsy of survivors performed: No
- Other examinations performed: Clinical signs and weight gain

Preliminary study:

A preliminary screening with small groups of three animals was carried out. The LD50 values were then calculated according to the Litchfield and Wilcoxon method

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 926 mg/kg bw

95% CL:

> 636 - < 1 350

Remarks on result:

other: equivalent to 211 mg Zn/kg bw or 668 mg zinc diacrylate/kg bw

Mortality:

Mortality occurred mostly during the first 48 h of the test material administration. No deaths occurred after three days.

Clinical signs:

other: Conjunctivitis, piloerection, asthenia, decreased food and water consumption and hemorrhages and hematomas in the tail were observed. See Table 1 in "Remark on results including tables and figures" field.

Gross pathology:

No data

Other findings:

No data

Table 1. Severity of physical and clinical signs in mice after zinc intoxication in a single dose

	Number of days after zinc administration
	1	2-3	4-7	8-14
Mortality rates on oral administration	90%	10%	0%	0%
Conjunctivitis	None	+	+	None
Piloerection	None	+	+	+
Hemorrhages and hematomas in the tail	None	+	+++	+++
Asthenia	++	++	+	None
Degreased food and water consumption, weight loss	None	+	+	None

Mortality rates and physical and observational examination of rats are average for all zinc compounds.

+Light; ++Moderate; +++Severe

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 of the test substance in Swiss albino mice was determined to be 926 mg/kg bw (equivalent to 211 mg Zn/kg bw or 668 mg zinc diacrylate/kg bw)

Executive summary:

A study was conducted to evaluate the acute oral toxicity of the test substance in Swiss albino mice according to the OECD Guideline 401 (Acute Oral Toxicity). Initially, a preliminary screening with small groups of three mice was carried out and the LD50 values were then calculated according to the Litchfield and Wilcoxon method. The main study was conducted with ten mice. Mortality occurred mostly during the first 48 h of the test substance administration. No deaths occurred after three days. Conjunctivitis, piloerection, asthenia, decreased food and water consumption and severe haemorrhages and 211 mg Zn/kg bw or 668 mg zinc diacrylate/kg bw) (Domingo, 1988).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(No data about doses, controls, observation frequency, fasting period before study, age at study initiation, housing of animals)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Panlab (Barcelona, Spain)
- Age at study initiation: No data
- Weight at study initiation: 230-280 g
- Fasting period before study: No data
- Housing: No data
- Diet: Standard pellet diet (Panlab, Barcelona, Spain), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 7 d

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 1 mL/300 g body weight

DOSAGE PREPARATION: Solutions were administered at pH between 6.0 and 7.0. Sodium bicarbonate was used to adjust the pH when necessary.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A preliminary screening with small groups of 3 animals was carried out The LD50 values were then calculated according to the Litchfield and Wilcoxon method.

Doses:

No data

No. of animals per sex per dose:

Preliminary screening: Three
Final study: Ten

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: No
- Other examinations performed: Clinical signs and weight gain

Preliminary study:

A preliminary screening with small groups of three animals was carried out. The LD50 values were then calculated according to the Litchfield and Wilcoxon method

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 710 mg/kg bw

95% CL:

> 1 260 - < 2 330

Remarks on result:

other: equivalent to 389 mg Zn/kg bw or 1234 mg zinc diacrylate/kg bw

Mortality:

Mortality occurred mostly during the first 48 h of the test material administration. No deaths occurred after three days.

Clinical signs:

other: Miosis, conjunctivitis and hemorrhages and hematomas in the tail were observed in the treated animals. See Table 1 in "Remark on results including tables and figures"

Gross pathology:

No data

Other findings:

No data

Table 1. Severity of physical and clinical signs in rats after zinc intoxication in a single dose

	Number of days after zinc administration
	1	2-3	4-7	8-14
Mortality rates on oral administration	90%	10%	0%	0%
Miosis	+	++	++	+
Conjunctivitis	+	++	+	None
Erythema, necrosis in nose	None	++	++	++
Exophthalmos	None	None	None	None
Degreased food and water consumption, weight loss	None	+	+	None
Hemorrhages and hematomas in the tail	None	++	++	+

Mortality rates and physical and observational examination of rats are average for all zinc compounds.

+Light; ++Moderate

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 of the test substance was determined to be 1710 mg/kg bw (equivalent to 389 mg Zn/kg bw or 1234 mg zinc diacrylate/kg bw) (Domingo, 1988).

Executive summary:

A study was conducted to evaluate the acute oral toxicity of the test substance in rats according to OECD Guideline 401 (Acute Oral Toxicity). Initially, a preliminary screening with small groups of three rats was carried out and the LD50 values were then calculated according to the Litchfield and Wilcoxon method. The main study was conducted with ten rats. Miosis, conjunctivitis, decreased food and water consumption, haemorrhages and hematomas in the tail were observed in the rats. Based on these results, the acute oral LD50 of the test substance was determined to be 1710 mg/kg bw (equivalent to 389 mg Zn/kg bw or 1234 mg zinc diacrylate/kg bw) (Domingo, 1988).

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, short report, few details but meets basic scientific principles.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

The test substance was administered orally in graduated doses to several groups of experimental animals, one dose being used per group. The doses chosen were based on the results of a range finding test. Subsequently observations of effects and deaths were made. Animals which die during the test were necropsied, and at the conclusion of the test the surviving animals were sacrificed and necropsied.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Acclimation period: 5 d

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The selections of doses was based on the dose-range-finding study

Doses:

- Dose-range finding study: 10, 100 & 1,000 mg/kg bw
- Main study: 1,000, 1,600, 2,900 & 5,000 mg/kg bw

No. of animals per sex per dose:

- Dose-range finding study: Three animals/dose
- Main study: Each dose was given to groups consisting of one, two, three and five animals.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d or until death or increase in body weight of the survived animals
- Frequency of observations and weighing: As per OECD TG 401, individual weights of animals were determined shortly before the test substance was administered, weekly thereafter and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: Body weight and histopathology

Statistics:

No data

Preliminary study:

Not applicable

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

2 280 mg/kg bw

Based on:

test mat.

Remarks on result:

other: (equivalent to 518 mg Zn/kg bw or 1645 mg zinc diacrylate/kg bw)

Mortality:

- At 1,000 mg/kg bw = 0/3 animals
- At 1,600 mg/kg bw = 1/11 animals
- At 2,900 mg/kg bw = 9/11 animals
- At 5,000 mg/kg bw = 11/11 animals
For more details see Table 1 & Table 2

Clinical signs:

other: No data

Gross pathology:

No data

Other findings:

None

Table 1: Dose-range finding study

Doses (mg/kg bw)	Mortality
10	0/3
100	0/3
1,000	0/3

Table 2: Main study: investigations of the acute oral toxicity in male rats

Doses (mg/kg bw)	Number of animals in each group
	1	2	3	5	Total
1,000	0/3	0/3	0/3	0/3	0/3
1,600	0/1	0/2	1/3	0/5	1/11
2,900	1/1	2/2	2/3	4/5	9/11
5,000	1/1	2/2	3/3	5/5	11/11
LD50	2,150	2,150	2,250	2,500	2,280

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 of the test substance was calculated to be 2280 mg/kg bw (equivalent to 518 mg Zn/kg bw or 1645 mg zinc diacrylate/kg bw)

Executive summary:

A study was conducted to evaluate the acute oral toxicity of the test substance to male rats. A dose-range finding study was conducted at 10, 100 and 1000 mg/kg bw in which no mortality was observed at any dose level. Based on the results of dose-range finding study, three to eleven male rats were exposed to single dose of the test substance at 1000, 1000, 2900 and 5000 mg/kg bw and observed for signs of toxicity for 14 d or until death or increase in body weight of the surviving animals. Based on the results, the acute oral LD50 of the test substance was calculated to be 2280 mg/kg bw (equivalent to 518 mg Zn/kg bw or 1645 mg zinc diacrylate/kg bw) (Lorke, 1983).

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: Range finding toxicity study according to test method described by Smyth HF Jr et al. (1962)

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

- Age at study initiation: 4-5 weeks
- Weight at study initiation: 90-120g

Route of administration:

oral: gavage

Doses:

The dosages were arranged in a logarithmic series differing by a factor of two. No further data

No. of animals per sex per dose:

5

Details on study design:

- Duration of observation period following administration: 14 days

- Test conditions and method according to Smyth et al. (1962):
Single oral dose toxicity was estimated by the gastric intubation of groups of five non-fasted, Carworth-Wistar male rats, or in rare instances of female rats, four to five weeks of age and 90 to 120 grams. The dosages were arranged in a logarithmic series differing by a factor of two. Whenever possible, the chemical was administered undiluted. When a lesser concentration was necessary, solution in water or corn oil or suspension in semi-solid agar were the preferred expedients. Occasionally, a 1 % solution of Tergitol penetrant 7 (essentially an aqueous solution of 25 % sodium 3,9-diethyl-6-tridecanol sulfate) has been used as a dispersing agent. Based upon mortalities during a 14-day observation period, the most probable LD50 value and its fiducial range were estimated by the method of Thompson (1947).

Statistics:

The most probable LD50 value and its fiducial range were estimated by the method of Thompson (1947).

Thompson WR (1947). Use of Moving Averages and Interpolation to Estimate Median Effective Dose. Bacteriol. Rev. 11: 115

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 357 mg/kg bw

95% CL:

ca. 200 - ca. 609

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of the test, the test substance revealed an oral LD50 of 357 mg/kg bw.

Executive summary:

A range finding toxicity study with the test substance was conducted in rats according to the test method described by Smyth HF Jr et al. (1962). Under the conditions of the test, the test substance revealed an oral LD50 of 357 mg/kg bw (equivalent to 1028 mg zinc diacrylate/kg) (Carpenter, 1974 and Smyth, 1962).

Reference 5

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

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

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.

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:

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.

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

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 071 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Used in EU risk assessment report for zinc sulphate, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

not specified

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

Details on study design:

observation period of 15 days

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: (equivalent to 45529 mg Zn/kg bw or 1443 mg zinc diacrylate/kg bw)

Mortality:

none

Clinical signs:

other: no effects

Gross pathology:

no effects

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the dermal LD50 was >2000 mg/kg bw (equivalent to 455 mg Zn/kg bw or 1443 mg zinc diacrylate/kg bw).

Executive summary:

Zinc sulphate heptahydrate was administered to the skin of five Wistar rats of each sex at 2000 mg/kg bw for 24 h. Animals were observed for 15 days. Clinical signs of toxicity consisted of erythema (grade 1 and 2, of maximum grade 4), scales and/or scabs (scale 1 and 2, of maximum scale 3) in the treated skin area between observation days 2-8. Zinc sulphate was not harmful or toxic via the dermal route. Under the study conditions, the dermal LD50 was >2000 mg/kg bw (equivalent to 455 mg Zn/kg bw or 1443 mg zinc diacrylate/kg bw) (Van Huygevoort, 1999).

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

08. Feb. - 22. Feb. 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: U.S. EPA Health Effects Test Guidelines, OCSPP 870.1200

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Robinson Services, Inc.
- Age at study initiation: 13 weeks
- Weight at study initiation: 1937 - 2221 g (males), 1814 -2176 g (females)
- Fasting period before study:
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Purina Rabbit Chow #5326
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum by an automatic water dispensing system.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22°C
- Humidity (%): 22-38 %
- Air changes (per hr): 10 - 14
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

The 2000 mg/kg of body weight of a 20% aqueous dilution of the test substance in distilled water (v/v) was applied evenly over a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface) and covered with a 4-inch x 8-inch, 6-ply gauze pad. The gauze pad and entire trunk of each animal were then wrapped with 3-inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test substance. The rabbits were then returned to their designated cages. The day of application was considered Day 0 of the study. After 24 hours of exposure to the test substance, the pads were removed and the test sites were gently cleansed of any residual test substance.

Duration of exposure:

24 hours

Doses:

2000 mg/kg of body weight of a 20 % aqueous dilution of th etest substance in distilled water

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

Individual body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination). The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours after application and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the
first several hours after application and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous
membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma. Individual body weights of the animals were recorded prior to test substance application
(initial) and again on Days 7 and 14 (termination).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: Other than the dermal irritation, discoloration, fissuring and/or mechanical damage noted at the dose site of all animals throughout the 14-day observation period, there were no other clinical findings recorded for any animal over the course of the observ

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Other findings:

none reported

Animal No.	Sex	Body weight (g)			Dose^1
		Initial	Day 7	Day 14	mL
3801	M	1955	2124	2296	19.2
3802	M	2104	2288	2404	20.7
3802	M	2221	2287	2409	21.8
3804	M	1937	2071	2142	19.0
3805	M	2008	2042	2189	19.7
3806	F	2176	2344	2513	21.4
3807	F	2007	2167	2389	19.7
3808	F	2009	2064	2218	19.7
3809	F	1814	1946	2092	17.8
3810	F	2046	2086	2286	20.1

 

¹The test substance was applied as a 20% v/v mixture in distilled water. Specific Gravity - .1.017 g/mL

 

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the single dose acute dermal LD50 of the acrylic acid was > 2000 mg/kg bw in male and female rabbits (equivalent to > 5760 mg zinc diacrylate/kg).

Executive summary:

An acute dermal toxicity test was conducted with rabbits to provide information on the potential health hazards from short-term exposure to acrylic acid at non-corrosive concentrations via the dermal route. The substance was tested as a preparation of 20% acrylic acid in water to produce toxicity from a single topical application. All animals survived exposure to 2000 mg/kg bw and gained body weight during the study. Dermal irritation, discoloration, fissuring and/or mechanical damage was noted at the dose site of all animals throughout the 14 d observation period. There were no other findings recorded for any animal over the course of the observation period, also necropsy did not show gross abnormalities. Under the conditions of this study, the single dose acute dermal LD50 of the acrylic acid was > 2000 mg/kg bw in male and female rabbits (BAMM, 2011).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 313 mg/kg bw

Additional information

Oral

Zinc sulphate studies

Study 1:

A study was conducted to evaluate the acute oral toxicity of the test substance in rats according to OECD Guideline 401 (Acute Oral Toxicity). Initially, a preliminary screening with small groups of three rats was carried out and the LD50 values were then calculated according to the Litchfield and Wilcoxon method. The main study was conducted with ten rats. Miosis, conjunctivitis, decreased food and water consumption, haemorrhages and hematomas in the tail were observed in the rats. Based on these results, the acute oral LD50 of the test substance was determined to be 1710 mg/kg bw (equivalent to 389 mg Zn/kg bw or 1234 mg zinc diacrylate/kg bw) (Domingo, 1988).

Study 2:

A study was conducted to evaluate the acute oral toxicity of the test substance in Swiss albino mice according to the OECD Guideline 401 (Acute Oral Toxicity). Initially, a preliminary screening with small groups of three mice was carried out and the LD50 values were then calculated according to the Litchfield and Wilcoxon method. The main study was conducted with ten mice. Mortality occurred mostly during the first 48 h of the test substance administration. No deaths occurred after three days. Conjunctivitis, piloerection, asthenia, decreased food and water consumption and severe haemorrhages and hematomas in the tail vein were observed in the treated mice. Based on the above results, the acute oral LD50 of the test substance in Swiss albino mice was determined to be 926 mg/kg bw (equivalent to 211 mg Zn/kg bw or 668 mg zinc diacrylate/kg bw) (Domingo, 1988).

Study 3:

A study was conducted to evaluate the acute oral toxicity of the test substance to male rats. A dose-range finding study was conducted at 10, 100 and 1000 mg/kg bw in which no mortality was observed at any dose level. Based on the results of dose-range finding study, three to eleven male rats were exposed to single dose of the test substance at 1000, 1000, 2900 and 5000 mg/kg bw and observed for signs of toxicity for 14 d or until death or increase in body weight of the surviving animals. Based on the results, the acute oral LD50 of the test substance was calculated to be 2280 mg/kg bw (equivalent to 518 mg Zn/kg bw or 1645 mg zinc diacrylate/kg bw) (Lorke, 1983).

 

Acrylic acid studies

Study 1:

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).

Study 2:

A range finding toxicity study with the test substance was conducted in rats according to the test method described by Smyth HF Jr et al. (1962). Under the conditions, the test substance revealed an oral LD50 of 357 mg/kg bw (equivalent to 1028 mg Zn diacrylate/kg) (Carpenter, 1974 and Smyth, 1962).

 

Dermal

 

Zinc sulphate studies

Zinc sulphate heptahydrate was administered to the skin of five Wistar rats of each sex at 2000 mg/kg bw for 24 h. Animals were observed for 15 days. Clinical signs of toxicity consisted of erythema (grade 1 and 2, of maximum grade 4), scales and/or scabs (scale 1 and 2, of maximum scale 3) in the treated skin area between observation days 2-8. Zinc sulphate was not harmful or toxic via the dermal route. Under the study conditions, the dermal LD50 was >2000 mg/kg bw (equivalent to 455 mg Zn/kg bw or 1443 mg zinc diacrylate/kg bw) (Van Huygevoort, 1999).

 

Acrylic acid studies

An acute dermal toxicity test was conducted with rabbits to provide information on the potential health hazards from short-term exposure to acrylic acid at non-corrosive concentrations via the dermal route. The substance was tested as a preparation of 20% acrylic acid in water to produce toxicity from a single topical application. All animals survived exposure to 2000 mg/kg bw and gained body weight during the study. Dermal irritation, discoloration, fissuring and/or mechanical damage was noted at the dose site of all animals throughout the 14 d observation period. There were no other findings recorded for any animal over the course of the observation period, also necropsy did not show gross abnormalities. Under the conditions of this study, the single dose acute dermal LD50 of the acrylic acid was > 2000 mg/kg bw in male and female rabbits (equivalent to > 5750 mg Zn diacrylate/kg)

(BAMM, 2011).

Justification for classification or non-classification

The acute oral LD50 values for the zinc and the acrylic acid components of zinc acrylate are in the range of > 300 to ≤ 2000 mg/kg bw. According to EU CLP (EC 1272/2008) criteria, the substance therefore warrants classification as Acute Tox. 4 – H302 (Harmful if swallowed). Based on dermal LD50 values > 2000 mg/kg bw, no acute dermal classification is required.