Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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:
reference to other study
Qualifier:
according to
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 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:
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.
Body weight:
Slight weight loss
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).

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:
reference to other study
Qualifier:
according to
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 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:
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"
Body weight:
Slight weight loss
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).

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:
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 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:
No data
Body weight:
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).

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:
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 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).

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:
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 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:
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 hunched posture and unthrifty appearance and was euthanized for humane reasons on day 12 after dosing.
All animals of the lowest dose group were active and healthy during the whole observation period.
Body weight:
One animal of the test group with 1000 mg/kg showed weight gain after 7 days post dosing.

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

-

-

1.61

1

163

3102

M

160

-

-

1.61

1

157

3103

M

157

-

-

1.61

1

154

3104

M

170

-

-

6.82

0

169

3105

M

176

-

-

7.12

0

174

3106

M

179

-

-

7.22

1

168

3107

M

300

199

230

258

1.23

S

-

3108

M

197

224

243

1.23

S

-

3109

M

194

226

243

1.23

S

-

3110

M

197

223

246

1.23

S

-

3111

M

192

190

200

1.23

S

-

3112

M

195

229

256

1.22

S

-

3113

M

1000

193

217

247

7.74

S

-

3114

M

191

145

-

7.64

12

138

3115

M

191

219

243

7.64

S

-

3116

M

188

217

236

7.54

S

-

3117

M

183

193

215

7.34

S

-

3118

M

192

218

234

7.74

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

Referenceopen allclose all

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:
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:
no effects
Body weight:
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).

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:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
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 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 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 observation period.
Body weight:
Increased as expected for all animals over the course of the study.
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)

Dose1

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.