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Toxicological information

Acute Toxicity: oral

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 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:
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.

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

-

-

1.61

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

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.
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.