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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Experimental test result performed using standard test guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
To assess the toxicity potential of test chemical after single oral administration in rats and an observation period of 14 days.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
Identification : STYRENATED PHENOL
Appearance : Clear yellowish viscous liquid
Batch number : Lot 2/04
CAS No. : 61788-44-1
AI Content : Monostyryl Phenol – 11.20%
Distyryl Phenol– 44.65%
Tristyryl Phenol– 43.59%
Manufactured date : May, 2013
Expiry Date : September, 2014
Storage conditions : Room temperature (20 - 30 °C)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Supplier / Source: In-house animals, bred at Animal House, sa-FORD. CPCSEA Registration No. 1256/bc/09/CPCSEA.
Health Status :Healthy young adult animals were used for the study. Females were nulliparous and non pregnant.
Body weight of animals :Minimum: 132 g Maximum: 158 g (Individual body weights were within ± 6% prior to treatment after overnight fasting)
Age: 8- 10 weeks at the time of dosing.
Acclimatisation:Animal nos. 1-3 were acclimatized for 5 days and 4-6 for 10 days, prior to administration of the test item.
Identification :The animals were marked temporarily on tail, permanently on toe pad micro tattooing and cage cards. Individual cage cards were labelled with study no., study type, test system, group, dose, sex, animal number experimental start and completion date.

Husbandry Conditions
Diet :All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum. Batch No.: 400004.
Bedding :All cages were provided with corn cobs (Sparconn Life Sciences Bangalore) SPAR – 25 /2014.
Water : Aqua guard filtered tap water was provided ad libitum via drinking bottles.
Husbandry :The animals were housed individually in polycarbonate cages.
Room Sanitation:The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
Cages and water bottle :All the cages and water bottles were changed at least twice every week.

Experimental Room Condition
Temperature :Minimum: 19.80 °C Maximum: 23.20 °C
Relative humidity :Minimum: 48.70% Maximum: 69.20%
Light-dark-rhythm : 12:12
Air Changes : More than 12 changes per hour

Administration / exposure

Route of administration:
oral: feed
Vehicle:
corn oil
Details on oral exposure:
The maximum dose volume administered was 10 ml/kg body weight.
Six female Wistar rats fasted for 16-18 hrs; were selected for acute oral toxicity study. The feed was withheld prior to dosing and 4 hours post dosing but drinking water was provided ad libitum. The time interval between dosing was determined by the onset, duration and severity of toxic signs. Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and one mortality was observed on day 1 post dosing. Hence, further dosing was stopped. The duration of dosing was between 11:09 to 11:29 a.m.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Six femal rates
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: After test item administration, individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all animals were observed once a day during the 14 day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed:
Clinical Observation
After test item administration, individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all animals were observed once a day during the 14 day observation period.
Mortality
All animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period.
Body weight
All rats were weighed on days 0 (prior to dosing), 7 and 14.
Pathology
At the end of 14 day observation period, all rats were euthanised by overdose of CO2 for external and internal observations.
Statistics:
Not specified

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality observed
Mortality:
No mortality was observed in the animals treated with 2000 mg/kg dose throught out the 14 days observation period, except animal no. 5 was found dead on day 1 post dosing (refer table 4).
Clinical signs:
At 2000 mg/kg, animal no. 1 was observed with normal signs at 30 minutes and 1 hour, mild lethargy at 2, 3 and 4 hours, mild diarrhea at 2, 3, 4 hours and on day 1 and normal thereafter till the end. Animal no. 2 was observed with normal signs at 30 minutes and 1 hour, mild lethargy and diarrhea at 2, 3 and 4 hours and normal from day 1 till the end. Animal no. 3 was observed with normal signs at 30 minutes and 1 hour, mild lethargy at 2, 3 and 4 hours, mild diarrhea at 3, 4 hours and on day 1 and normal from day 2 till the end. Animal no. 4 was observed with normal signs at 30 minutes and 1 hour, mild lethargy at 2, 3, 4 hours, on day 1 and 2, mild diarrhea at 2, 3 and 4 hours and normal from day 3 till the end. Animal no. 5 was observed with normal signs at 30 minutes and 1 hour, mild lethargy at 2, 3, 4 hours and on day 1, mild diarrhea, abdominal breathing and found dead on day 1. Animal no. 6 was observed with normal signs at 30 minutes and 1 hour, mild lethargy at 2, 3, 4 hours, on day 1 and 2, mild diarrhea at 3 and 4 hours and normal from day 3 till the end (refer table 3).
Body weight:
Mean Body weight of all surviving animals treated with 2000 mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0 (refer table 1 and 2).
Gross pathology:
Found dead animal no. 5 was observed with soiled anal region with feces during external examination, whereas mild red discoloration of lungs and moderately enlarged adrenals during internal examination. No external and internal gross pathological changes were seen in the other animals treated with 2000 mg/kg body weight during terminal sacrifice (refer table 5).

Any other information on results incl. tables

Table 1: Individual Animal Body Weight (g) and Body Weight Changes(%)

 

Sex:Female

Animal No.

Group/ Dose (mg/kg)

Body Weight (gram)

Body Weight Change (%)

Day 0

Day 7

Day 14

Found Dead

Day

0-7

Day

0-14

1

G1/ 2000

138

165

180

-

19.57

30.43

2

144

183

189

-

27.08

31.25

3

132

157

156

-

18.94

18.18

4

158

174

186

-

10.13

17.72

5

137

-

-

122

-

-

6

139

162

175

-

16.55

25.90

Key:- = Not applicable

Table 2: Summary of Animal Body Weight (g) and Body Weight Changes (%)

 

Sex:Female

Group/ Dose (mg/kg)

Rats Body Weight (g)

Body Weight Changes (%)

Day 0

Day 7

Day 14

0-7

0-14

G1/ 2000

Mean

141.33

168.20

177.20

18.45

24.70

SD

9.03

10.33

13.03

6.10

6.49

n

6

5

5

5

5

Keys:SD = Standard Deviation, n = Number of Animals

Table 3: Individual Animal Clinical Signs and Symptoms

 

Sex:Female

Animal No.

Group/ Dose (mg/kg)

Hours (Day 0)

1/2

1

2

3

4

1

G1/ 2000

1

1

49+

99+

49+

99+

49+

99+

2

1

1

49+

99+

49+

99+

49+

99+

3

1

1

99+

49+

99+

49+

99+

4

1

1

49+

99+

49+

99+

49+

99+

5

1

1

99+

99+

99+

6

1

1

99+

49+

99+

49+

99+

 

Animal No.

Group/ Dose (mg/kg)

Days post dosing

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1

G1/ 2000

49+

1

1

1

1

1

1

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

1

1

1

1

1

1

1

3

49+

1

1

1

1

1

1

1

1

1

1

1

1

1

4

99+

99+

1

1

1

1

1

1

1

1

1

1

1

1

5

49+

99+

4+

2

-

-

-

-

-

-

-

-

-

-

-

-

-

6

99+

99+

1

1

1

1

1

1

1

1

1

1

1

1

Keys:  - = Not applicable, 1 = Normal, 2 = Found dead, 4 = Abdominal breathing, 49 = Diarrhoea,                    99 = Lethargy,+= Mild.

Table 4: Individual Animal Mortality Record

 

Sex:Female

Animal No.

Group/ Dose (mg/kg)

Day of Observation (Day 0 to 14)

Morning Observations

Evening Observations

1

G1/ 2000

No mortality and morbidity

No mortality and morbidity

2

No mortality and morbidity

No mortality and morbidity

3

No mortality and morbidity

No mortality and morbidity

4

No mortality and morbidity

No mortality and morbidity

5

No mortality and morbidity till day 1 Found dead on day 1

No mortality and morbidity on day 0

 

6

No mortality and morbidity

No mortality and morbidity

Table 5: Gross Necropsy Observation

Sex:Female                                                                                                                                        

Animal No.

Group/ Dose (mg/kg)

Mode of Death

Gross Observation

External

Internal

1

G1/ 2000

Terminal sacrifice

No abnormality detected

No abnormality detected

2

Terminal sacrifice

No abnormality detected

No abnormality detected

3

Terminal sacrifice

No abnormality detected

No abnormality detected

4

Terminal sacrifice

No abnormality detected

No abnormality detected

5

Found

dead

No abnormality detected

Lungs: Red discoloration (mild)

Adrenal glands: Enlarged (moderate)

6

Terminal sacrifice

No abnormality detected

No abnormality detected

 



Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
Acute Oral Toxicity of test chemical was studied in Rats, This study was performed as per OECD No. 423.
Under the condition of the study,Acute oral LD50 of test chemical was determined to be >2000 mg/kg body weight
Executive summary:

Acute Oral Toxicity of test chemical was studied in Rats, This study was performed as per OECD No. 423.

Six female Wistar rats were selected for acute oral toxicity study. The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs.

Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and one mortality was observed on day 1 post dosing. Hence, further dosing was stopped.

Body weights of surviving animals were recorded on day 0 (prior to dosing) 7 and 14. The animal was weighed immediately after found dead. Mean Body weight of all surviving animals treated with 2000 mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0

Under the conditions of this; the LD50 value of test chemical in female rats was >2000 mg/kg body weight.