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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:
May 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Feb 1987
Deviations:
no
GLP compliance:
yes
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No.of test material: SN 9707
- Expiration date of the batch: not available
- Purity: > 95%
- Appearance: Pale yellow liquid

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark
- Stability, homogeneity and purity were the responsibility of the Sponsor.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Hsd/Ola:Sprague-Dawley (CD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Ltd., Bicester, Oxon, England
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: Approximately four to seven weeks
- Weight at study initiation: 106 g - 132 g
- Fasting period before study: Overnight prior to and approximately four hours after dosing
- Housing: In groups of five
- Diet: Standard laboratory rodent diet (Biosure LAD 1), ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: Seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21
- Humidity (%): 45 (mean)
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12, 0700 - 1900 light phase

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.06 ml/kg using a syringe and plastic catheter
Doses:
2,000 mg/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Check for any mortalities at least twice daily. Bodyweight of each rat was recorded on Days 1 (prior to dosing), 8, and 15. Individual weekly bodyweight chnages were calculated.
- Necropsy of survivors performed: yes, animals were killed on Day 15 by cervical dislocation
- Other examinations performed: clinical signs (animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 - a period of five hours. On subsequent days, animals were observed once in the morning and again at the end of the experimental day), macroscopic pathology (opening the abdominal and thoracic cavities, appearance of all tissues was recorded)

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed
Clinical signs:
Pilo-erection and increased salivation were observed in all rats within five minutes of dosing. Pilo-erection persisted and was accompanied at later intervals on Day 1 by abdominal body carriage (hunched posture) and abdominal gait (waddling). Recovery of all rats, as judged by external appearance and behaviour, was complete by Day 2.
Body weight:
All rats achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No macroscopic abnormalities were observed.

Any other information on results incl. tables

Table 1: Clinical signs of reaction to treatment observed in rats

Signs

No. of rats in group of 5 showing signs

Dose (g/kg)

2.0

males

females

Pilo-erection

5

5

Abnormal body carriage (hunched posture)

5

5

Abnormal gait (waddling)

5

5

Increased salivation

5

5

Table 2: Individual bodyweights

Sex

Dose (g/kg)

Animal number and ear mark

Bodyweight (g) at

 

 

 

Day 1

Day 8

Day 15

Males

2.0

1 RP

2 LP

3 RPLP

4 RIRO

5 LILO

131

130

125

132

128

184

192

197

200

183

234

236

249

254

226

Females

2.0

6 RP

7 LP

8 RPLP

9 RIRO

10 LILO

125

116

114

106

122

163

158

156

141

167

174

196

176

158

192

Table 3: Individual bodyweight changes

Sex

Dose (g/kg)

Animal number and ear mark

Bodyweight (g) at

 

 

 

Week 1

Week 2

Males

2.0

1 RP

2 LP

3 RPLP

4 RIRO

5 LILO

53

62

72

68

55

50

44

52

54

43

Females

2.0

6 RP

7 LP

8 RPLP

9 RIRO

10 LILO

38

42

42

35

45

11

38

20

17

25

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute lethal oral dose to rats of the test substance was found to be greater than 2,000 mg/kg bodyweight. The test substance does not require labelling with the risk phrases R22 "Harmful if swallowed", in accordance with Council Directive 79/831/EEC Annex VI, Part II(D) as described in Commission Directive 91/325/EEC.
Executive summary:

A study was performed to assess the acute oral toxicity of the test substance to the rat. The method followed was that described in:

- EEC Methods for the determination of toxicity, Directive 84/449/EEC (OJ No. L251, 19.9.84), Part B, Method B. 1. Acute toxicity (oral).

- EPA Health Effects Testing Guidelines, Subpart B - General Toxicity Testing 5798.1 175 Acute oral toxicity, September 27, 1985 (described in Federal Register Vol. 50, No. 188) and subsequent revisions. Subpart B provides detailed information relating to data requirements of 40 CFR Part 158 and supports the Toxic Substances Control Act (TSCA).

- OECD Guideline for Testing of Chemicals No. 401 "Acute Oral Toxicity". Adopted: 24 February 1987.

A group of ten fasted rats (five males and five females) was given a single dose by gavage of the test substance, as supplied, at a dose level of 2.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period. There were no deaths. Clinical signs of reaction to treatment included pilo-erection, abnormal body carriage, abnormal gait and increased salivation; recovery was complete by Day 2. All rats achieved satisfactory bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic examination on Day 15. No target organs were identified on the basis of clinical observations and macroscopic observations at necroscopy .

The acute lethal oral dose to rats was found to be greater than 2.0 g/kg bodyweight.