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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:
21 July 1998 to 9 September 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD guideline 401 with minor deviation: the certificate of analysis and purity of the test substance are missing.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No certificate of analysis
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
yes
Remarks:
No certificate of analysis
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Substance type: liquid
- Physical state: liquid
- Analytical purity: not advised
- Lot/batch No.: EE 665
- Expiration date of the lot/batch: not advised but assumed to be 6 months from the date of receipt
- Storage condition of test material: 4°C in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan U.K. Ltd, Oxon, England
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 85-97 g
- Fasting period before study: overnight before dosing and for 4 h after dosing
- Housing: in groups of 5 of the same sex
- Diet (e.g. ad libitum): Special Diet Services RMI(E) SQC expanded pellet, ad libitum (except in fasting period)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 18
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21 July 1998 To: 9 September 1998

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.944 mL/kg bw
Doses:
Preliminary experiment: 3200 mg/kg bw
Main study: 2000 mg/kg bw
No. of animals per sex per dose:
Preliminary experiment: 1
Main study: 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: at least twice daily for mortality. At frequent intervals for clinical signs the day after dosing and twice daily thereafter. Body weights were recorded on day 1 (just before dosing) and day 8 for the preliminary experiment and on days 1, 8 and 15 for the main study.
- Necropsy of survivors performed: yes (macroscopic examination)
Statistics:
None

Results and discussion

Preliminary study:
At 3200 mg/kg bw, the male rat died within 22 h of dosing. Clinical signs prior to death and in the surviving rat comprised piloerection, hunched posture, walking on toes, abnormal faeces, ungroomed appearance and increased salivation in both animals. In addition, pallid extremities was seen in the female only. There were no other signs of reaction and, with the exception of piloerection, recovery was complete in the female by Day 7. Macroscopic examination of the decedent animal revealed congestive changes (characterised by dark appearance/prominent blood vessels) in the subcutaneous tissue, brain, heart, liver and spleen. Congestion with gaseous distension and fluid contents were also noted in the stomach and along the alimentary tract. No macroscopic abnormalities were noted in the remaining animal at the terminal necropsy on Day 8.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths
Clinical signs:
Piloerection was observed in all rats within five minutes of dosing. This sign persisted and was accompanied in rats later on Day 1 and/or at later intervals during the study by: hunched posture, waddling/unsteady gait, lethargy, pallid extremities, walking on toes, abnormal faeces, thin appearance, ungroomed appearance and dark colouring to eyes, seen in all rats. These signs were accompanied in one or more rats by increased salivation and swollen abdomen.
Recovery of surviving rats, as judged by external appearance and behaviour, was complete in all females by Day 7 and in all males by Day 10.
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No macroscopic abnormalities were observed for animals killed at study termination on Day 15.
Other findings:
No data

Any other information on results incl. tables

Table 1: Individual and group mean bodyweights (g)

Phase of

study

Dose

(mg/kg)

Animal No.

& Sex

Bodyweight (g) at

Day 1

Day 8

Day 15

Death

Preliminary

3200

1 M

96

-

-

84

2 F

99

140

-

-

Main

2000

11M

87

142

197

-

12 M

93

143

188

-

13 M

91

146

193

-

14 M

92

146

194

-

15 M

85

135

175

-

Mean

90

142

189

-

16 F

97

146

171

-

17 F

96

147

176

-

18 F

90

126

151

-

19 F

89

132

158

-

20 F

93

136

165

-

Mean

93

137

164

-

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 for TMPeoTA is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI to the Directive 67/548/CEE and the CLP Regulation (1272/2008).
Executive summary:

In an acute oral toxicity study performed in accordance with GLP and OECD guideline 401, groups of Sprague Dawley rats (5/sex) were given a single oral dose of TMPeoTA undiluted at 2000 mg/kg bw. In a preliminary study, one male and one female received a single oral dose of TMPeoTA undiluted at 3200 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 8 days in the preliminary experiment and for 15 days in the main study. They were all macroscopically necropsied after death or sacrifice.

In the preliminary experiment, the male rat died within 22 h of dosing. Macroscopic examination of the decedent animal revealed congestive changes (characterised by dark appearance/prominent blood vessels) in the subcutaneous tissue, brain, heart, liver and spleen. Congestion with gaseous distension and fluid contents were also noted in the stomach and along the alimentary tract. Such effects were not observed in the female rat. In the main study, piloerection was observed in all rats within five minutes of dosing. This sign persisted and was accompanied in rats later on Day 1 and/or at later intervals during the study by: hunched posture, waddling/unsteady gait, lethargy, pallid extremities, walking on toes, abnormal faeces, thin appearance, ungroomed appearance and dark colouring to eyes, seen in all rats. These signs were accompanied in one or more rats by increased salivation and swollen abdomen. Recovery of surviving rats, as judged by external appearance and behaviour, was complete in all females by Day 7 and in all males by Day 10.

The oral LD50 for TMPeoTA is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (1272/2008).