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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
January-February 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given; comparable to guidelines/standards

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Principles of method if other than guideline:
At the time of performance, OECD 425 was not available.
GLP compliance:
yes
Remarks:
in house quality system
Test type:
up-and-down procedure

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test compound: Ethomeen T/12
Batch no: 73/323422
Purity: 95%
Appearance: off-white waxy solid
Date of receipt: 26 October 1983
Storage: ambient temperature

Test animals

Species:
rat
Strain:
other: HC/HFY (remote Sprague-Dawley)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hacking and Churchill Ltd., Huntingdon, UK
- Age at study initiation: ca. 4-6 weeks
- Weight at study initiation: 81-132 g
- Fasting period before study: overnight prior to dosing until ca. 4 hours after dosing
- Housing: individually in metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): mean 42
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 10 January To: 13 February 1984

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE: methyl celluose (1%)
- Concentration in vehicle: various concentrations in vehicle to obtain dose volumes of 10.0 ml/kg


MAXIMUM DOSE VOLUME APPLIED: 10.0 ml/kg bw

Doses:
800, 1000, 1260, 1600, 2000, 2500, 4000, 5000 mg/kg bw
No. of animals per sex per dose:
1 at each dose level in time (11 males and 12 females in total)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing:soon after dosing, frequently on the remainder of the day of dosing. At least twice per
day thereafter. BW were monitored on day 0 and day and at death.
- Necropsy of survivors performed: yes
Statistics:
LD50 values were estimated by probit analysis, using a slope estimated from background data. The probit model was fitted by
maximum likelihood, with a slope of 8.333 (equivalent to a standard deviation of 0.12 units for the distribution of individual (log.)
tolerance levels). Approximate confidence intervals (95% level) were derived by adding and subtracting 1.96 times the standard
error of the (log.) LD50 estimate.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 500 mg/kg bw
95% CL:
1 100 - 2 000
Sex:
female
Dose descriptor:
LD50
Effect level:
1 200 mg/kg bw
95% CL:
900 - 1 600
Mortality:
Deaths occurred amongst rats treated at 1.26 g/kg and above from within two and three days of dosing. Autopsy revealed
haemorrhage or congestion of the lungs in the majority of animals. These findings were usually accompanied by pallor of the liver,
kidneys and spleen. Congestion of the blood vessels of the stomach was observed in one female rat treated at 1.6 g/kg and
congestion of the blood vessels of the intestine in one female rat treated at 5.0 g/kg. All rats that died showed a bodyweight loss.
Clinical signs:
Signs of reaction to treatment observed shortly after dosing in all rats included pilo-erection and abnormal body carriage (hunched
posture). Abnormal gait (waddling), lethargy and pallor of the extremities were observed in the majority of rats in all treatment
groups. Incidences of ptosis, diarrhoea and increased salivation were seen at dose levels of 1.0 g/kg and above. These signs
were accompanied by a decreased respiratory rate in rats dosed at 1.26 g/kg and above. One female rat treated at 2.0 g/kg had an abnormal gait (walking on toes). In the surviving animals, recovery as judged by external appearance and behaviour, was
apparently complete by Day 5 to 8. Pilo-erection was still observed in one male rat dosed at 1.26 g/kg and one female rat dosed at
1.0 g/kg on Day 8. This finding was not considered to be of toxicological importance and the observation period was not
extended.
Body weight:
No abnormalities in BW gain in surviving rats.
Gross pathology:
Necropsy findings in survivors were normal.
Other findings:
No data.

Any other information on results incl. tables

Mortality data

Sex

Dose (mg/kg)

Mortality data on each occasion

No. of deaths

1

2

3

4

5

6

7

8

9

10

11

12

M

1000

0

0

0/2

1260

0

0

0

0/3

1600

1

1

2/2

2000

1

1/1

2500

1

1/1

4000

1

1/1

5000

1

1/1

F

800

0

0/1

1000

0

0

0

0/3

1260

1

1/1

1600

1

1

2/2

2000

1

1

2/2

2500

1

1/1

4000

1

1/1

5000

1

1/1

0 = animal survived; 1 animal died

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The LD50 values (plus 95% confidence limits) were 1500 (1100-2000) mg/kg bw for males, and 1200 (900-1600) mg/kg bw for
females. The test compound was therefore classified in Category IV according to OECD-GHS.
Executive summary:

The study was performed to assess the acute toxicity of the test material following a single oral administration to the HC/CFY (remote Sprague-Dawley) strain rat. The study was performed equivalent to OECD 425. A group of 11 fasted males and 12 fasted female was given a single, oral dose of the test material at dose levels between 800 and 5000 mg/kg bodyweight. The animals were observed for 7 days after the day of dosing and were then killed for gross pathological examination. Deaths were observed at levels 1260 mg/kg bw and higher. Clinical signs of toxicity noted were pilo-erection, hunched posture, abnormal gait, lethargy, pallor of the extremities, ptosis, diarrhoea, increased salivation, and decreased respiratory rate. Recovery was apparently complete by day 5 -8 (day 1 is day of dosing). All surviving animals showed expected gains in bodyweight over the study period. No abnormalities were noted in survivors at necropsy. Non-survivors generally showed haemorrhage or congestion of the lungs, and pallor of the liver, kidneys and spleen. The acute median lethal dose (LD50) of the test material (with 95% confidence limits) was found to be 1500 (1100 -2000) mg/kg bw in males, and 1200 (900 -1600) mg/kg bw in females. The test compound was therefore classified in Category IV according to OECD-GHS.