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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:
07 July 1982 to 04 August 1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid that tends to crystallise
Details on test material:
- Appearance: clear liquid, tends to crystallise

Test animals

Species:
rat
Strain:
other: Tif:RAIF(SPF), F3-crosses of RII 1/Tif x RII2/Tif
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 180 - 196 g
- Housing: Groups of 5, in cages with standardised soft wood bedding
- Diet (e.g. ad libitum): Rat food, ad libitum
- Water (e.g. ad libitum): ad libitum
- Fasting period before study: Animals were fasted overnight before dosing.

ENVIRONMENTAL CONDITIONS
- Kept under conventional laboratory conditions.
- Air conditioned.
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 15 %
- Air changes (per hr): Approximately 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Distilled water containing 0.5 % carboxymethylcellulose and 0.1 % polysorbate 80
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bodyweight
Doses:
1000, 2500 and 5000 mg/kg
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
no
Details on study design:
OBSERVATIONS
- Period: 14 days or until all symptoms have disappeared.
- Mortality: daily am and pm on working days.
- Clinical Signs: daily.
- Bodyweight: on days 1, 7, 14 and at death.
- Necropsies: spontaneously dying animals were subjected to gross necropsy as soon as possible and survivors at the termination of the study.
Statistics:
- Bodyweights: Group means and standard deviations were calculated.
- The LD50 including the 95 % confidence limit was calculated by the logit method (Berkson, 1944).

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 793 mg/kg bw
Based on:
test mat.
95% CL:
2 648 - 6 646
Sex:
male
Dose descriptor:
LD50
Effect level:
3 821 mg/kg bw
Based on:
test mat.
95% CL:
2 178 - 25 811
Sex:
female
Dose descriptor:
LD50
Effect level:
3 821 mg/kg bw
Based on:
test mat.
95% CL:
2 178 - 25 811
Mortality:
4 males and 4 females died at the 5000 mg/kg dose level. All deaths occurred within 5 days post exposure. See Table 1 for details.
Clinical signs:
The following clinical signs were observed: sedation, dyspnoea, exophthalmus, ruffled fur and curved body position.
Surviving animals recovered within 14 days. See Table 2 for details.
Body weight:
At the higher doses, bodyweight development was highly erratic during the first week following treatment, but normalised thereafter. See Table 3 for details.
Gross pathology:
No treatment-related gross organ changes were observed.

Any other information on results incl. tables

Table 1 Mortality Data

Dose (mg/kg)

Totals

Time of Death

In the Group

Deaths

Hours After Treatment

Days After Treatment

Number

%

1

3

5

24

2

3

4

5

Males

 

1000

5

0

 

 

 

 

 

 

 

 

 

2500

5

0

 

 

 

 

 

 

 

 

 

5000

5

4

80

 

 

 

 

 

1

1

2

Females

 

1000

5

0

 

 

 

 

 

 

 

 

 

2500

5

0

 

 

 

 

 

 

 

 

 

5000

5

4

80

 

 

 

1

 

2

1

 

Table 2 Clinical Signs

Observations

Hours After Treatment

Days After Treatment

1

3

5

24

2

3

4

5

6

7

8

9

10

11

12

13

1000 mg/kg

 

Sedation

 

 

X

X

 

 

 

 

 

 

 

 

 

 

 

 

Dyspnoea

XX

XX

XX

XX

X

X

X

X

X

X

X

X

X

X

X

 

Exophthalmus

 

 

 

X

X

X

X

X

X

X

X

 

 

 

 

 

Ruffled fur

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

X

X

X

X

X

Curved body

X

X

X

X

X

X

X

X

X

X

 

 

 

 

 

 

2500 mg/kg

 

Sedation

 

X

X

X

 

 

 

 

 

 

 

 

 

 

 

 

Dyspnoea

XX

XX

XX

XX

X

X

X

X

X

X

X

X

X

X

X

 

Exophthalmus

 

 

 

X

X

X

X

X

X

X

X

X

 

 

 

 

Ruffled fur

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

X

X

X

X

X

Curved body

X

X

X

X

X

X

X

X

X

X

 

 

 

 

 

 

5000 mg/kg

 

Sedation

X

XX

XX

XX

XX

XX

XX

X

X

 

 

 

 

 

 

 

Dyspnoea

XX

XX

XX

XX

XX

XX

XX

X

X

X

X

X

X

X

X

 

Exophthalmus

 

 

 

 

 

 

 

X

X

X

X

X

X

X

 

 

Ruffled fur

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

X

Curved body

X

X

X

X

X

X

X

X

X

X

X

X

X

X

 

 

 

Table 3 Bodyweights (g)

Dose (mg/kg)

Males

Females

Day 1

Day 7

Day 14

Day 1

Day 7

Day 14

1000

183 (4.1)

237 (6.3)

272 (6.0)

184 (3.0)

211 (7.1)

226 (12.6)

2500

185 (5.0)

199 (18.9)

246 (7.9)

188 (5.4)

196 (24.3)

222 (11.1)

5000

185 (6.5)

-

-

184 (4.1)

-

-

( ) = Standard deviation

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of the test material was determined to be 3793 mg/kg in the male and female rat. The test material requires no classification in accordance with EU criteria.
Executive summary:

The acute oral toxicity of the test material was evaluated in a study conducted in accordance with the standardised guideline OECD 401.

Albino rats were administered a single oral dose of the test material by gavage at dose levels of 1000, 2500 and 5000 mg/kg bodyweight. Five animals per sex were dosed at each concentration and the animals observed for 14 days.

Four male and 4 female animals died within 5 days at the 5000 mg/kg bodyweight dose level. No further mortality was seen. Clinical signs included sedation, dyspnoea, exophthalmus, ruffled fur and exhibiting a curved body position. All survivors had recovered by the end of the observation period and no gross abnormalities were observed at necropsy.

Under the conditions of this study, the LD50 was determined to be 3793 mg/kg bodyweight and the test material requires no classification in accordance with EU criteria.