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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
January 22, 1981 - February 4, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
May not be GLP compliant. Control animals were not mentioned. As no signs of toxicity were seen in 10 rats it is safe to assume that Soybean oil, epoxidised is not toxic therefore this deviation should not be an issue. Read across to a study result from an investigation using a similar material is justified for members of the Epoxidised Oils and Derivatives group. Four epoxidised oils and esters (linseed, soybean,9-octadecanoate propylene glycol ester and 2-ethylhexyl tallate ester ETP). The C14-C22, 2-ethylhexylesters are listed as similar products on the market to ETP based on fatty acids from other naturally occurring fatty acids This group of epoxies are identified as sharing common structural and functional similarities, recognised in an OECD SIDS review as a single category, and therefore justifying read-across between data for different members of the group. Consequently data sharing between ESBO epoxidised soybean oil, ELO epoxidised Linseed oil and ETP epoxidised 2ethylhexyl tallate and fatty acids, C14-C22, 2-ethylhexylesters, epoxidised is commonly utilised in the preparation of this dossier. Read-across bridges are used for members of the EOD group where appropriate, is justified based on similar toxicity profiles and structural and functional similarities.
Justification for type of information:
Read across to a study result from an investigation using a similar material is justified for members of the Epoxidised Oils and Derivatives group. Four epoxidised oils and esters (linseed, soybean,9-octadecanoate propylene glycol ester and 2-ethylhexyl tallate ester ETP). The C14-C22, 2-ethylhexylesters are listed as similar products on the market to ETP based on fatty acids from other naturally occurring fatty acids. This group of epoxies are identified as sharing common structural and functional similarities, recognised in an OECD SIDS review as a single category, and therefore justifying read-across between data for different members of the group. Consequently data sharing between ESBO epoxidised soybean oil, ELO epoxidised Linseed oil and ETP epoxidised 2ethylhexyl tallate and fatty acids, C14-C22, 2-ethylhexylesters, epoxidised is commonly utilised in the preparation of this dossier. Read-across bridges are used for members of the EOD group where appropriate, is justified based on similar toxicity profiles and structural and functional similarities.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Conduct of the study predates formal adoption of the test guideline but in principle the OECD 401 limit method was followed. No vehicle control animals were included. The vehicle, designated PAG in the report, was not tested separately.
Principles of method if other than guideline:
Although pre-dating the formal guideline, the study was conducted in general concordance with a limit test as described in OECD method 401. The vehicle selected was described as PAG with no elucidation. It is assumed that it was polyethylene glycol (PEG), which was comonly used for acute gavage administration and this would explain the absence of a separate vehicle control group.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): TK 11278
- Physical state: Liquid
- Lot/batch No.: prod. Oct. 80


Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.
The test material was dispersed in PAG - probably polyethylene glycol (PEG) and administered in a dose volume of 20 mL/kg bw.

Test animals

Species:
rat
Strain:
other: Tif: RAIf (SPF) Strain
Sex:
male/female
Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Healthy random bred rats of the Tif:RAIf (SPF) strain , which were raised on the Ciba-Geigy Ltd, Basle, laboratory premises
- Age at study initiation: 7 to 8 weeks old
- Weight at study initiation: male mean = 185g; female mean = 174g
- Fasting period before study: rats were fasted overnight prior to treatment
- Housing: in groups of 5 in Macrolan cages
- Diet (e.g. ad libitum): NAFAG, Gossau SG
- Water (e.g. ad libitum): potable water source not specified in report
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 14/10

IN-LIFE DATES: From: 22 January 1981 To: 4 February 1981

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: PAG. Assumed to be PEG = polyethylene glycol
Details on oral exposure:
The report indicates PAG was used as a vehicle (it is assumed this is a typographical error and that PEG, polyethylene glycol was actually used).
The test material was dispensed at 20 ml/kg bw.

Animals were fasted overnight and treated by single oral intubation.
Doses:
5000 mg/kg
No. of animals per sex per dose:
5 animals per group
Control animals:
not specified
Details on study design:
Bodyweights were recorded immediately prior to dosing and after 7 and 14 days. Physical condition and mortality were monitored throughout the observation period.
Statistics:
LD50 including 95 % confidence limits are calculated by the logit model.

Results and discussion

Preliminary study:
Not relevant
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
None of the rats died
Clinical signs:
See Table 2 below
Evidence of slight dyspnoea, slightly ruffled fur, slight diarrhoea and a slightly curved body position were noted primarily on Day 1 (1-24 h after administration). Some cases of ruffled fur and curved body position persisted on days 2 to 4.
Body weight:
See Table 1 below
Gross pathology:
No gross organ changes were observed
Other findings:
No further information supplied

Any other information on results incl. tables

Table 1: Bodyweight change

 

Dose – 5000 mg/kg

Mean (g)

Standard Deviation (g)

Day 1 (Male)

185

1.8

Day 1 (Female)

174

1.2

Day 7 (Male)

236

5.1

Day 7 (Female)

186

1.8

Day 14 (Male)

289

5.7

Day 14 (Female)

215

2.9

  

Table 2: Clinical Signs

Dose – 5000 mg/kg

Signs and Symptoms

Hours

Days

1

2

3

5

24

2

3

4

5

6

7

8

9

10

11

12

13

14

Sedation

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Dyspnoea

+

+

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Dacryorrhoea

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chromodacryorrhoea

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Rinorrhoea

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Epistaxis

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Exophthalmos

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Salivation

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Ruffled fur

+

+

+

+

+

+

+

+

 

 

 

 

 

 

 

 

 

 

Pallor

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Cyanosis

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Diarrhoea

 

+

+

+

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Body Position (ventral)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Body Position (lateral)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Body Position (curved)

+

+

+

+

+

+

 

 

 

 

 

 

 

 

 

 

 

 

Ataxia

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Trismus

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Tremor

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Tonic clonic muscle spasms

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Convulsions

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 + = slight

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 of TK 11'278 in rats of both sexes observed over a period of 14 days is greater than 5000 mg/kg. The test material is therefore practically non toxic to the rat by this route of administration. According to Regulation (EC) No. 1272/2008, no classification is warranted.
Executive summary:

The acute oral LD50 of TK 11'278 in rats of both sexes observed over a period of 14 days is greater than 5000 mg/kg. The test material is therefore practically non toxic to the rat by this route of administration. According to Regulation (EC) No. 1272/2008, no classification is warranted.