Registration Dossier

Administrative data

Description of key information

Studies of acute oral and dermal toxicity are available, and show low toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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.
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
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
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.
Preliminary study:
Not relevant
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

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

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.

Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Study period:
1963
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Very little information provided on the materials and methods of the study. 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.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Not stated - the tabulated results indicate a determination of the median lethal dose which suggests a standard acute toxicity method e.g. OECD Method 401
GLP compliance:
no
Test type:
other: Rangefinding test determining oral LD50 in rats in terms of mL/kg and dermal toxicity in rabbits in mL/kg bw among other acute endpoints
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No further data supplied for range-finding studies
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
This report does not provide details on oral exposure.
Doses:
Dose levels are not specified for the oral range finding test
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
No details given in publication for the study design used to determine acute median lethal dose. More information supplied for other testing referenced in this paper - see cross references above. The design appears to be a reasonably conventional OECD 401 type test.
Statistics:
No data supplied
Preliminary study:
No data supplied
Sex:
not specified
Dose descriptor:
LD50
Effect level:
22.5 mL/kg bw
Based on:
test mat.
95% CL:
14 - 36
Mortality:
No data supplied. Median lethal dose determined as 22.5 ml/kg bw
Clinical signs:
No data supplied
Body weight:
No data supplied
Gross pathology:
No data supplied
Other findings:
See cross references to this summary in IUCLID Data Points 7.3.1, 7.3.2 and 7.4.1

Toxicity

A wide range of toxicity and irritation of epoxy monomers is documented in this report. No consistent correlations with structure are evident.

Range-finding results are reported for a number of acute investigations including oral, dermal and inhalation toxicity, skin and eye irritancy and skin sensitisation potential.

The median lethal oral gavage dose in rats was calculated to be 22.5 mL/kg bw.

Carcinogenicity

The test was successfully completed. The test material was not considered to be tumorigenic to the mouse skin.

Sebaceous Gland Suppression

The mean number of sebaceous glands per square centimeter of skin of epoxide-dosed mice has been graded against that of the control mice. As the material was applied undiluted, it was compared to a distilled water control group. This substance was tested by both the sebaceous gland (S.G.T.) and the lifetime tests (L.T.T.). The L.T.T. was negative, the tumour and the cancer index were both 0.0. It was given a S.G.T. grade of 0.

The authors of this report have indicated that the S.G.T., based on the data in this report, is merely a crude screen to indicate potential L.T.T. tumorigens, not a test to be used to from definite positive or negative conclusions concerning tumorigenesis.

Interpretation of results:
GHS criteria not met
Conclusions:
A range of toxicity and irritation results for various epoxy monomers is documented in this report. No consistent correlations with structure are evident.
The median lethal oral dose was calculated to be 22.5 ml/kg bw for rats
Executive summary:

Carcinogenic and acute toxicity potential of the test material was assayed.

Irritation

The irritation result given is provided for irritation on an uncovered rabbit belly and was given a score of 2.

Toxicity

A wide range of toxicity and irritation of epoxy monomers is documented in this report. No consistent correlations with structure are evident.

Carcinogenicity

The test was successfully completed. The test material was not considered to be tumorigenic to the mouse skin.

Sebaceous Gland Suppression

The mena number of sebaceous glands per square centimeter of skin of epoxide-dosed mice has been graded against that of the control mice. As the material was applied undiluted, it was compared to a distilled water control group. This substance was tested by both the sebaceous gland (S.G.T.) and the lifetime tests (L.T.T.). The L.T.T. was negative, the tumour and the cancer index were both 0.0. It was given a S.G.T. grade of 0.

The authors of this report have indicated that the S.G.T., based on the data in this report, is merely a crude screen to indicate potential L.T.T. tumorigens, not a test to be used to from definite positive or negative conclusions concerning tumorigenesis.

Sensitisation:

Sensitisation of guinea pigs was determined by a technique consisting of eight intracutaneous injections (three per week on alternate days) of 0.1 mL of the diluted epoxy materials. A three week incubation period was followed by a challenge dose, and examinations for possible sensitisation reactions were made 24 and 48 hours thereafter.

It was concluded that the test material was not sensitising.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
20 000 mg/kg bw

Additional information

Justification for classification or non-classification

Based on the available data, classification for acute toxicity under the CLP Regulation is not required.