Fatty acids, C16 and C18-20 (even numbered, unsaturated), 2-ethylhexyl esters

Carcinogenicity

Description of key information

A non-standard study of dermal carcinogenesis with the read-across substance ESBO in the mouse is available.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: dermal

Type of information:

experimental study

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.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Not stated - the assay contains range-finding data for comparative assessment of 60 epoxy compounds. Data or results or tabulated comparisons are presented for a range of acute toxicity investigations (see IUCLID Data Points 7.2.1; 7.3.1; 7.4.1 and 7.3.2) and a carcinogenicity assessment based on lifetime skin painting studies with mice and an evaluation of mouse sebaceous gland suppression. The carcinogenicity investigations were designed as range-finding studies intended to rank differences between biepoxides and mono-epoxides and to highlight areas for further investigation, rather than following specific test guidelines.

GLP compliance:

no

Species:

mouse

Strain:

C3H

Sex:

not specified

Details on test animals or test system and environmental conditions:

Age: 90 day old mice. Groups of 30-40 mice used per test substance.

Route of administration:

other: skin painting

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: hair wasremovedfrom the dorsum of 90-day old mice
- % coverage: not stated
- Type of wrap if used: No indication of occlusion
- Time intervals for shavings or clipplings: The report does not specifiy times for re-clipping

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not stated

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): One brushful of test material was painted onto the dorsal midline. Three applications per week for 24 months
- Concentration (if solution): undiluted liquid epoxidised soybean oil
- Constant volume or concentration used: yes - stated to be one "brushful" per application. No more specific assessment of the dose is provided

VEHICLE
- Justification for use and choice of vehicle (if other than water): applied undiluted

Mice were painted with a small amount of undiluted ESBO, applied to the clipped dorsal midline on alternate days of the working week (3 times /week) for up to 24 months. No more details of the methods are provided in the publication.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

Maximum number of months painted : 24 months

Frequency of treatment:

three times per week (Monday/Wednesday/Friday)

Post exposure period:

The mice were observed until death.

Remarks:

Doses / Concentrations:

Basis:
nominal conc.
Undiluted material applied but no quantifiaction of the dose

No. of animals per sex per dose:

30 - 40 mice were used

Control animals:

not specified

Details on study design:

Carcinogenicity
The hair was removed with electric clippers, as necessary, from the backs of 90-day old mice. The mice received three applications per week - one brushful of chemcial being applied to the midline of the back on Monday, Wednesday and Friday. Observations were made for papillomas and carcinomas during each painting period. Groups of 30 - 40 mice were used for each test material in the comparison

The liquid material was applied undiluted. The mice were observed until death.

Whenever a tumour was seen on the skin, a plot of its position was made and a record of its progress was kept. The median tumour or cancer latent periods were calculated by the method suggested by Horton. These latent periods are the lengths of time necessary to reach a 50 % tumour or cancer index. The indices are calculated as - 100 times the number of mice with skin tumours or with cancers, divided by the "effective group" where "effective group" is the number of mice given adequate exposure. This is the original number of mice employed less the number that have died without tumours. It is, therefore, a variable number that decreases by one with each non-tumour death. It is, however, arbitrarily held constant after the time of the appearance of a tumour in the median tumour-bearing mouse.

The sebaceuos gland test involved the daily application of one brushstroke of the chemical, on five days the first week and four the second week. The day after the last painting all surviving mice were killed, the skin was subsequently fixed, embedded, sectioned and stained. The number of sebaceous glands per square centimeter of skin was counted and related to the number present in the skin of control mice.

An advantage of this nine-application test other than its reduction in elapsed time, is the indication of the toxicity of the chemical before it is used for life-time painting. ESBO was not included in the sebaceous glans assay but other mono-epoxidised materials were included in the investigation.

Positive control:

No data

Observations and examinations performed and frequency:

An assessment of mortality was presented. The number of mice alive after 12 months = 36; the number alive after 17 months = 26 and the number alive after 24 months of treatment = 0.

Sacrifice and pathology:

No data

Other examinations:

The number of mice alive after 24 months was assessed (= 0 for ESBO).
The total numbers of mice with tumours (=0 for ESBO) or cancers (= 0 for ESBO) after 24 months was assessed.
Tumour Index = 0
Cancer Index =0
Median latent period in months for tumours/cancer could not be determined in the absence of any carcinogenicity.

Statistics:

No data

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

The number of mice alive after 12 months = 36; the number alive after 17 months = 26 and the number alive after 24 months of treatment = 0.
The number of mice alive after 24 months was assessed (= 0 for ESBO).
The total numbers of mice with tumours (=0 for ESBO) or cancers (= 0 for ESBO) after 24 months was assessed.
Tumour Index = 0
Cancer Index =0
Median latent period in months for tumours/cancer could not be determined in the absence of any carcinogenicity.

Relevance of carcinogenic effects / potential:

ESBO gave no indications of carcinogenicity potential.

Dose descriptor:

other: Tumour Index/Cancer Index/Median Latent Period

Based on:

test mat.

Remarks:

Repeated dermal application of an undefined quantity of ESBO for 24 months did not result in evidence of tumorigenicity or carcinogenicity

Sex:

not specified

Remarks on result:

other:

Remarks:

Effect type: other: No effects observed in this study (migrated information)

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. ESBO was not included in the SGT battery of tests.

Conclusions:

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

Classification for carcinogenicity is not justified based on the data available.

Additional information

The hair was removed with electric clippers from the backs of 90-day old mice. The mice received three applications per week - one brushful of chemical being applied to the midline of the back on Monday, Wednesday and Friday. Observations were made for papillomas and carcinomas during each painting period. Groups of 30 - 40 mice were used for each test material in the comparison. The liquid material was applied undiluted. The mice were observed until death. Whenever a tumour was seen on the skin, a plot of its position was made and a record of its progress was kept. The median tumour or cancer latent periods were calculated by the method suggested by Horton. These latent periods are the lengths of time necessary to reach a 50 % tumour or cancer index. The indices are calculated as - 100 times the number of mice with skin tumours or with cancers, divided by the "effective group" where "effective group" is the number of mice given adequate exposure. This is the original number of mice employed less the number that have died without tumours. It is, therefore, a variable number that decreases by one with each non-tumour death. It is, however, arbitrarily held constant after the time of the appearance of a tumour in the median tumour-bearing mouse. The sebaceuos gland test involved the daily application of one brushstroke of the chemical, on five days the first week and four the second week. The day after the last painting all surviving mice were killed, the skin was subsequently fixed, embedded, sectioned and stained. The number of sebaceous glands per square centimeter of skin was counted and related to the number present in the skin of control mice. An advantage of this nine-application test other than its reduction in elapsed time, is the indication of the toxicity of the chemical before it is used for life-time painting. ESBO was not included in the sebaceous gland assay but other mono-epoxidised materials were included in the investigation. There was no indication of carcinogenicity in this study.