Tall oil, maleated

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Adequate information exists to characterise the skin sensitisation potential of Rosin Adducts and Rosin Adducts Salts.

The maleate salts are formed when the fatty acids or rosin acids react with maleic anhydride.

The available data includes results of tests conducted using Rosin, fumarated, Rosin, maleated, Rosin, fumarated, reaction products with formaldehyde, and

fatty acids, C14-18 and C16-18-unsatd., maleated.

In a skin sensitization study using the Local Lymph Node Assay, groups of mice were given daily applications of 0%, 0.5%, 5%, or 50%(w/v) Rosin, fumarated in acetone/olive oil 4:1 which was applied to the dorsal surface of each ear for 3 consecutive days (Safepharm Laboratories Limited, 2002). A control group received the vehicle only in the same manner. On Day 5, 3HTdR was injected into the tail vein, the auricular lymph nodes collected 5 hr later, and a single cell suspension prepared. 3HTdR incorporation by the cells was determined, and the Stimulation Index (SI) calculated for each dose of the test substance. The pooled Stimulation Index was 1.2, 7.0, and 12.8, respectively. Based on the results, Rosin, fumarated was a skin sensitizer in mice in an OECD 429 compliant study.

In a skin sensitization study using the Local Lymph Node Assay, groups of mice were given daily applications of 0%, 0.5%, 5%, or 50%(w/v) Rosin, maleated in acetone/olive oil 4:1 (Safepharm Laboratories Ltd, 2002). The pooled Stimulation Index was 1.91, 22.84 and 19.27, respectively. Based on the results, Rosin, maleated was a skin sensitizer in mice in an OECD 429 compliant study.

In a skin sensitization study using the Local Lymph Node Assay, groups of mice were given daily applications of 0%, 0.5%, 5%, or 50%(w/v) Rosin, fumarated, reaction products with formaldehyde in acetone/olive oil 4:1 which was applied to the dorsal surface of each ear for 3 consecutive days (Safepharm Laboratories Limited, 2003). A control group received the vehicle only in the same manner. On Day 5, 3HTdR was injected into the tail vein, the auricular lymph nodes collected 5 hr later, and a single cell suspension prepared. 3HTdR incorporation by the cells was determined, and the Stimulation Index (SI) calculated for each dose of the test substance. The pooled Stimulation Index was 0.9, 3.0, and 7.2, respectively. Based on the results, Rosin, fumarated, reaction products with formaldehyde was a skin sensitizer in mice in an OECD 429 compliant study.

In a key LLNA assay, healthy female mice of the CBA/J Rj strain were topically administered, for three consecutive days, the test material (fatty acids, C14-18 and C16-18-unsatd., maleated) at concentrations of 0, 5, 10, 25, and 50% (w/v) in a acetone/olive oil vehicle (4:1 v/v). A pre-screen test was also conducted at concentrations of 25% and 50% in the same vehicle. Hexyl cinnamic aldehyde (25% w/v) was utilized as the positive control. Four female mice per dose level were used for the test material while the vehicle control and positive control groups comprised 8 and 4 mice, respectively. All formulations were freshly prepared on each day of administration. Each animal was checked twice a day (pre- and post- treatment) on Days 1 to 3 and once daily on Days 4 to 6 for signs of ill health or toxicity. At the same intervals, ears were examined for signs of irritation. In addition, individual bodyweights were recorded on Days 1 (prior to treatment) and 6 (three days after the third induction administration). On Day 6, all animals were injected into the tail vein Tritiated (^3H)-methyl Thymidine (^3HTdR) diluted in sterile phosphate buffered saline at a nominal dose of 20 µCi per mouse, to measure lymphocyte proliferation by radioactive labelling. Five hours (± 30 minutes) afterwards the draining (auricular) lymph nodes were excised and pooled for each experimental group. After sample processing and precipitating macromolecules (DNA) of the lymph node cells in 5% trichloracetic acid (TCA), radioactivity measurements were performed on Day 7. Radioactivity was expressed as the number of radioactive disintegrations per minute (DPM). The ratio of the proliferation (reflected by the magnitude of measured DPM/node) in treated groups to that in the vehicle control group, termed the stimulation index (SI) or test/control ratio, was subsequently calculated for each group. Background ^3HTdR levels were also measured in two 1 mL aliquots of 5% TCA and accounted for in the study results. The test material was regarded as a sensitizer if at least one concentration of the test substance produced a stimulation index (SI) ≥ 3.

 

No mortality or signs of systemic toxicity were evident in any test group. Lymph nodes of animals in the test material and positive control groups were observed to be larger than in vehicle control animals. All control animals and animals treated with 5 or 10% w/v test material dilution were free from clinical signs or local irritation during the entire study. At 25 and 50% w/v, all main test animals showed rigid ears with test item precipitate on them from Day 2 to Day 6, erythema grade 1 (very slight in degree) and alopecia, the latter increasing in incidence of affected animals as the study progressed. The erythema were only transient having disappeared in all animals treated with 25% w/v by Day 5 and in animals treated with 50% w/v by Day 3 or 4. Rigid ears, erythema grade 1 and alopecia were also seen in the pre-screen.Bodyweight was unaffected by treatment with the test material, both in the pre-screen and in the main test.

 

A stimulation index (SI) of 10.6 was attained for the positive control, demonstrating the reliability and sensitivity of the assay. Additionally, disintegrations per lymph node value were observed to be within the historical reference range. Mortality, cutaneous reactions or signs of toxicity were not evident in the positive control group. For the vehicle control group, 179.1 DPM/node were recorded. Overall DPM/lymph node values for the experimental groups treated with 5, 10, 25 and 50% w/v test material dilutions were 2449.3, 5030.1, 11264.4 and 12869.8 DPM/node, respectively. Stimulation Index (SI) values for the experimental groups treated with 5, 10, 25 and 50% w/v test material dilutions were 13.7, 28.1, 62.9 and 71.9, respectively. Based on the SI values attained above, the test material fatty acids, C14-18 and C16-18-unsatd., maleated,is considered to be skin sensitizer in this LLNA assay in the mouse.

In a study using Rosin, maleated (CAS 8050-28-0) in olive oil, male guinea pigs (20 males per test group and 10 control males) were tested using the Guinea Pig Maximization Test (Central Toxicology Laboratory, 1997). Test animals were induced by intradermal injections with a 0.003% w/v concentration. In addition, these guinea pigs were topically induced with a 30% concentration of the test substance in olive oil. Along with the test animals, two groups of control animals (10 per group), previously not induced with the test substance, were challenged topically for 24 hours with concentrations of 10 or 30% of the test substance in olive oil. Skin examinations at 24 hours after the completion of the challenge exposure indicated that 15 of the 19 animals in the treatment group challenged with 10% and all treated animals challenged with 30% exhibited a positive response. Based on the results of this study, Rosin, maleated was considered to be a skin sensitizer to guinea pigs.

In another supporting study conducted using the Buehler method, 20 guinea pigs were induced weekly by topical administration of 80% concentration of Rosin, maleated in olive oil (Eurofins Product Safety Laboratories, 2007). In addition, 10 guinea pigs assigned to control groups received only the vehicle during the induction period. Along with the test animals, the controls (previously not induced with the test substance) were challenged topically with concentrations of 5% of the test substance in the vehicle. Skin examinations at 24 hours after the completion of the challenge exposure resulted in a positive response for 16 of the 20 animals in the treatment group. Therefore, Rosin, maleated was considered to be a skin sensitizer to guinea pigs.

Migrated from Short description of key information:
Capable of causing sensitisation by skin contact.

Justification for selection of skin sensitisation endpoint:
Based on test data available for te main constituents and/or similar materials.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Not expected to induce or elicit respiratory sensitization, with low potential for exposure due to low volatility.

Migrated from Short description of key information:
Not expected to induce or elicit respiratory sensitization, with low potential for exposure due to low volatility.

Justification for classification or non-classification

Classified for skin sensitisation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 and UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).