Overbased reaction products of distilled tall oil and magnesium hydroxide’

Endpoint summary

Description of key information

Fatty acids C18-(unsaturated) lithium salts, rosin, hydrogenated rosin and rosin oligomers are not irritating to skin or eye. Divalent cationic salts of Rosin and Hydrogenated rosin are insoluble and their irritation potential is therefore comparable to that of the parent substance. Low vapour pressure precludes inhalation exposure.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

Results from investigations of the skin irritation potential of salts of unsaturated fatty acids, resin and rosin acids and supporting data on rosin and rosin reaction products are summarised briefly below:

The potential for fatty acids C18-(unsaturated) lithium salts to cause skin irritation and skin corrosion has been evaluated in vitro.

An in vitro test (Warren, N., 2010) was conducted to evaluate the skin irritation potential of the test material using the EPISKIN^TMreconstituted human epidermis model after a treatment period of 15 minutes, followed by a post-exposure incubation period of 42 hours.At the end of the post-exposure incubation period each tissue was taken for MTT-loading. The maintenance medium from beneath each tissue was transferred to pre-labelled micro tubes and stored in a freezer for possible inflammatory mediator determination. After MTT loading a total biopsy of each epidermis was made and placed into micro tubes containing acidified isopropanol for extraction of formazan crystals out of the MTT-loaded tissues. At the end of the formazan extraction period each tube was mixed thoroughly and duplicate 200 µl samples were transferred to the appropriate wells of a pre-labelled 96-well plate. The optical density was measured at 540 nm.

The relative mean viability of the test material treated tissues was 93.1% after a 15-minute exposure. The test material was considered to be non-irritating to the human epidermis.

A further in vitro test (Warren, N., 2010) was conducted to evaluate the skin corrosion potential of the test material using the EPISKIN^TM in vitro Reconstituted Human Epidermis (RHE) Model after treatment periods of 3, 60 and 240 minutes. At the end of each exposure period the test material was rinsed from each tissue before each tissue was taken for MTT loading. After MTT loading a total biopsy of each epidermis was made and placed into micro tubes containing acidified isopropanol for extraction of formazan crystals out of the MTT-loaded tissues. After formazan extraction, each tube was mixed thoroughly and duplicate 200 µl samples were transferred to the appropriate wells of a pre-labelled 96 -well plate. The optical density was measured at 540 nm. The relative mean viability of the test material treated tissues were 127.3%; 128.9%, and 89.8%, post 240-, 60-, and 3-minutes, respectively.

Based on the results above, the test material was not considered to be corrosive to the skin.

The potential for Resin acids and rosin acids, hydrogenated, potassium salts to cause skin irritation has been evaluated in vitro and in vivo. In the in vitro investigation, the test substance was found to be inactive in a CORROSITEX™ assay (Eastman Kodak Company, 2004c); a satisfactory response was obtained with the positive and negative control substances included in the test. In the in vivo test (OECD Guideline 404), three New Zealand white rabbits were exposed to 0.5 g of Resin acids and rosin acids, hydrogenated, potassium salts for 4 hours under occluded contact with intact skin and observed for 72 hours. There were no signs of test material-related erythema or edema at any time during the study. In addition, no signs of erythema or edema were observed in a dermal toxicity study in which male and female rats were exposed to the test material under occluded contact for 24 hours (see Eastman Kodak Company, 2004b). Based on these data, Resin acids and rosin acids, hydrogenated, potassium salts is not considered to be a primary skin irritant.

In a primary dermal irritation study, six young adult New Zealand white rabbits (2 males, 4 females) were exposed to 0.5 g of UNITAC 70 (Rosin, reaction products with formaldehyde) applied for 24 hours under occluded contact to intact and abraded skin (Food & Drug Research Laboratories, Inc., 1985c). Animals were then observed for a period of 72 hours post-treatment. Irritation was scored by the method of Draize. The conditions of exposure in this study were significantly more stringent, i. e., 24 hours on intact and abraded skin, than the current OECD 404 guidelines that specify a 4-hour exposure period on intact skin with a semi-occlusive dressing. Examinations at 24.5 and 72 hours post-treatment with the undiluted test substance moistened with saline indicated no signs of erythema or edema on the abraded or intact skin of the six rabbits. Based on these findings, UNITAC 70 was not considered to be a skin irritant to rabbits.

In a primary dermal irritation study on Hydrogenated rosin (Rosin, hydrogenated), 12 New Zealand white rabbits were dermally exposed to 0.5 gram of test substance for twenty-four (24) hours on intact (n=6) or abraded (n=6) skin (CIVO-Institutes TNO, 1982). Animals were observed for seventy-two (72) hours. On intact skin, the test substance caused the appearance of very slight to well-defined erythema and only very slight edema following twenty-four (24) hour contact. By forty-eight (48) hours after patch removal, edema was absent and erythema was barely perceptible. Hydrogenated rosin was therefore not irritating to rabbit skin.

In a primary dermal irritation study, three male New Zealand white rabbits were exposed dermally, on intact skin, to 0.5 gram of Gum Rosin (Rosin) for 4 hours under semi-occlusive contact (Phycher Bio Development, 2010c). Animals were then observed for a period of 72 hours post-treatment. Irritation was scored by the method described in OECD Guideline 404. Except for slight erythema noted at the application site of a single rabbit one hour after termination of exposure, no signs of skin irritation (erythema and/or edema) were evident during 24-, 48-, or 72-hour examinations. Based on mean values of 0 for both erythema and edema at the 24-, 48-, and 72-hour observations, Gum Rosin was not irritating to rabbit skin.

The irritation potential of Rosin, hydrogenated (also known as Hydrogral, Foral AX, and Staybelite Resin-E) was evaluated based on the results of a Human Repeat Insult Patch Test (Industrial Bio-Test Laboratories Inc., 1977). Although the available study predates current regulatory guidelines, the procedure followed standard scientific methodology in effect at the time the study was conducted. There was no evidence of an irritation response in 53 male and female test subjects exposed three times per week for three weeks to 0.2 mL of a 50% solution of the test material in corn oil applied under occlusive patch for twenty-three (23) hours. The conditions of exposure were significantly more stringent than the 4-hour exposures used in current animal testing. There were no signs of test material-related irritation in any subject at any time during the study.

Eye irritation

In a primary ocular irritation study (Bradshaw, J., 2010),a single application of the test material (fatty acids C8-(unsaturated) lithium salts to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. One treated eye appeared normal at the 72 Hour observation and the other treated eye appeared normal at the 14 Day observation. The test material produced a maximum group mean score of 12.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

An in-vitro study (Warren, N., 2010) was conducted to evaluate theeye irritation potential of the test material (fatty acids, C18-(unsaturated) lithium salts) using the SkinEthic Reconstituted Human Corneal model (HCE, SkinEthic Laboratories, France). Triplicate SkinEthic tissues were treated with 30 mg of the test material for 10 minutes. Triplicate tissues treated with 30 µl of Solution A served as the negative control and triplicate tissues treated with 30 µl of 1% w/v Sodium Dodecyl Sulphate served as the positive control. At the end of the exposure period each SkinEthic tissue was rinsed. The rinsed tissues (two per group) were taken for MTT loading. The remaining tissues were retained for possible histopathology. Following MTT loading the reduced MTT was extracted from the tissues.

After extraction the absorbency of triplicate aliquots of the extracted MTT solution for each SkinEthic tissue was measured. The optical density was measured at 540 nm (OD₅₄₀).  The relative mean viability of the test material treated tissues after a 10 minute exposure was determined to be 86.5%. Therefore, the test material was considered to be non-irritating to the eye.

The potential for Resin acids and rosin acids, hydrogenated, potassium salts to cause eye irritation was evaluated after instillation into the eyes of six New Zealand White rabbits (Eastman Kodak Company, 2005b). Immediately after instillation, the eyes of three rabbits were irrigated with distilled water while the eyes of the other three rabbits were not.  There were no adverse effects on the cornea or iris in either washed or unwashed eyes. Signs of irritation in unwashed eyes included slight to severe chemosis and slight to moderate redness of the conjunctivae. Mean scores for conjunctival redness in unwashed eyes were 2 at the 24-, 48-, and 72-hour examinations. Mean scores for chemosis in unwashed eyes were 2, 2.33 and 1.33 at the 24-, 48- and 72-hour examinations, respectively. In washed eyes, signs of irritation were limited to slight redness of the conjunctivae. Irritation was fully reversible in the unwashed eyes by 7 days and in washed eyes by 72 hours. Based on the results of this study, Resin acids and rosin acids, hydrogenated, potassium salts is irritating to rabbit eye.

In a primary eye irritation study, 0.1 gram of UNITAC 70 (Rosin, reaction products with formaldehyde) was instilled into the conjunctival sacs of each of six young adult New Zealand white rabbits (4 males, 2 females) (Food & Drug Research Laboratories, Inc., 1985d). The remaining eye of each rabbit served as a control. All eyes were examined with fluorescein and the grade of ocular reaction for each animal was recorded at 24, 48, and 72 hours post-treatment using the Draize scale for scoring ocular lesions. Slight signs of irritation were seen for the cornea, iris, and conjunctiva. The mean eye irritation score was determined for each observation period. The overall mean eye irritation scores (± S. D.) out of a possible 110 points were 5.7 (± 6.1) at 24 hours, 3.0 (± 5.5) at 48 hours, and 0 at 72 hours. All treated eyes were normal by the 72-hour examinations. Based on the scoring and classification systems in the study report, the test substance was not considered to be irritating to rabbit eyes.

In a primary eye irritation study, three female New Zealand white rabbits were administered 0.1 gram of Gum Rosin (Rosin) into the conjunctival sac of one eye, the remaining eye of each rabbit serving as a control (Phycher Bio Development, 2010d). All treated eyes were examined and the grade of ocular reaction for each animal was recorded at 1, 24, 48, and 72 hours post-treatment. Due to the persistence of ocular reactions, the treated eye of a single rabbit was also examined and graded on Days 4, 7, and 8. Grades of ocular reactions were determined using the Scale of Weighted Scores for Grading the Severity of Ocular Lesions (standard Draize criteria). No signs of corneal irritation were evident for any treated eye at any time during the study. Iris irritation was limited to a single eye (Grade 1) at the 1-hour examination. Ocular conjunctivae reactions included redness (Grades 2-3) reversible between Days 3 and 8 and chemosis (Grades 2-3) reversible between Days 2 and 4. Discharge (Grade 2-3) was also reported early in the study. One eye was normal by Day 8 and the remaining two eyes appeared normal by 72 hours. The mean eye irritation scores (from the 24-, 48-, and 72-hour examinations) were calculated for each animal for classification purposes. Mean scores (chemosis, redness, iris lesions, and corneal opacity) reported were 1.3, 1.3, 0, and 0 for Animal #1; 0.3, 0.7, 0, 0 for Animal #2; and 0.3, 0.7, 0, 0 for Animal #3, respectively. Based on the evaluation criteria used in this study, Gum Rosin was considered to be minimally irritating to rabbit eye.

Respiratory tract irritation

No studies were identified, however a low vapour pressure indicates that exposure via this route is unlikely.

Justification for selection of eye irritation endpoint:
Note: the monovalent salts are irritating to eye.

Justification for classification or non-classification

Fatty acids C18-(unsaturated) lithium salts, rosin, hydrogenated rosin and rosin oligomers: Not classified for skin or eye irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Divalent salts of Rosin and Hydrogenated rosin: Not classified for skin or eye irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).