Registration Dossier

Administrative data

Description of key information

Not irritating to skin or eye. 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

Adequate information exists to characterise the skin and eye irritation potential of Rosin Esters.

Skin Irritation

The potential for Resin acids and Rosin acids, hydrogenated, Me esters to cause skin corrosion/irritation is well understood. Two human studies and five animal studies were available for review. Results from six of these seven tests showed that the test substance was not irritating to skin, with one study (a rabbit skin test) indicating the occurrence of reversible odema at 24 hr post-treatment. These findings are briefly discussed below.

In one human study (Biosearch Inc, 1987a), conducted by generally accepted international methods for the testing of skin irritation potential in human volunteers, 0.2 mL of Resin acids and rosin acids, hydrogenated, Me esters was applied for 24 hr to the upper arms of each of one hundred and two female subjects and covered with a gauze pad secured with cloth tape (semi-occlusive conditions). There were no signs of irritation in any of the test subjects following 24-hour application. In a second human study, a repeat insult patch test (Consumer Product Testing Co., 1998a), 209 male and female subjects received 0.2 grams of the same test material applied under occlusive patch 3 times/week for a total of 9 applications. Each patch was left in place for 24 hours. There were no signs of irritation in any test subject at any time during the study.

Skin irritation studies on Resin acids and rosin acids, hydrogenated, ME esters conducted in rabbits using a method that was identical or equivalent to OECD Guideline 404 (Biosearch Inc., 1986a; EVic-CEBA, 1989d; NOTOX, 1986a, 1986b, 1986c) found generally mild, occassionally moderate, dermal responses when 0.5 mL of the undiluted test material was applied to the skin under an occlusive or semi-occlusive wrap for four hours. Erythema scores were in a range 0.5 to 2.0 during the period 24 to 72 -hours following patch removal. Edema scores over the same time period were generally negligible (score = 1 or less up to 72 -hours) although a mean score of 3 was recorded in a single study (EVic-CEBA, 1989d) at the 24 -hour time point. Following a weight of evidence assessment (which includes results from two studies performed using large groups of human volunteers), it is concluded that Resin acids and rosin acids, hydrogenated, Me esters is not irritating to skin.

In a Human Repeat Insult Patch Test, no evidence of irritation was apparent in 202 male and female test subjects exposed on the upper back three times per week for a total of ten applications to 0.2 g of the test material (Foral 85 ester; Resin acids and rosin acids, esters with glycerol) under occluded patch for 24-hours (Consumer Product Testing Co., 1997b). There were no signs of test material-related irritation in any subject at any time during the study under conditions of exposure that were significantly more stringent than the 4-hour exposures used in current animal skin irritation testing protocols.

In a dermal irritation study conducted on Bevitack 1000 (Resin acids and rosin acids, esters with glycerol), no erythema or edema was present on shaved dorsal skin from three New Zealand White rabbits exposed to 0.5 g of undiluted test substance for four hours under occlusion (Research & Consulting Company AG, 1985b). It was concluded that Bevitack 1000 is not a skin irritant.

In a rabbit skin irritation study conducted according to OECD Guideline 404, 3 rabbits were each exposed to 0.5 g of the test material Hydrogral G5 (Resin acids and rosin acids, hydrogenated esters with glycerol) under occluded contact for four hours (EViC-CEBA, 1989c). Any responses present at the treatment site were recorded 1, 24, 48, and 72 hours following termination of exposure. Slight dry skin was noted in one animal at the 24 hour timepoint, but no signs of erythema or edema were present at any time. The test sample was not a skin irritant under the conditions of the test.

In a dermal irritation study using Dertoline G2L (Resin acids and rosin acids, esters with glycerol), 0.5 g of undiluted test substance was applied to the intact and abraded shaved dorsal skin of three New Zealand White rabbits under semiocclusive contact 4 hours (Biogir SA, 1990d). The animals were then observed for 3 days for signs of primary irritation (erythema and edema). During the observation period, the test substance caused slight (2/3) to well defined (1/3) erythema on abraded skin. Erythema on intact skin was rated as slight. Edema was limited to a single animal with abraded skin at the 24 hour observation. Dryness of the skin was noted in all animals with abraded skin and 1 animal with intact skin starting 3 days after test substance administration. Under the study conditions, Dertoline G2L is, at most, minimally irritating to the skin of New Zealand White Rabbits.

In another dermal irritation study with Dertoline SG2 (Resin acids and rosin, esters with glycerol) (Biogir SA, 1990f) which followed the same protocol as above, only slight reversible erythema was apparent up to 72 hours in one animal with dryness of the skin present at 72 hours in two animals. These findings confirmed that Dertoline SG2 is, at most, minimally irritating to skin.

In a dermal irritation study with Tergum 390 (Resin acids and rosin acids, esters with glycerol), 0.5 g of test substance (moistened with water) was applied to clipped intact dorsal skin of New Zealand White male rabbits for four hours under semiocclusive contact (Center for Applied Research and Development, S. A. L., 1995a). The animals were then observed for a total of 3 days for signs of primary irritation. No erythema or edema was apparent at any timepoint indicating that the sample was not irritating to skin.

The skin irritation potential of UNITAC RLM (Resin acids and rosin acids, esters with pentaerythritol) was investigated in three male New Zealand white rabbits exposed dermally to two applications of 0.5 gram for 4 hours under semi-occluded contact with intact skin (Safepharm Laboratories Limited, 1998a). Dermal responses were observed for 72 hours. Very slight erythema was noted at the application site of two animals one hour after termination of exposure, which in one animal persisted to the 24-hour observation time before fully resolving by 48 hours. No edema was observed in any animal during the study. The test substance produced individual Primary Irritation Scores of 0.0, 0.0, and 0.3 for the three animals tested and a Primary Irritation Index of 0.1 (negligible irritation). It was concluded that the test substance is not a dermal irritant.

In a dermal irritation study conducted using Bevitack 115/15 (Resin acids and rosin acids, esters with pentaerythritol), 0.5 g of moistened test substance was applied for 4 hours under occlusion to the clipped intact dorum of three New Zealand White rabbits (1 male and 2 females) (Research & Consulting Company AG, 1985a). The animals were then observed for a total of 3 days for signs of primary irritation (erythema and edema). No dermal responses were present, indicating that the sample was not a skin irritant.

In a dermal irritation study, 0.5 g of undiluted Dertoline P2L (Resin acids and rosin acids, esters with pentaerythritol) was applied to naïve and abraded clipped skin on the backs of three New Zealand White rabbits for four hours under semiocclusive contact (Biogir SA, 1990e). The test substance caused slight (2/3 animals) to well defined (1/3 animals) erythema but no edema on three naïve skin sites; two of three naïve sites were normal at the 72-hour observation. On abraded skin, the test substance caused slight (1/3 animals) to well defined (2/3 animals) erythema accompanied by slight edema on one animal only. The effects were readily reversible. Slight dryness of the skin was also noted in all animals starting 72 hours after test substance administration. Under the study conditions, the test substance was, at most, minimally irritating to the skin of New Zealand White Rabbits.

In a dermal irritation study performed using Bevilite 62-107 (Resin acids and rosin acids, esters with pentaerythritol), 0.5 g of undiluted sample was applied to clipped dorsal skin of six New Zealand White male rabbits for four hours under semiocclusion (Centre International de Toxicologie, 1990a). The animals were observed at 1, 24, 48, and 72 hours after removal of the dressings for signs of primary irritation (erythema and edema). No dermal responses were present.

In a study that investigated the skin irritation potential of Tergum 100 (Resin acids and rosin acids, esters with pentaerythritol), 0.5 g of undiluted sample (moistened with water) was applied under semiocclusive contact for four hours to clipped skin on the back of three New Zealand White male rabbits (Centro De Investigacion Y Desarrollo Aplicado, 1995b). Mild erythema was noted 30 minutes after test substance removal in one of three animals, but this had fully reversed by the next observation period (24 hours). Edema was not observed in any animal during the 3 day observation period. Based on the results of this study, Tergum 100 is not a skin irritant.

In a study that investigated the skin irritation potential of Bevilite 62-85 (Resin acids and Rosin acids, esters with trimethylolpropane), a single dose of 500 mg of the test material (ground down to a fine dust) was applied under semi occlusive contact for four hours to clipped skin on the back of six New Zealand White female rabbits (Centre International de Toxicologie, 1990). The mean of the erythema and oedema scores was 0.0 for all observation time points. In conclusion, no cutaneous reactions were observed in all the animals.

 

In a supporting study, the test material, Sylvalite RE 80HP (Resin acids and Rosin acids, esters with trimethylolpropane) was extracted in 0.9% sodium chloride USP solution, alcohol in saline, polyethylene glycol, and cotton seed oil, NF (NAMSA, 2005). There extracts were evaluated for intracutaneous toxicity in accordance with the guidelines of the current USP. A 0.2 mL dose of the test material extract was injected by the intracutaneous route into five separate sites on the right side of the back of two New Zealand White male rabbits per extract. Under the conditions of this study, there was no evidence of significant irritation or toxicity from the extract injected into the rabbits.

Eye Irritation

The potential for Resin acids and rosin acids, hydrogenated, Me esters to cause eye irritation was investigated according to OECD Guideline 405 using a group of three rabbits (NOTOX, 1986d) No irrititation of the cornea or iris were noted during the observation period. Grade 1 conjunctival erythema was noted for all treated eyes but effects were fully reversible by Day 7. Chemosis was noted at the 1-hour observation only, with all eyes normal by the 24-hour observation time. Based on the results of this study, Resin acids and rosin acids, hydrogenated, Me esters is not corrosive and is, at most, slightly irritating to the rabbit eye.

In a primary eye irritation study conducted using Zonester 85 (Resin acids and rosin acids, esters with glycerol), slight signs of irritation were seen for the cornea, iris, and conjunctiva (Carnegie-Mellon Institute of Research, 1977a). All signs of irritation of the cornea and iris were fully reversible by the 48-hour observation. Conjunctival irritation was fully reversible for four of six rabbits by the 72-hour observation; two rabbits exhibited slight irritation to the conjunctiva during the entire observation period. Zonester 85 was, at most, a slight ocular irritant in this study.

In a primary eye irritation study with Zonester 85 Resin Ester (A) (Resin acids and rosin acids, esters with glycerol), 100 mg of test substance was instilled into the conjunctival sac of each of 6 New Zealand albino rabbits (Huntingdon Research Center, 1978a). Animals were then observed for 72 hours with any ocular reactions present graded according to the Draize scale of weighted scores. There were no adverse effects on the cornea or iris. Signs of irritation were limited to mild irritation (grade of 2-4 out of 20) of the conjunctiva in 4 of six rabbits at the 24-hour observation period. Two of six rabbits were completely normal throughout the study. One rabbit exhibited mild irritation (grade 2 out of 20) to the conjunctiva during the entire observation period. The test substance was, at most, no more than slightly irritating to the eye.

The eye irritation potential of Resin acids and rosin acids, esters with pentaerythritol was investigated in a key study in which 100 mg of undiluted PC 12-99 was instilled into the conjunctival sac of one eye of each of 9 New Zealand White rabbits (Pharmakon Research International, Inc., 1982c). Six eyes were unwashed while the remainder were immediately irrigated with water for one minute following installation. The method was equivalent or similar to OECD Guideline 405, with ocular reactions recorded at 24, 48, and 72 hours, and 4 and 7 days post-treatment using the Draize scale of weighted scores. For the six unwashed eyes, no signs of corneal opacity, iris irritation, discharge or chemosis were noted during the observation period. Slight conjunctival erythema (Grade 1) was noted for two treated eyes at the 24- and 48-hour examinations. This had reversed in one animal by the 72-hour observation and in the other by Day 4. Based on the results of this study, the test substance was, at most, slightly irritating to the rabbit eye.

Respiratory Tract Irritation

No studies in which animals were exposed to members of this category were identified. However based on a lack of significant irritation in skin irritation studies conducted in humans and rabbits and eye irritation studies in rabbits, Rosin esters are not expected to be irritating to the respiratory tract. It is also noted that the vapour pressure of these substacnes is low indicating that exposure via this route is unlikely.


Justification for selection of skin irritation / corrosion endpoint:
Information is available on the skin irritation potential of Resin acids and rosin acids, hydrogenated, Me esters, Resin acids and rosin acids, esters with glycerol, Resin acids and rosin acids, hydrogenated esters with glycerol, Resin acids and rosin acids, esters with pentaerythritol; and Resin acids and Rosin acids, esters with trimethylolpropane. The results demonstrate that Rosin esters are not irritating to the skin.

Justification for selection of eye irritation endpoint:
Information is available on the eye irritation potential of Resin acids and rosin acids, hydrogenated, Me esters, Resin acids and rosin acids, esters with glycerol and Resin acids and rosin acids, esters with pentaerythritol. The results demonstrate that Rosin esters are not irritating to the eye.

Justification for classification or non-classification

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).