Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Adequate information exists to characterise the skin sensitisation potential of Rosin Esters.

Local lymph node assay

In a skin sensitization study using the Local Lymph Node Assay (SafePharm Laboratories Limited, 2002a), three groups of 4 (CBA/CaCruBR) female mice were administered daily applications of 50 µL (25 µL per ear) Glycerol Ester of Tall Oil (Resin acids and rosin acids, tall-oil, esters with glycerol, chemically equivalent to Resin acids and rosin acids, esters with glycerol) at test concentrations of 0.5, 5, and 50% (w/v) in a 4:1 acetone: olive oil vehicle for 3 consecutive days. A control group of 4 mice received the vehicle only. Five days after the first application, the animals were injected via the tail vein with 250 µL of phosphate buffered saline containing ^3H-methyl thymidine and euthanized 5 hours later. The auricular lymph nodes were collected and a single cell suspension was prepared for each dose group. The ^3HTdR incorporation by the cells was determined and a Stimulation Index of less than 3.0 recorded for all dose concentrations. Under the conditions of the study, this test substance was not a skin sensitizer in mice.

In another study using the Local Lymph Node Assay (SafePharm Laboratories Limited, 2002b), three groups of 4 female mice were administered daily applications of 25 µL of a concentration of 0.1, 1.0, or 10% (w/v) of Phase I Pentaester of Gum Resin (Resin acids and rosin acids, esters with pentaerythritol) in acetone/olive oil (4:1 v/v) to the dorsal surface of each ear for 3 consecutive days. A control group of 4 mice received the vehicle only in the same manner. On Day 5, ^3HTdR was injected into the tail veins of the animals, and five hours later, the animals were euthanatized. After termination of the in-life phase, the auricular lymph nodes were collected and a single cell suspension was prepared. The ^3HTdR incorporation by the cells was less than 3 for each of the three concentrations of the test material. Based on the results of this study, Phase I Pentaester of Gum Resin was not a skin sensitizer in mice.

Guinea pig sensitisation studies

In a skin sensitization study using the Guinea Pig Maximization Test method (NOTOX, 1986e), 20 female guinea pigs assigned to the test group were induced by intradermal injections (Day 0) with a 5.0% and 10% concentration of Resin acids and rosin acids, hydrogenated, Me esters in corn oil. In addition, these guinea pigs were topically induced (Day 7) with a 100% concentration of the test material. Along with the test animals, a group of 8 female control animals, previously not induced with the test material, were challenged with concentrations of 0, 10, 50, and 100% of the test material in corn oil. Skin examinations at 24 and 48 hours after the challenge exposure indicated no positive sensitization reactions in the test or negative control groups. Based on the results of this study, Resin acids and rosin acids, hydrogenated, Me esters was not considered to be a skin sensitizer to guinea pigs, and therefore, presents a low skin sensitization hazard upon skin contact under conditions of normal use.

In another Guinea Pig Maximization Test (NOTOX, 1986f), 19 female guinea pigs were induced by intradermal injections (Day 0) with 5.0% and 10% concentrations of Resin acids and rosin acids, hydrogenated, Me esters in corn oil. In addition, these guinea pigs were topically induced (Day 7) with a 100% concentration of the test material. Along with the test animals, a group of 10 female control animals, previously not induced with the test material, were challenged with concentrations of 0, 10, 50, and 100% of the test material in corn oil. Skin examinations at 24 and 48 hours after the challenge exposure indicated no positive sensitization reactions in the test or negative control groups. Based on the results of this study, Resin acids and rosin acids, hydrogenated, Me esters was not considered to be a skin sensitizer to guinea pigs, and therefore, presents a low skin sensitization hazard upon skin contact under conditions of normal use.

In a third skin sensitization study on Resin acids and rosin acids, hydrogenated, Me esters (Consumer Product Testing Co., 1997b), 10 guinea pigs (5/sex) assigned to the test group were induced by intradermal injections (Day 0) with a 10% test substance in corn oil and 5% test material in a FCA/water emulsion. In addition, these guinea pigs were topically induced (Day 7) with a 100% concentration of the test material. Along with the test animals, a group of 10 (5/sex) control animals, previously not induced with the test material, were challenged with concentrations of 1% of the test material in petrolatum. Skin examinations at 24 and 48 hours after the challenge exposure indicated no positive sensitization reactions in the test group of animals. Based on the results of this study, Resin acids and rosin acids, hydrogenated, Me esters was not considered to be a skin sensitizer to guinea pigs, and therefore, presents a low skin sensitization hazard upon skin contact under conditions of normal use.

In a guinea pig maximization test using Bevilite 62-L (Resin acids and rosin acids, esters with triethylene glycol), 20 female guinea pigs were intradermally injected with the following: Freund's complete adjuvant diluted with an equal volume of water for irrigation, test substance (7.5%) in Alembicol D, and test substance (7.5%) in a 50:50 mixture of Freund's complete adjuvant and Alembicol D (Huntingdon Research Centre Ltd, 1992a). Six days after the intradermal injections, the animals were exposed topically to a 10% solution of sodium lauryl sulfate to induce local inflammation. The following day 0.4 mL Bevilite 62-L (neat, as supplied) was topically applied and remained in contact with the skin for 48 hours. Two weeks after the induction period, the animals were challenged for 24 hours with 0.4 mL of 50% test substance in Alembicol D and or neat test substance, as supplied. The patches remained in place for 24 hours under occlusion and were then removed. Slight to well-defined erythema with dryness and sloughing of the epidermis was observed in both the control and test animals when Bevilite 62-L was applied either neat or at 50% concentration in Alembicol D. These results were considered to be inconclusive. The animals were therefore re-challenged on the opposite flank following a 1 week rest period with 10% or 20% test substance in Alembicol D. Slight irritation with localized dryness and sloughing of the epidermis was observed during the second challenge, but the reactions observed in the test animals were somewhat less marked than in the controls. It was concluded that Bevilite 62-L was not a dermal sensitizer under the conditions of the study.

In a maximization test (Biogir SA, 1993b), 15 female Hartley albino guinea pigs were induced topically (Day 0 and Day 7) with 100 % Hydrogral G5 (Resin acids and rosin acids, hydrogenated, esters with glycerol). On Day 29, the test animals, along with a group of 15 female control animals previously not induced with the test material, were challenged topically for 24 hours with concentrations of 50 and 25% of the test material in paraffin oil. These concentrations were equal to the MNIC and 1/2 of the MNIC. Skin examinations at 24 and 48 hours after the completion of the challenge exposure indicated no signs of a skin reaction for the control or treated group of animals. The test substance was not therefore considered to be a skin sensitizer in female guinea pigs.

In another maximization test, this time performed using Foral 85 (Resin acids and rosin acids, hydrogenated, esters with glycerol) as the test substance, five guinea pigs/sex were induced via intradermal injections of the following: 0.1 mL of FCA/water emulsion without the test substance, 0.1 mL of the test substance/corn oil (at 10%), and 0.1 mL of the test substance/corn oil in the FCA/water emulsion (at 5%) (Consumer Product testing Co, 1997a). Since no irritation was observed, six days after intradermal injections, the animals were exposed topically to a 10% solution of sodium lauryl sulfate to elicit an irritation response. The following day, 25% Foral 85 in petroleum jelly was topically applied for 24 hours. Two weeks after the induction period, the animals were challenged with 0.4 mL of a 25% solution of the test substance/petroleum jelly under occlusive conditions. The test material remained in place for 24 hours under occlusion and for 21 hours under open conditions, after which the remaining test substance was removed with an ethanol wipe. Three hours later, each site was observed and scored for erythema and edema. An additional observation was made 24 hours later. No irritation was seen in any animal under the conditions of the study. Based on the results of this study, the test substance did not exhibit a potential for dermal sensitization.

In a skin sensitization study performed on HARRPA Synthesised Product No. 1 - Glycerol Ester of Tall Oil Rosin (Resin acids and rosin acids, tall-oil, esters with glycerol, chemically equivalent to Resin acids and rosin acids, esters with glycerol), 20 female guinea pigs were induced by intradermal injection of the following: Freund's Complete Adjuvant diluted with an equal volume of olive oil, test substance 10% (w/v) in olive oil, and test substance 10% (w/v) in a 1:1 mixture of Freund's Complete Adjuvant and olive oil (Central Toxicology Laboratory, 1997a). One week later, a 75% solution (w/v) of test substance in white petrolatum was applied under occlusion to the skin of each guinea pig. During the induction phase, ten control animals were treated the same as the test animals except that they received olive oil or white petrolatum in place of the test substance. Fifteen days after the induction period, all test and control animals were challenged with 10, 25, and 50% (w/v) dilutions of the test substance in white petrolatum or white petrolatum, only. The challenge patches remained in place for 24 hours under occlusion, and then the dressings were removed. Animals in most groups exhibited a mild irritation response, characterized by scattered mild redness, 24 and 48 hours after patch removal. These responses were not statistically significant and the sample was not considered a skin sensitizer in guinea pigs under the conditions of the test. In a second skin sensitization study using this same sample and following an induction protocol identical to that described above, guineas pigs were challenged two weeks post- induction with 10, 25, 50, and 75% (w/v) of test substance in olive oil (Central Toxicology Laboratory, 1997b). Some animals in the 50% and 75% groups elicited a mild irritation response, 24 and 48 hours after patch removal, characterized by scattered mild redness. These responses were not statistically significant and confirmed that the sample was not a skin sensitizer in guinea pigs under the conditions of the test.

In a guinea pig maximization test using Dertoline CG N8 (Resin acids and rosin acids, esters with glycerol), 15 guinea pigs/group were intradermally injected with Freund's adjuvant, and exposed topically to 0.5 g of test substance under semi-occlusion (Biogir SA, 1993a). On Day 7, the animals were exposed topically to 0.5 g of undiluted test substance under semi-occlusion for 48 hours. Two weeks post- induction period, the animals were challenged with 6.25 and 12.5% solutions of the test substance in paraffin oil. No irritation or sensitisation response was observed at any timepoint in any animal. Under the conditions of the study, Dertoline CG N8 was not a skin sensitizer.

In a guinea pig maximization test on Bevipale 85 (Resin acids and rosin acids, esters with glycerol), 20 female guinea pigs were intradermally injected with the following: Freund's complete adjuvant diluted with an equal volume of water for irrigation, test substance 7.5% in Alembicol D, and test substance 7.5% in a 50:50 mixture of Freund's complete adjuvant and Alembicol D (Huntingdon Research Centre Ltd, 1992b). Six days after the intradermal injections, the same interscapular area was clipped and shaved free of hair and the site was pre-treated by gentle rubbing with 0.2 mL per site of 10% sodium lauryl sulphate in petrolatum. The next day 0.4 mL of Bevipale 85, 83.3% in Alembicol D, was topically applied and remained in contact with the skin for 48 hours. Two weeks after the induction period, the animals were challenged with 0.4 mL of either 83.3% or 41.65% test substance in Alembicol D for 48 hours under occlusion. Dermal irritation, characterized as slight to well defined erythema, was observed during the first 48 hours in both control and test substance-treated animals challenged with 83.3% Bevipale 85 in Alembicol D. All animals appeared normal after 72 hours. Since there was no significant difference in incidence or intensity of response between control and test substance-treated animals, under the conditions of the study, Bevipale 85 was not considered to be a dermal sensitizer in guinea pigs.

In a guinea pig maximization test using Bevilite 62-107 (Resin acids and rosin acids, esters with pentaerythritol), 20 female guinea pigs were intradermally injected with the following: Freund's complete adjuvant diluted with an equal volume of water for irrigation, test substance 5% (v/v) in 5% acetone in Alembicol D, and test substance 5% (v/v) in a 50:50 mixture of Freund's complete adjuvant and 5% acetone in Alembicol D (Huntingdon Research Centre Ltd, 1990a). Seven days after the intradermal injections, 0.4 mL of a 60% solution of the test substance in acetone was topically applied and held in contact with the skin under occlusion for 48 hours. Two weeks after the induction period, the animals were challenged at two locations with 0.2 mL of Bevilite 62-107, using a 60% solution in acetone and a 30% solution in acetone. The patches remained in place for 24 hours under occlusion. No reaction indicative of sensitization was observed during the challenge phase of the study indicating that the test substance was not a dermal sensitizer.

In a guinea pig maximization test employing Bevitack 105/20 (Resin acids and rosin acids, esters with pentaerythritol), 20 female guinea pigs were intradermally injected with the following: Freund's complete adjuvant diluted with an equal volume of water for irrigation, test substance 7.5% (w/w) in liquid paraffin, and test substance 7.5% (w/w) in a 50:50 mixture of Freund's complete adjuvant and liquid paraffin (Huntingdon Research Centre Ltd, 1992c). Six days after intradermal injections, the animals were exposed topically to a 10% solution of sodium lauryl sulfate. The following day, 0.4 mL test substance (76.9% in liquid paraffin) was topically applied and held in contact with the skin for 24 hours. Two weeks after the induction period, the animals were challenged with 0.2 mL of either Bevitack 105/20 76.9% (w/w) in liquid paraffin or Bevitack 105/20 38.45% (w/w) in liquid paraffin. The challenge patches remained in place for 24 hours under occlusion. Mechanical damage to the skin, caused by the stickiness of the test substance stripping the hair and skin, was observed in control and test animals following removal of the bandages. Since the test sites could not be adequately evaluated, the animals were rechallenged after a 1 week rest period using test substance at 20 and 10% (w/w) in liquid paraffin. Irritation was again observed following the second challenge, but it was of a magnitude which allowed for evaluating the sensitization potential of the test substance. Skin reactions in 2/20 of the test group were rated as "inconclusive", defined as a reaction slightly more marked or persistent (though not distinguishable from) the maximum reactions seen for the control animals; responses observed in the remaining eighteen test animals were similar to the controls. Based on these results, the test substance was not considered to possess a potential for causing dermal sensitization.

In a guinea pig maximization test on HARRPA 2 (Resin acids and rosin acids, esters with pentaerythritol), 20 male guinea pigs were intradermally injected with the following: Freund's complete adjuvant diluted with an equal volume of sterile saline, test substance 10% (v/v) in coconut oil, and test substance 10% (v/v) in a 1:1 mixture of Freund's complete adjuvant and sterile saline (Scantox DK, 1997a). Six days later a 50% solution of the test substance in coconut oil was applied under occlusion to the skin of each guinea pig. Two weeks after the induction period, the animals were challenged with either 25 or 50% concentrations of HARRPA 2 for 24 hours under occlusion. No dermal irritation or sensitization was observed during either the induction or challenge phase of the study. The results indicate that the test substance was not a potential skin sensitizer.

In a guinea pig maximization test, the dermal sensitisation potential of the test material Sylvalite RE 80 HP (Resin acids and Rosin acids, esters with trimethylolpropane) was evaluated in albino guinea pigs (Covance Laboratories, Inc., 2001). The test material was ground to a powder and administered as a 0.4 g dose (moistened with mineral oil) to each animal in the test group during the naive- application induction phase of the study. The test material produced very faint to moderate erythema reactions (scores of 0.5 to 2.0) in the test and naive control animals when administered as 50% w/v mixture in mineral oil at the initial challenge application.

 

None of the initial challenge reactions in the test group exceeded the highest naïve control reaction. Very faint to faint erythema reactions (score of 0.5 – 4 animals, score 0.1 – 1 animals) were observed in the test animals and very faint erythema reactions were seen in 2 of the 10 additional naïve control animals when the test material was applied as 25% w/v mixture in mineral oil at the second challenge application. Due to the level of irritation observed in both groups during the challenge phase, none of the second challenge reactions in the test group are considered to be sensitization reactions.

 

The reactions observed at challenge are most likely irritation reactions. Based on the challenge dose results, the test material was not considered to be a dermal sensitizer.

 

In another guinea pig maximisation test (Huntingdon Research Centre, 1987), the intradermal and topical irritancy of a range of dilutions of ester of tall oil rosin (Resin acids and Rosin acids, esters with trimethylolpropane) was investigated to identify the irritant test substance concentrations suitable for the induction phase of the main study and the non – irritant concentrations by the topical route of administration for the challenge phase.

 

During induction, the test material was administered as an intradermal injection (7.5% w/w in liquid paraffin and 7.5% w/w in a 50:50 mixture of Freund’s complete adjuvant and liquid paraffin. One week after the injection, the same intrascapular area was clipped and shaved free of hair and a 2 x 4 cm patch of Whatman No. 3 paper saturated with ester of tall oil rosin (30% w/w in liquid paraffin) was placed on the skin and covered by impermeable plastic adhesive tape. This in turn was firmly secured by elastic adhesive bandage wound around the torso of the animal and fixed with impervious plastic adhesive tape. The dressing was left in place for 48 hr. During the induction period the control animals were treated similarly to the test animals with exception that the test compound was omitted from the intradermal injections and topical application.

 

The test and control animals were challenged topically two weeks after the induction period using ester of tall oil rosin 10% and 5% w/w in liquid paraffin. The patches were sealed to the flank for 24 hours under strips covered by Elastoplast wound around the trunk and secured with Sleek. The challenge sites were evaluated 24, 48 and 72 hours after removal of the patches.

 

The dermal reactions in the test animals elicited by the challenge application were comparable to the findings simultaneously observed in control animals. Based on the results observed, there was no evidence of delayed contact hypersensitivity seen in 18 animals.  

Human data

In a human repeat insult patch test (HRIPT; Consumer Product Testing Co., 1998a) conducted according to generally accepted international methods for the testing of skin sensitization potential in humans, there was no evidence of irritation or a sensitization response in 209 male and female test subjects repeatedly exposed to 0.2 grams of Resin acids and rosin acids, hydrogenated, Me esters under occluded patch for 24-hours. The study involved 9 induction exposures over a 3 week period followed by a challenge exposure after a 2 -week rest period.

In a Human Repeat Insult Patch Test conducted according to generally accepted international methods for the testing of skin sensitization potential in humans, there was no evidence of irritation or a sensitization response in 202 male and female test subjects repeatedly exposed to 0.2 grams of Foral 85 (Resin acids and rosin acids, hydrogenated, esters with glycerol) under occluded patch for 24 hours for a total of 10 applications (Consumer Product testing Co, 1997c). After a rest period of 2 weeks following the last application, the panelists were patched with the test substance on both the original site and a naïve site (volar forearm) to determine the sensitization potential of the test material. Under the conditions of the study, the test substance did not demonstrate a potential for dermal irritation and/or sensitization.

In a human patch test using the Schwartz Patch Test method, 200 volunteers were exposed to Ester Gum 8D and Polypale Ester 10 (Resin acids and rosin acids, esters with glycerol) for five days (Industrial Toxicology Laboratory, 1954). After a 2 week rest period, all panelists were rechallenged for 24 hours. Skin reactivity was recorded immediately after patch removal as well as 24 hours after patch removal. No reactions were noted in either the irritation or sensitization portions of the test. In a second study, a Human Repeat Insult Patch Test, 50 panelists were exposed to Ester Gum 8D and Polypale Ester 10 for a total of fifteen patch inductions every other day. Again, all panelists were negative in both the irritation and sensitization portions of the test with the exception of a solitary and transient (1+) irritant reaction noted on one male panelist during the course of the study with Ester Gum 8D. Under the conditions of the study, Ester Gum 8D and Polypale Ester 10 did not indicate a potential for dermal irritation and/or sensitization.

In a human repeat insult patch test, 55 panellists were exposed to Pentalyn H (rosin) (Resin acids and rosin acids, hydrogenated, esters with pentaerythritol) at 0.5 mL (50% Pentalyn H in 50% mineral oil) under semi-occlusion for three 24 hour periods per week for three weeks (Hill Top Research Inc., 1960). After 24 hours of exposure, the subjects removed the patches, and 48-72 hours after patch application, the sites were graded for irritation. After a rest period of 2 weeks, the panellists were patched on both the original and naïve site with the test substance to determine sensitization potential. No effects related to the test substance were observed in any individual during the initial three week irritation screening phase. During the last week of the study when sensitization potential was determined, no panellists showed any signs of irritation or sensitization to the test material. The results of this study indicate that the test substance was neither irritating nor a dermal sensitizer.


Short description of key information:
Not sensitising in humans, mouse (LLNA) or guinea pig (Maximization Test)

Justification for selection of skin sensitisation endpoint:
Information is available on the sensitisation potential of Resin acids and rosin acids, hydrogenated, Me esters, Resin acids and rosin acids, esters with triethylene glycol, 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, hydrogenated, esters with pentaerythritol. The results demonstrate that Rosin esters are not sensitising in humans, mouse (LLNA) or guinea pig (Maximization Test).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Migrated from Short description of key information:
Not expected to induce or elicit respiratory sensitization based on an absence of skin sensitization potential

Justification for selection of respiratory sensitisation endpoint:
Rosin esters are not expected to cause or elicit respiratory based upon an absence of skin sensitisation potential and a lack of chemical or structural alerts.

Justification for classification or non-classification

Not classified for skin sensitization 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).