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Description of key information

Several key guideline (OECD 408, 414, 421, & 422 ) studies that investigated the repeated dose toxicity potential of Rosin; Rosin, hydrogenated; Rosin, oligomers; and Rosin, reaction products with formaldehyde following oral dietary exposure in rats are available. The results are summarized below:

OECD 408

1) Rosin (CAS# 8050 -09 -7): The systemic toxicity NOAEL was determined to be 5000 ppm (equivalent to a mean achieved dosage of 335.2 mg/kg bw/day for males and 401.2 mg/kg bw/day for females) based on reduced body weight gains in animals of either sex exposed to 7500 ppm.

2) Rosin, reaction products with formaldehyde (CAS# 91081 -53 -7): The NOAEL for systemic toxicity of Rosin, reaction products with formaldehyde was considered to be 3000 ppm (equivalent to mean achieved dosages of approximately 213.1 mg/kg bw/day or 255.2 mg/kg bw/day for males and females, respectively), based on the effects on body weight, body weight gain and, to a lesser extent, food consumption, observed among females exposed to diets containing 7500 ppm of the test material for ninety days.

3) Rosin, hydrogenated (CAS# 65997 -06 -0): Based on a lack of adverse treatment-related effects observed at the highest concentration tested, the systemic toxicity NOAEL for Rosin, hydrogenated was determined to be 6000 ppm for either sex (equivalent to a mean achieved dosage of 334.5 mg/kg bw/day for males and 399.8 mg/kg bw/day for females).

OECD 414

1) Rosin (CAS# 8050 -09 -7): The systemic toxicity NOAEL for Rosin was determined to be 2500 ppm (equivalent to a mean achieved dosage of 199.3 mg/kg bw/day) based on lower maternal body weight gain during gestation and an initial effect on food consumption at 7500 ppm and lower maternal body weight gain at 5000 ppm.

OECD 421

1) Rosin (CAS# 8050 -09 -7): The systemic toxicity NOAEL for Rosin was determined to be 1000 ppm in males (equivalent to 84 mg/kg bw/d) and 3000 ppm in females (equivalent to 309 mg/kg bw/d) based upon reduced feed consumption and lower weight gain in animals consuming higher dietary concentrations of the test material.

OECD 422

1) Rosin (CAS# 8050 -09 -7):

In a key combined repeated dose, reproductive/developmental toxicity screening study (Harlan Laboratories Ltd, 2015a), the sytemic toxicity NOAEL for Tall oil rosin was determined to be 5000 ppm.

In another key combined repeated dose, reproductive/developmental toxicity study (Harlan Laboratories Ltd., 2014a), the systemic toxicity NOAEL for Gum Rosin was determined to be 2500 ppm. A NOEL (No Observed Effect Level) for general toxicity could not be established due to effects on body weights at all dose levels in females during the lactation period.

2) Rosin, reaction products with formaldehyde (CAS# 91081 -53 -7): The systemic toxicity NOAEL for Rosin, reaction product with formaldehyde was determined to be 10000 ppm and the NOEL was established at a concentration of 1000 ppm.

3) Rosin, hydrogenated (CAS# 65997 -06 -0): The systemic toxicity NOAEL for Rosin, hydrogenated was determined to be 3000 ppm. Based on the histopathological changes observed in adrenal glands, no NOEL for systemic toxicity was established for females whereas for males it was at the dose level of 1000 ppm.

4) Rosin, oligomers: The systemic toxicity NOAEL for Rosin, oligomers in male rats was determined to be 7500 ppm, based on statistically significant body weight and body weight gain effects observed at the 15000 ppm concentration level. The systemic toxicity NOAEL for female rats was determined to be 3000 ppm, based on effects on body weight and body weight gain in females exposed to the test material at 7500 and 15000 ppm.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Key information is available from guideline (OECD 408, 414, 421, & 422 ) studies that have investigated the repeated dose oral toxicity of Rosin; Rosin, hydrogenated; Rosin, oligomers, and Rosin, reaction products with formaldehyde following dietary administration to rats.

Information also exists for Rosin; Rosin oligomers; and Rosin, hydrogenated when tested in rats and dogs using oral exposure regimes of equivalent duration. However, this supporting data is from Klimisch 3 studies (not reliable) conducted by Industrial Bio-test Laboratories Inc. and were performed prior to the introduction of OECD testing protocols and the introduction of GLP with the extent of information reported deviating from that expected of a modern guideline investigation. Results from these investigations are summarised below and included in the dossier solely for the purpose of including all available data.

Rosin

In a key oral repeat dose toxicity study (Envigo Research Limited, 2017a), the test material (Rosin, CAS# 8050-09-7) was administered continuously in the diet of three groups, each composed of ten male and ten female Wistar Han™:RccHan™:WIST strain rats, for ninety consecutive days, at dietary concentrations of 2500, 5000 or 7500 ppm (equivalent to a mean achieved dosage of 174.1, 335.2 or 510.1 mg/kg bw/day for males and 196.4, 401.2 or 596.2 mg/kg bw/day for females). A control group of ten males and ten females were fed basal laboratory diet.

 

The continuous dietary administration of the test material to rats, at dietary concentrations of 2500, 5000 and 7500 ppm for ninety consecutive days, resulted in reduced body weight gains in animals of either sex exposed to 7500 ppm and microscopic adrenal changes in animals of either sex exposed to 7500 and 5000 ppm. The No Observed Effect Level (NOEL) for both sexes was therefore considered to be 2500 ppm (equivalent to a mean achieved dosage of 174.1 mg/kg bw/day for males and 196.4 mg/kg bw/day for females). The microscopic adrenal changes (hypertrophy of the zona glomerulosa) identified in animals of either sex exposed to 7500 or 5000 ppm were mild. The changes were not considered to have affected normal electrolyte regulation and did not appear to have an effect on homeostatic control. Therefore, they were not considered to have had adverse consequences for the organ or the body. For this reason, 5000 ppm (equivalent to a mean achieved dosage of 335.2 mg/kg bw/day for males and 401.2 mg/kg bw/day for females) was considered to be the “No Observed Adverse Effect Level” (NOAEL) systemic toxicity.

In a key pre-natal developmental toxicity study (Envigo Research Limited, 2017b), the test material (Rosin, CAS# 8050-09-7) was administered by continuous dietary admixture to three groups each composed of twenty-four time mated Sprague-Dawley Crl:CD®(SD) IGS BR strain rats, between gestation days 3 and 19 (inclusive) at dietary concentrations of 2500, 5000, or 7500 ppm (equivalent to mean achieved dosages of 199.3, 387.2 or 561.1 mg/kg bw/day respectively). The oral administration of the test material to pregnant rats by continuous dietary exposure was associated with lower maternal body weight gain during gestation and an initial effect on food consumption at 7500 ppm and lower maternal body weight gain at 5000 ppm. No similar effects were apparent at 2500 ppm (equivalent to a mean achieved dosage of 199.3 mg/kg bw/day) which was considered to represent the No Observed Adverse Effect Level (NOAEL) for the pregnant female. In-utero survival of the developing conceptus was unaffected by maternal exposure at 7500 ppm, although reduced foetal and placental weights indicated an adverse effect on foetal growth. The absence of any structural defects indicated that development per se was unaffected at this dietary exposure level. At 5000 or 2500 ppm no adverse treatment-related changes were detected in the offspring parameters measured or on embryofoetal development. The ‘No Observed Adverse Effect Level’ (NOAEL) for foetal developmental toxicity was therefore considered to be 5000 ppm (equivalent to a mean achieved dosage of 387.2 mg/kg bw/day).

In a key combined repeated dose, reproductive/developmental toxicity screening study (Harlan Laboratories Ltd, 2015a), the test material (Tall oil rosin, CAS# 8050-09-7) was administered daily in dietary mixtures at concentrations of 0, 2500 ppm (males - 160 mg/Kg bw/day Pre-Pairing and 136.4 mg/Kg bw/day Post-Pairing; females - 189 mg/Kg bw/day Pre-Pairing; 182.8 mg/Kg bw/day Gestation; and 241.1 mg/K bw/day Lactation), 5000 ppm (males - 301.5 mg/Kg bw/day Pre-Pairing and 276.5mg/K bw/day Post-Pairing; females – 356.1 mg/Kg bw/day Pre-Pairing; 377.3 mg/Kg bw/day Gestation; and 572.7 mg/K bw/day Lactation), or 10000 ppm (males - 496.4 mg/Kg bw/day Pre-Pairing and 585.5 mg/K bw/day Post-Pairing; females – 612.9 mg/Kg bw/day Pre-Pairing; 772.2 mg/Kg bw/day Gestation; and 1227.9 mg/K bw/day Lactation) to male rats for 42 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. Based on observations in the study, the NOEL (No Observed Effect Level) was established at the concentration level of 2500 ppm and the NOAEL (No Observed Adverse Effect Level) was established at 5000 ppm for general toxicity. For reproductive and developmental toxicity, the NOEL was established at 5000 ppm whereas the NOAEL was established at the concentration level of 10000 ppm, the highest concentration tested in the study.

In another key combined repeated dose, reproductive/developmental toxicity study (Harlan Laboratories Ltd., 2014a), Gum Rosin (CAS# 8050-09-7) was administered to rats (12/sex/dose) in dietary mixtures at concentrations of 0, 2500, 5000, and 10000 ppm for a period of 50 days for male rats and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum (at least 36 days, up to 53 days). A NOEL (No Observed Effect Level) for general toxicity could not be established due to effects on body weights at all dose levels in females during the lactation period. The NOAEL (No Observed Adverse Effect Level) for general toxicity was established at the dose level of 2500 ppm. The NOEL and the NOAEL for reproduction/developmental toxicity were established at 5000 ppm.

In a reproductive/developmental toxicity screening study (Inveresk Research, 2003a), 10 rats/sex/group were exposed to Gum Rosin (CAS# 8050-09-7) at dose concentrations of 0, 1000, 3000, or 10000 ppm for 41-45 days (females) or 30 days (males) in the diet. Treatment with Gum Rosin at 10000 ppm was associated with reduced weight gain/weight loss and reduced food consumption in the parental generation and a slight decrease in the mean number of implantation sites resulting in a subsequent slight reduction in litter size. Body weight gain reductions were also observed in males exposed to 3000 ppm Gum Rosin. Adverse effects in the F1 pups were limited to slightly reduced litter and pup weights. Based on the results of the present study, the NOAEL for  reproductive/developmental toxicity in Sprague-Dawley rats was considered to be 3000 ppm for males (equivalent to 248 mg/kg bw/d) and females (equivalent to 309 mg/kg bw/d) and the NOAEL for subchronic toxicity was considered to be 1000 ppm in males (equivalent to 84 mg/kg bw/d) and 3000 ppm in females (equivalent to 309 mg/kg bw/d) based upon reduced feed consumption and lower weight gain in animals consuming higher dietary concentrations of the test material.

In a subchronic dietary toxicity study, Gum Rosin XA 10-59 (Rosin) was administered to 10 rats/sex/group at target concentrations of 0.010, 0.050, 0.20, 1.0, or 5.0% continuously for 90 days (Industrial Bio-Test Laboratories Inc., 1960c; Klimisch = 3).

Toxicity was limited to complete mortality within the high dose group (5.0%), statistically significantly decreased body weights in the 1.0% group, and organ weight changes in various test substance groups. The NOAEL was determined to be 0.2% for both male and female rats.

 

In a chronic toxicity study, Gum Rosin (Rosin) was administered to 30 rats/sex/group in the diet at target concentrations of 0.050 or 1.0% ad libitum for up to 2 years (Industrial Bio-Test Laboratories Inc., 1962h; Klimisch = 3). Effects related to the administration of Gum Rosin were limited to statistically significantly lower body weights in animals exposed to 1.0% of the test substance at both 12 and 24 months of exposure. The NOAEL for systemic toxicity was determined to be 1.0% in the diet for males and females. The overall NOAEL for the study was 0.05% in the diet, based on reduced body weights attributed to the palatability of the test substance.

 

In a chronic dietary toxicity study, Gum Rosin (Rosin) was administered to 3 Beagle dogs/sex/group at target concentrations of 0.050 or 1.0% daily for 2 years (Industrial Bio-Test Laboratories Inc., 1962g; Klimsich = 3). All animals survived to the end of the study and no toxicity related to the administration of Gum Rosin was observed for any study parameter in any animal. The NOAEL for chronic systemic toxicity was determined to be 1.0% for male and female Beagle dogs.

Rosin, hydrogenated

In a key sub-chronic toxicity study (Envigo Research Limited, 2016a), the test material (Rosin, Hydrogenated; CAS# 65997-06-0) was administered by continuous dietary admixture to groups of male and female WistarHan™:RccHan™:WIST strain rats(10/sex/concentration), for ninety consecutive days, at dietary concentrations of 1000 and 2000 ppm for the low and intermediate exposure groups (equivalent to mean achieved dosages of 64.5 and 133.3 mg/kg bw/day for males and 78.5 and 156.4 mg/kg bw/day for females). For the high exposure group, rats were initially fed diet containing 4000 ppm for five weeks followed by 6000 ppm for the remainder of the study (equivalent to mean achieved dosages of 334.5 mg/kg bw/day for males and 399.8 mg/kg bw/day for females). A control group of ten males and ten females were fed basal laboratory diet. The No Observed Adverse Effect Level (NOAEL) was determined to be 6000 ppm for either sex (equivalent to a mean achieved dosage of 334.5 mg/kg bw/day for males and 399.8 mg/kg bw/day for females).

In a key combined repeated dose, reproductive/developmental toxicity study (Harlan Laboratories Ltd., 2015b), the test material (Rosin, hydrogenated; CAS# 65997-06-0) was continuously administered in feed to rats (12/sex/concentration) at concentrations of 0, 1000, 3000, and 10000 ppm. The test material was administered to male rats for 43 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. Based on the histopathological changes observed in adrenal glands, no NOEL (No Observed Adverse Effect Level) for systemic toxicity was established for females whereas for males it was at the dose level of 1000 ppm. The NOAEL (No Observed Adverse Effect Level) was established at 3000 ppm. For reproduction and developmental toxicity, the NOEL was established at the dose level of 3000 ppm whereas the NOAEL was at 10000 ppm, the highest dose level used in the study.

In a chronic dietary toxicity study, Staybelite Resin (Rosin, hydrogenated) was administered to 30 rats/sex/group at target concentrations of 0.050, 0.20 or 1.0% continuously for 2 years (Industrial Bio-Test Laboratories Inc., 1962b; Klimisch = 3). Toxicity was limited to statistically significantly decreased body weights in animals exposed to 1.0% of the test substance at the interim sacrifice but not the terminal sacrifice. Some statistically significantly altered organ weights were noted in females, were not dose-dependent and not supported by histopathological examination. The NOAEL for chronic systemic toxicity was determined to be 1.0% for males and females.

 

In a chronic dietary toxicity study, Staybelite Resin (Rosin, hydrogenated) was administered to 3 Beagle dogs/sex/group at target concentrations of 0.050 or 1.0% daily for 2 years (Industrial Bio-Test Laboratories Inc., 1962a; Klimisch = 3). All animals survived to the end of the study and no toxicity was observed for any study parameter in any animal. The NOAEL for chronic systemic toxicity was determined to be 1.0% for both males and females.

Rosin, reaction products with formaldeyde

In a key sub-chronic oral repeated dose toxicity study (Envigo Research Limited, 2017b), the test item (Rosin, reaction products with formaldehyde; CAS# 91081-53-7), was administered by continuous dietary admixture to three groups, each of ten male and ten female Wistar Han™:RccHan™:WIST strain rats, for ninety consecutive days, at dietary concentrations of 1000, 3000 and 7500 ppm (equivalent to a mean achieved dosage of 68.9, 213.1 and 509.2 mg/kg bw/day for males and 84.0, 255.2 and 644.6 mg/kg bw/day for females respectively). A control group of ten males and ten females were treated with basal laboratory diet.

 

Based on the effects on body weight, body weight gain and, to a lesser extent, food consumption, observed among females exposed to diets containing 7500 ppm of the test material, the No Observed Adverse Effect Level (NOAEL) for systemic toxicity of Rosin, reaction products with formaldehyde (CAS 91081-53-7) in this Ninety Day Toxicity study was considered to be 3000 ppm (equivalent to mean achieved dosages of approximately 213.1 mg/kg bw/day or 255.2 mg/kg bw/day for males and females, respectively). As an initial transient effect on body weight and food consumption (which may reflect palatability of the diet formulations) was apparent at 1000 ppm, the No Observed Effect Level (NOEL) for systemic effects could not be established.

In a key combined repeated dose, reproductive/developmental toxicity study (Harlan Laboratories Ltd., 2015c), the test material (Rosin, reaction product with formaldehyde, CAS # 91081-53-7) was administered daily in dietary mixtures to RccHanTM: WIST(SPF) rats (12/sex/concentration) at concentrations of 0, 1000, 3000 and 10000 ppm. The test item was administered to male rats for 43 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. Based on the results of this study, the NOAEL (No Observed Adverse Effect Level) for systemic toxicity was established at a concentration of 10000 ppm and the NOEL (No Observed Effect Level) was established at a concentration of 1000 ppm. The NOAEL and NOEL for reproduction/ developmental toxicitywere established at a concentration of 10000 ppm, the highest dose level used in the study.

Rosin oligomers

In a key combined repeated dose, reproductive/developmental toxicity study (Harlan Laboratories Ltd., 2014b), the test material (Rosin, oligomers; CAS # 65997-05-9) was administered to rats (12/sex/concentration) in dietary mixtures at concentrations of 0, 3000, 7500 and 15000 ppm. The test material was continuously administered to male rats for 43 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum (up to 55 days). Based on the results of this study, the NOAEL for systemic toxicity in male rats was established at 7500 ppm, based on statistically significant body weight and body weight. gain effects observed at the 15000 ppm concentration level. The systemic toxicity NOAEL for female rats was determined to be 3000 ppm, based on effects on body weight and body weight gain in females exposed to the test material at 7500 and 15000 ppm. The NOEL and the NOAEL for reproductive/developmental toxicity was determined to be 3000 ppm.

In another subchronic dietary toxicity study, Poly-Pale Resin (Rosin, Oligomers) was administered to 10 rats/sex at a concentration of 1.0% ad libitum for 90 days (Hazelton Laboratories Inc., 1965a; Klimisch = 2). A control group with 10 rats/sex was provided the diet with the vehicle but not the test material for 90 days. Test material-related effects were limited to a statistically significant decrease in body weight in females only, a statistically significant increase in thyroid organ weights in males only, significant increases in adrenal and thyroid-to-body weight ratios in females only, and significantly higher organ-to-body weight ratios for liver, spleen and kidneys in both sexes. Most of these changes were attributed to the slightly reduced body weights in test animals and were not considered evidence of significant target organ toxicity because there were no gross or microscopic findings observed in either sex at necropsy. In addition, there were no effects on clinical chemistry parameters. Under the conditions of this study, the NOAEL was therefore 1% in the diet.

In a subchronic toxicity study, Poly-Pale Resin (Rosin, oligomers) was administered to 3 dogs/sex at dietary concentrations of 0% and 1.0% continuously for 90 days (Hazelton Laboratories Inc., 1965b; Klimisch = 2). Effects of the test substance included borderline increases in alkaline phosphatase levels, slight pale, yellow-brown discoloration of the liver in one animal, and microscopic alterations to the testes of one animal that resulted in abnormal spermatogenesis. Under the conditions of this study, the NOAEL for systemic toxicity was less than 1.0% for both male and female dogs.

In a subchronic dietary toxicity study, Dymerex Resin (Rosin, oligomers) was administered to 10 rats/sex/group at target concentrations of 0.010, 0.050, 0.20, 1.0, or 5.0% continuously for 90 days (Industrial Bio-Test Laboratories Inc., 1960a; Klimisch = 3). Test material related effects were limited to reduced body weights and lower food consumption. This, in turn, also affected several organ-to-body weight ratios. The reduction in food consumption and weight gain were likely due to palatability issues which occurred during the first two weeks of the study. The NOAEL for systemic toxicity was determined to be 1% for males and 0.20% for females. However, based on an absence of gross or microscopic findings at necropsy, no significant target organ toxicity was identified in either sex at up to 5.0% Dymerex Resin in the diet.

 

In a subchronic toxicity study, Poly-Pale Resin (Rosin, oligomers) was administered to 10 rats/sex/group at target dietary concentrations of 0.010, 0.050, 0.20, 1.0, or 5.0% continuously for 90 days (Industrial Bio-Test Laboratories Inc., 1960b; Klimisch = 3). Eight of 20 animals in the 5.0% dietary group died prior to study termination. For survivors, treatment-related toxicity was limited to reduced body weights, reduced food consumption, and organ weight changes to the heart (males and females), liver (females), kidney (females) and spleen (females). The NOAEL for systemic toxicity was determined to be 0.20% for male rats and 0.050% for female rats. However, based on an absence of gross or microscopic findings at necropsy, no significant target organ toxicity was identified in either sex at up to 5.0% Poly-Pale Resin in the diet.

 

In a chronic dietary toxicity study, Dymerex Resin (Rosin, oligomers) was administered to 30 rats/sex/group at target concentrations of 0.050 or 1.0% continuously for 2 years (Industrial Bio-Test Laboratories Inc., 1962c; Klimisch = 3). Toxicity was limited to decreased male body weights at the interim sacrifice in animals administered the test substance at a dietary level of 1.0% but not at the terminal sacrifice, and statistically significant absolute liver weight changes in females. The changes in organ weights were not supported by the histopathological examination and the male body weights at the interim sacrifice returned to values similar to control at the terminal sacrifice.  The NOAEL for chronic toxicity was determined to be 1.0% for male and female rats.

 

In a chronic dietary toxicity study, Poly-Pale Resin (Rosin, oligomers) was administered to 30 rats/sex/group at target concentrations of 0.050 or 1.0% continuously for 2 years (Industrial Bio-Test Laboratories Inc., 1962e; Klimisch = 3). Test material related toxicity was limited to the 1% dietary group and included statistically significant decreased body weights in both sexes of animals at the interim sacrifice with female body weights remaining statistically lower at the terminal sacrifice; an increase in the liver-to-body weight ratio in female rats; and a significant decrease in heart weight, heart-to-body weight, and heart-to-brain weight ratios for both sexes. The changes in organ weights occurred with no corresponding gross and histopathological effects. Body weight reductions were thought to be related to test substance palatability based on the decrease in total food consumption observed in both sexes at the 52-week observation. The NOAEL for chronic toxicity was determined to be 0.050% for male and female rats. 

 

In a chronic dietary toxicity study, Dymerex Resin (Rosin, oligomers) was administered to 3 dogs/sex/group at target concentrations of 0.050 or 1.0% daily for 2 years (Industrial Bio-Test Laboratories Inc., 1962d; Klimisch = 3). All animals survived to the end of the study and no significant toxicity was observed in any study parameter for the treated animals. The NOAEL for chronic toxicity was determined to be 1.0% for male and female Beagle dogs.

 

In a chronic dietary toxicity study, Poly-Pale Resin (Rosin, oligomers) was administered to 3 dogs/sex/group at target concentrations of 0.050 or 1.0% daily for 2 years (Industrial Bio-Test Laboratories Inc., 1962f; Klimisch = 3). All animals survived to the end of the study and no significant toxicity was observed for any study parameter in any animalThe NOAEL for chronic toxicity was determined to be 1.0% for male and female dogs.

Justification for classification or non-classification

Not classified for specific target organ toxicity – repeated exposure 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).