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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
250 mg/kg bw/day
Additional information

An oral repeated dose/reproductive/developmental screening study conducted with rosin, fumarated was identified; however, no repeated dose toxicity studies were identified for other category substances. Instead, several oral repeated dose/reproductive/developmental screening studies were identified for a rosin adduct ester and a gum rosin were used for read-across purposes because these substances are similar based on their structure and synthetic grounds. All studies were GLP compliant and followed OECD (422 or 421) guidelines. Summaries of the findings are presented below. 

 

Rosin, fumarated was administered in the diet to rats at concentrations of 0, 1000 ppm (males 72-89 mg/kg bw/d; females 79-108 mg/kg bw/d), 3000 ppm (males 221-288 mg/kg bw/d; females 196-292 mg/kg bw/d), and 10,000 ppm (males 651-889 mg/kg bw/d; females 449-995 mg/kg bw/d) (Inveresk Research, 2004). The males were treated for 2 weeks prior to mating, through until necropsy after 4 weeks of treatment. The females were treated for 2 weeks prior to mating, then through mating, gestation and until termination on at least Day 4 of lactation. At 10,000 ppm there was a slight decrease in the mean number of implant sites per pregnancy and a consequent slight reduction in litter size at birth. The slight reduction in litter size between Day1-4 of lactation at 3000 ppm reflects the loss of most pups in one litter. As there were no effects of treatment on litter survival at 10,000 ppm the findings at this level are considered to be incidental. Based on these results, the NOEL for reproductive parameters was considered to be 3000 ppm (males 221-288 mg/kg bw/d; females 196-268 mg/kg bw/d).

 

Results for the supportingrepeated dose/reproductive/developmental screening studies are presented below:

 

In a reproductive/developmental toxicity screening study, 10 rats/sex/group were exposed to Gum Rosin at dose concentrations of 0, 1000, 3000, or 10000 ppm for 41-45 days (females) or 30 days (males) in the diet (Inveresk Research, 2003a). 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 no-observed-effect-level (NOEL) for reproductive/developmental toxicity in Sprague-Dawley rats was considered to be 3000 ppm for males and females and the NOEL for subchronic toxicity was considered to be 1000 ppm in males and 3000 ppm in females based upon reduced feed consumption and lower weight gain in animals consuming higher dietary concentrations of the test material.  

 

In a reproductive/developmental toxicity screening study, 10 rats/sex/group were exposed ad libitum in the diet to rosin pentaerythritol ester (resin acids and rosin acids, esters with pentaerythritol) at dose concentrations of 0, 1000, 5000, or 20000 ppm for 57-60 days (females) or 28 days (males) (Inveresk Research, 2003b). There were no test substance-related effects on reproductive performance of the parental females or on survival and development of the F1 pups. All findings occurred in a non dose-dependent manner, were spurious in nature, or were biologically irrelevant and were not considered related to rosin pentaerythritol ester consumption. The no-observed-adverse-effect-level (NOAEL) for reproductive/developmental toxicity in Sprague-Dawley rats was considered to be 20000 ppm for males and females.  

 

Based on these results, it would be premature to propose a 2-generation reproductive test at this time. The available information will be re-examined once results are available from a pre-natal developmental toxicity test (OECD 414) on Rosin are available, and the scientific need to propose or waive a 2-generation reproductive toxicity test will be determined and communicated to ECHA.


Short description of key information:
One key screening reproductive/developmental was for identified for rosin, fumarated . Several read-across screening reproductive/developmental studies were identified as supporting studies. No reproductive effects were observed in any study.

Effects on developmental toxicity

Description of key information
One key screening reproductive/developmental was identified for rosin, fumarated . No developmental effects were observed.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
250 mg/kg bw/day
Additional information

Rosin, fumarated was administered in the diet to rats at concentrations of 0, 1000 ppm (males 72-89 mg/kg bw/d; females 79-108 mg/kg bw/d), 3000 ppm (males 221-288 mg/kg bw/d; females 196-292 mg/kg bw/d), and 10,000 ppm (males 651-889 mg/kg bw/d; females 449-995 mg/kg bw/d) (Inveresk Research, 2004). The males were treated for 2 weeks prior to mating, through until necropsy after 4 weeks of treatment. The females were treated for 2 weeks prior to mating, then through mating, gestation and until termination on at least Day 4 of lactation. At 10,000 ppm there was a slight decrease in the mean number of implant sites per pregnancy and a consequent slight reduction in litter size at birth. The slight reduction in litter size between Day1-4 of lactation at 3000 ppm reflects the loss of most pups in one litter. As there were no effects of treatment on litter survival at 10,000 ppm the findings at this level are considered to be incidental. Based on these results, the NOEL was considered to be 3000 ppm (males 221-288 mg/kg bw/d; females 196-268 mg/kg bw/d).

A pre-natal developmental toxicity test (OECD 414) on rosin (CAS 8050-09-7), rosin and resin acids, esters with pentaerythritol (CAS 8050-26-8) and rosin and resin acids, fumarated (CAS 65997-04-8) has been proposed to complement this information

Justification for classification or non-classification

Not classified for reproductive or developmental toxicity 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).

Additional information