Overbased reaction products of distilled tall oil and magnesium hydroxide’

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

248 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 089.75 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

Reproductive Toxicity:

In an OECD 422 combined reproductive and systemic toxicity ‘screening’ study (Thorsrud, B., 2011), dermal application of Fatty acids C18-(unsaturated) lithium salts to the dorsal surface of Parental male and female rats at dose levels of 100, 300, and 1000 mg/kg/day did not result in any adverse reproductive effects or any definitive test article-related changes in the development or survival of the offspring.

In addition, results from the clinical pathology evaluations and neurobehavioral testing did not reveal any definitive effects that could be attributed to treatment at the dose levels tested. Test article-related dermal changes were limited to local effects at the test site for Parental animals at 300 and 1000 mg/kg/day, which showed a decreasing trend following cessation of dosing in the designated recovery animals. Microscopic evaluation of the skin at the test site showed minimal to moderate erosion/ulceration, epidermal hyperplasia and exudate, minimal to mild acute to subacute/chronic inflammation and minimal edema, which confirmed the macroscopic findings. At recovery necropsy, test article-related microscopic findings in treated skin of animals at 1000 mg/kg/day were morphologically similar, although they occurred at a lower incidence and severity indicating partial resolution of these findings following the recovery period. Microscopic findings of splenic extramedullary hematopoiesis and thymic lymphoid depletion noted at 1000 mg/kg/day were considered to be secondary adaptive responses to parturition and/or localized dermal effects.

Systemic effects were limited to changes in body weight and organ weight at 1000 mg/kg/day, the highest dose level tested.

In summary, there were no treatment related effects at any dose level on any of the reproductive parameters evaluated in this study. Based on these data, the NOAEL for reproductive toxicity was >1089.75 mg/kg bw/day.

In a supporting reproductive and developmental toxicity screening study conducted according to OECD Guideline 421 (Inveresk Research, 2003a), male and female Sprague Dawley rats were exposed to 0, 1000, 3000 or 10,000 ppm Gum Rosin (Rosin) in the diet during pre-mating, mating, gestation and lactation for a total of 30 exposure days for males and 41-45 exposure days for females. At 10,000 ppm in the diet (equivalent to 786 mg/kg bw/d for males and 869 mg/kg bw/d for females), there were no test material-related effects on mating performance, male and female fertility indices, or length of gestation and no gross or microscopic effects on reproductive organs of either sex. The mean number of implant sites per pregnancy at this dose level was slightly reduced resulting in a slight reduction in litter size. Mean litter and pup weights were also slightly reduced. The effect on implantation, litter size and fetal weight may be secondary to the effects on decreased food intake and subsequent lower weight gain observed in the adult females. A NOAEL of 3000 ppm, equivalent to 248 (males) to 309 (females) mg/kg bw/d was derived from this study.

A number of repeat dose oral toxicity studies are available on related materials (rosin oligomers, hydrogenated rosin and rosin). Although these studies show no evidence of effects on reproductive organs, the conduct and reporting was of uncertain quality (Klimisch 4) and hence are only included here for completeness, Further repeat dose toxicity studies planned on rosin derivatives, including a 90 -day oral study in rats, will provide additional information relevant to the evaluation of effects on reproductive organs for Distilled tall oil, magnesium salt.

Short description of key information:
One key guideline (OECD 422) combined reproductive/repeat dose toxicity study was conducted with fatty acids C18-(unsaturated) lithium salts. No effects were observed on reproductive performance or foetal developmental in this study at the highest dose tested (1089.75 mg/kg bw/day). In a supporting oral screening study possible effects (reduced number of implantation sites and reduced mean litter and pup weights) were noted at 10000 ppm ( equivalent to approximately 800 mg/kg/day).

Justification for selection of Effect on fertility via oral route:
read-across oral screening study

Justification for selection of Effect on fertility via dermal route:
read-across dermal screening study

Effects on developmental toxicity

Description of key information

One key guideline (OECD 422) combined developmental/repeat dose toxicity study was conducted with fatty acids C18-(unsaturated) lithium salts.  No developmental effects were observed in this study at the highest dose tested (1089.75 mg/kg bw/day). 
In a supporting oral screening study, possible effects (reduced number of implantation sites and reduced mean litter and pup weights) were noted at 10000 ppm ( equivalent to approximately 800 mg/kg/day).

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

288 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 089.75 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

In an OECD 422 combined developmental and repeat dose toxicity ‘screening’ study (Thorsrud, B., 2011), dermal application of Fatty acids C18-(unsaturated) lithium salts to the dorsal surface of Parental male and female rats at dose levels of 100, 300, and 1000 mg/kg/day did not result in any adverse reproductive effects or any definitive test article-related changes in the development or survival of the offspring.

In addition, results from the clinical pathology evaluations and neurobehavioral testing did not reveal any effects that could be attributed to treatment at the dose levels tested. Test article-related dermal changes were limited to local effects at the test site for Parental animals at 300 and 1000 mg/kg/day, which showed a decreasing trend following cessation of dosing in the designated recovery animals. Microscopic evaluation of the skin at the test site showed minimal to moderate erosion/ulceration, epidermal hyperplasia and exudate, minimal to mild acute to subacute/chronic inflammation and minimal edema, which confirmed the macroscopic findings. At recovery necropsy, test article-related microscopic findings in treated skin of animals at 1000 mg/kg/day were morphologically similar, although they occurred at a lower incidence and severity indicating partial resolution of these findings following the recovery period. Microscopic findings of splenic extramedullary hematopoiesis and thymic lymphoid depletion noted at 1000 mg/kg/day were considered to be secondary adaptive responses to parturition and/or localized dermal effects.

Systemic effects were limited to changes in body weight and organ weight at 1000 mg/kg/day, the highest dose level tested.

In summary, there were no treatment related effects at any dose level on the development of the progeny or on any of the developmental parameters evaluated. Based on these data, the NOAEL for developmental toxicity was >1089.75 mg/kg bw/day.

The potential for Gum Rosin (Rosin) to cause developmental toxicity has been evaluated in a supporting' reproductive and developmental toxicity screening study conducted according to OECD Guideline 421 in which male and female Sprague Dawley rats were exposed to up to 10000 ppm test substance in the diet during premating, mating, gestation and lactation for a total of 30 exposure days for males and 41-45 exposure days for females study (Inveresk Research, 2003a). At 10000 ppm in the diet, there was a decrease in weight gain or weight loss over the first few weeks of treatment. Decreased weight gain was more severe in females, occurring during the first week on study. After this period, mean weight gain was similar to controls. Pregnant female weight gain was slightly decreased during the first half of gestation. Food consumption was significantly reduced in the 10000 ppm animals for the first 2 weeks of treatment, for both sexes. Food consumption was also slightly reduced throughout gestation and lactation. Consumption at the two lower levels was similar to that of controls. At 10000 ppm, test substance intake in the first week of treatment was lower than the second week for both sexes. There was also a decreased intake in the first week of gestation at this dietary level. For dams, no test material-related effects were noted on mean gestation length or the process of parturition at any exposure concentration. The number of implantation sites and mean litter and pup weights were slightly reduced for the 10000 ppm dams. There were no obvious external malformations noted in the pups at any of the dose levels in this study. The NOAEL for developmental toxicity was 3000 ppm, equivalent to a received dose of 288 mg/kg bw/d from GD0 to PND4. 

Justification for selection of Effect on developmental toxicity: via oral route:
read-across oral screenig study

Justification for selection of Effect on developmental toxicity: via dermal route:
read-across dermal screening study

Justification for classification or non-classification

The available data do not meet the criteria for classification 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).