Overbased reaction products of distilled tall oil and magnesium hydroxide’

Endpoint summary

Additional information

The following information can be drawn on the basis of a review of available experimental data from physicochemical and toxicological studies on Fatty acids C18-(unsaturated) lithium salts performed according to international technical guidelines and in compliance with GLP in internationally recognised contract research organisations:

o   Fatty acids C18-(unsaturated) lithium salts is absorbed via the gastrointestinal tract. This is supported by the observation of signs of systemic toxicity (i.e. hunched posture, pilo-erection, ataxia, noisy respiration, sneezing, increased salivation) at 2000 mg/kg bw, as an aqueous suspension via oral gavage in an acute oral toxicity study in female Wistar rats.

o   Fatty acids C18-(unsaturated) lithium salts is absorbed to some degree via the skin. This is supported by the observation of a dose-related, but not statistically significant, increase in stimulation index following topical application of Fatty acids, C18-(unsaturated) lithium salts in an ethanol/distilled water (7:3) suspension in a local lymph node assay.

o   In addition, in the dermal combined repeat dose toxicity study with a reproduction/developmental toxicity screening study in rats, systemic effects (statistically significant decrease in body weight) were noted at the highest tested dose of 1089.75 mg/kg bw.

No available data allow conclusions to be drawn regarding distribution, metabolism or excretion of fatty acids C18-(unsaturated) lithium salts.

Endpoint specific guidance (ECHA, 2008) indicates that absorption of substances following exposure by inhalation, skin contact or ingestion may be predicted based on log Pow and water solubility. Experimentally determined results for substances in this category are as follows:

Substance	Log Pow	Solubility (mg/L)
Rosin	3.0 - >6.0	0.9
Rosin, hydrogenated	3.4	1.2
Rosin, reaction products with formaldehyde	5.36	8.1
Resin acids and rosin acids, reaction products with formaldehyde, potassium salts	5.37->6.5	<438 mg/l
Rosin, oligomers	>6.5	<2.2
Resin acids and rosin acids, sodium salts	3.0 - 5.8	miscible
Resin acids and rosin acids, potassium salts	3.1 - 5.9	miscible
Resin acids and rosin acids, calcium salts	3.0	42.6
Resin acids and rosin acids, magnesium salts	0.74	65
Resin acids and rosin acids, calcium zinc salts	1.8	18.2

ECHA (2008) indicates that uptake of substances by the lung is favoured by moderate log P values (between -1 and 4) with micellular solubilisation favoured where log P is >4 and water solubility is low (< 1 mg/L). Data summarised above indicate that Rosin, Rosin, hydrogenated and Rosin, oligomers may be absorbed by lung tissue although the extent of uptake is unclear. No conclusion can be reached regarding possible uptake of Rosin, reaction products with formaldehyde. Absorption of the monovalent and divalent salts by the lung depends on pH: if ionised (as at alkaline pH for the monovalent cation), significant absorption is unlikely on the grounds of hydrophilicity while if the pH is lowered the unionised molecule (the acid) is insoluble and should behave similarly to parent substance. A low vapour pressure means that substances in this category are unlikely to exist as vapour, with exposure limited to inhalation of material deposited as particles.

Dermal absorption of highly water soluble substances may occur where the log Pow is between 1-4 with log Pow values between 2 and 3 favouring uptake. When log Pow exceeds 4, penetration may be limited by the rate of transfer between the stratum corneum and epidermis although uptake of a substance by the stratum corneum will be high. Uptake of substances where log Pow exceeds 6 will be low (ECHA, 2008). Data summarised above suggests that the unionised salts may be absorbed to some extent by skin while uptake of the parent substances is not expected.

Considering absorption after ingestion, uptake from the gastrointestinal tract by passive diffusion is favoured for substances with a log Pow between -1and 4. Absorption via micelle formation may occur where log Pow is >4 and water solubility is <1 mg/l (ECHA, 2008).

Physico-chemical data summarised in the table above suggest that Rosin, Rosin, hydrogenated and rosin, oligomers may be absorbed to some extent after ingestion if they form mixed micelles, whereas uptake of the monovalent and divalent salts is less likely as they will be in ionised form.