Bentonite, acid-leached

Endpoint summary

Additional information

Justification for read across

No repeat dose studies are available for bentonite acid leached. However there are supporting repeat dose studies in the literature with both bentonite and calcium montmorillonite.

Both bentonite and bentonite acid leached consist primarily of smectite minerals, mainly montmorillonite. The mineralogy of bentonite acid leached can be considered as: Smectite (montmorillonite), amorphous silica, feldspar, sepiolite, kaolinite, quartz and the minerology of bentonite can be considered as: Smectite (montmorillonite), calcite, opal, dolomite, feldspar, kaolinite, quartz. Bentonite acid leached is originated from bentonite. To form bentonite acid leached bentonite is digested with water and mineral acid in a vessel. The acid-leached treatment results in opening the mineralogical structure and in removing some impurities (e.g. trapped accessory minerals). It is not expected that this process significantly effects the toxicological properties of bentonite acid leached in comparison to bentonite and therefore read across between the two substances is considered valid.

Repeat dose oral studies:

Bentonite acid leached is mostly used in industrial/professional settings where good industrial hygiene is employed and thus oral ingestion is not expected. Bentonite acid leached is not acutely toxic by the oral route and has relatively low bioavailability. There are several studies available in the literature which provide supporting data demonstrating that analogous substances when ingested orally do not present any toxicological effects.

 

A supporting developmental toxicity study from the literature is available with bentonite from which bentonite acid leached is derived (Abdel-Waheb 1999 summarized insection 7.8.1). In the study bentonite was administered to rats at a dose of ~250 mg/kg/day. No toxic effects were observed either maternally or developmentally. More recently a study in which rats ingested NovaSil clay (a naturally occurring calcium montmorillonite clay) at dietary doses as high as 2% throughout pregnancy showed neither maternal nor fetal toxicity (Wiles 2004 summarized insection 7.5.1).

 

In a further supporting study in the literature (Afriyie-Gyawu 2005 summarized insection 7.5.1) a subchronic toxicity study in rats was performed with NS clay ingested at dietary doses of 2% for 28 weeks. No treatment related effects were observed. This study led to a clinical trial study in humans (Afriyie-Gyawu 2008 summarized insection 7.10.3) whereby volunteers were administered NS clay at the highest dose of 3.0 g NS clay per day for 3 months which demonstrated that NS clay is a safe and practical for the protection of humans against aflatoxins in populations at high risk of aflatoxicosis.    

Based on the available data of the analogous substances it was considered scientifically unjustified to perform a repeat dose oral study with bentonite acid leached

Repeat dose inhalation studies:

No repeat dose inhalation studies have been performed.

 

An intratracheal study has been performed with the read across substance bentonite (Creutzenberg 2008). The Creutzenberg study is not a complete repeated dose inhalation study as administration of bentonite was performed by intratracheal instillation for 4 consecutive days followed by a 90 day observation period. The study is unfortunately also not suitable for a quantitative assessment as the route of administration was intratracheal. However, the study clearly demonstrates that there are significant differences in toxicity following administration of equivalent doses of quartz as either bentonite (15.2 mg of bentonite with 60% quartz) or reference quartz (10.5 mg of 87% quartz). The reference-quartz caused significant, self-perpetuating lung toxicity while bentonite demonstrated significantly less toxicity and partial recovery during the study period. The main effect of bentonite was slight fibrosis and inflammation of the lung. The relevance of these findings to humans is complicated by the exposure route (intra-tracheal) and the appropriateness of using rat as a model for inhalation toxicity studies of poorly soluble particles.

 

Rats are believed to be particularly sensitive to the effects of inhalation of poorly soluble particles due to reduced lung clearance rates relative to many other species (Elderet al2005,Oberdörsteret al1995). This is believed to be due to both airway geometry and reduced macrophage capacity in the rat. The resulting effect is lung overload and with corresponding typical observations of inflammation and fibrosis. In chronic studies, increased tumor incidences are also observed in rats relative to other species. These effects are not specific to the substance but merely represent overload of poorly soluble particles. Thus, the effects seen in rats at very high concentrations (such as the Creutzenberg study) may not be relevant for humans as the human equivalent dose will not be reached under relevant exposure conditions. If the effects seen in rats are truly species-specific, these results will be unreliable for the human risk assessment and for classification purposes. There is an ongoing scientific debate regarding how to interpret data, and the relevance to human exposure, from rat inhalation studies of poorly soluble particles (ILSI Risk Science Institute Workshop 2000). There is currently support that neoplastic changes seen in rat studies performed under lung overload conditions are not relevant for humans, however no consensus has been reached regarding non-neoplastic changes. Nevertheless, there are comparative studies demonstrating that rat lung is significantly more sensitive to inflammation than monkey lung (Nikula 1997) and mouse and hamster lung (Elder 2005). Accordingly, it is likely that the lung overload effect not only impacts neoplastic changes but also general lung toxicity. 

Although bentonite acid-leached contains significant amounts of quartz, the reliable study on bentonite by Creutzenberg demonstrates that a simple bridging of toxicity data from quartz to bentonite acid-leached is not appropriate.

 

References:

ILSI Risk Science Institute Workshop Participants (2000) The Relevance of the Rat Lung Response to Particle Overload for Human Risk Assessment: A Workshop Consensus Report. Inhal Toxicol 12:1-17

 

Nikula KJ, Avila KJ, Griffith WC, Mauderly JL (1997) Lung Tissue Responses and Sites of Particle retention Differ between Rats and Cynomolgus Monkeys Exposed Chronically To Diesel Exhaust and Coal Dust.Fund Appl Toxicol 37:37-57

 

Elder A, Gelein R, Finkelstein JN, Driscoll KE, Harkema J, Oberdörster G (2005) Effects of Subchronically Inhaled Carbon Black in Three Species. I. Retention kinetics, Lung Inflammation, and Histopathology. Toxicol Sci 88(2):614-629

 

Oberdörster G (1995b) Lung particle overload: Implications for occupational exposures to particles. Reg. Tox. Pharmacol. 27: 127-135

Repeat dose dermal:

No repeat dose dermal studies have been performed as this is not considered to be a significant route of exposure based on the low potential of dermal penetration.

Justification for classification or non-classification

No classification is considered applicable for specific target organ toxicity upon repeated exposure (STOT-RE). There is no concern for the dermal or oral route. The inhalation route is considered to be the primary route of exposure. 

Although bentonite acid leached contains respirable crystalline silica it is not considered appropriate for a classification of STOT-RE to be applied to this substance as studies have demonstrated that a simple bridging of toxicity from quartz to bentonite acid leached is not appropriate.