Silicic acid, aluminum magnesium salt

Endpoint summary

Description of key information

Oral: Syloid 244
NOAEL (male): 1760 - 3000 mg/kg bw/day for rats
NOAEL (female): 1780 - 3210 mg/kg bw/day for rats
NOAEL (male): 5270 - 7490 mg/kg bw/day for mice
NOAEL (female): 3950 - 13310 mg/kg bw/day for mice
Dermal
No dermal repeated dose toxicity studies.
Inhalation: Aerosil 200
NOAEC (subchronic, Aerosil 200): 1.3 mg/m

Additional information

Oral

Only secondary literature is available on Silicic acid, aluminium magnesium salt for repeated dose toxicity (oral). The original studies are not available and documentation of the reviewed data is limited. Therefore data of MAS are insufficient for assessment. However, there are data for structurally related compounds.

Similar to OECD 453 a combined chronic toxicity/carcinogenicity study was carried out. No particular adverse effects were observed in rats and mice treated with Syloid 244 lifelong at dietary level of 5%, corresponding to1760 - 3000mg/kg bw/day and1780 - 3210 mg/kg bw/dayfor male and female rats, respectively and5270 – 7490 mg/kg bw/day and 3950 – 13310 mg/kgbw/day for male and female mice, respectively (Takizawa et al. 1988).

In a feeding study, conducted similar to OECD 408, male and female rats received Syloid 244 for 26 weeks. No treatment-related findings were noted up to and including 8980 mg/kg bw/day (Hackenberg 1975). Isolated pathological findings were unrelated to dosing and common in untreated rats. No histopathological changes were observed in the kidneys and reproductive organs. The effect level (NOAEL) was > 8980 and > 7950 mg/kg bw/day for females and males, respectively.

The following reviewed data are available onSilicic acid, aluminium magnesium salt:In short-term toxicity studies (10 days; oral), no adverse effects were found mice or rabbits dosed up to 5000 mg/kg bw or 10,000 mg/kg bw, respectively (Munch 1945). In a 90 day feeding study, rats and dogs were administered 2, 5, 10, 20 % of the test material in the diet (FDRL 1958). One male rat of the 2 % group diet and one of each sex of the 10 % group died. These rats had fibrinous exudates in the thorax, hemorrhagic lungs, and evidence of respiratory infection at necropsy. Silicon content of the spleens was slightly increased in the 5 % and 10 % groups. No gross findings or significant abnormalities were found in microscopic examinations. In dogs, no animals died and no abnormalities were found in hematological examinations. Silicon concentration of the spleens of the test animals were slightly elevated compared to controls.A further subchronic feeding study, administered rats and dogs 10 % of the test material in the diet (CTFA 1999). No toxic changes were noted. Based on the limited documentation of the reviewed studies, the available data of MAS are insufficient for assessment and only data of the structurally related compounds were taken into account for risk assessment.

Dermal

Repeated dose toxicity studies are not available for the dermal route.

Inhalation

No experimental data are available for Silicic acid, aluminium magnesium salt on inhalation repeated dose toxicity. However, there are data for structurally related compounds.

Several repeated dose inhalation studies have been conducted with synthetic amorphous silica, using various animal species, mostly rat, but also guinea pig and monkey. The exposure concentrations ranged between approx. 1 and 31 mg/m³.

A repeated dose inhalation study (13 weeks) including recovery intervals of up to one year, was carried out to investigate the effects of Aerosil 200 (pyrogenic synthetic amorphous silica). Dose-related changes caused by inflammatory reactions of the tissue were observed in the lung of animals exposed to the test material. Associated lesions only partly recovered during the one-year post-exposure period at the top exposure level. The level of 1.3 mg/m³induced only slight changes, which generally disappeared quickly (cellular infiltration, stimulation of collagen production and increase in lung weight). Focal interstitial fibrosis was not noted directly after the exposure period of 3 months, but appeared with a delay in the 31 mg/m³rats, and to a lesser degree, in the 5.9 mg/m³group. Interestingly, all types of pulmonary lesions were more marked in males than in females. Treatment-related, microscopic changes in the nasal region were occasionally found at the end of the exposure period such as focal necrosis and slight atrophy of the olfactory epithelium (Reuzel et al. 1991).

 

In a short-term inhalation study programme, three synthetic amorphous silica (precipitated, pyrogenic, gel silica types) were investigated in comparison to a crystalline silica as positive control (Arts et al. 2003, Arts and Kuper 2003a+b). Wistar rats were exposed to 1, 5 and 25 mg/m³(nominal concentration) of each silica for 5 days, 6 hours/day. Satellite groups were exposed correspondingly and kept for a recovery period of one and three months. The silica gel and the pyrogenic silica were only examined in males because they had proven to be more sensitive than females, as observed in the study of the precipitated silica.

For all tested synthetic amorphous silica a similar effect profile was determined. In general, the high exposure concentrations (25 mg/m³) induced dose-related effects which reflected an inflammatory response of the lung tissue, associated with a slight morphological tissue reaction (hypertrophy, partly hyperplasia of the bronchiolar epithelium). All observed changes disappeared or tended to disappear during the recovery period, showing clear signs of reversibility, while recovery was not observed in the positive control group (crystalline silica). For the precipitated silica (Zeosyl 45) and the silica gel (Syloid 74), effects at the mid-exposure concentration (5 mg/m³) were confined to very slight increases in the relative neutrophil count with a concomitant decrease in the relative macrophage count at the day after exposure. There were no morphological tissue changes. For the pyrogenic type (Cab-O-Sil M5), slight hypertrophy of the bronchiolar epithelium was noted also at the mid-dose level and a slight body weight loss for all tested concentration levels. No effects were noted at the low concentration levels (1 mg/m³) of Zeosyl 45 and Syloid 74.

 

Prolonged exposure of rats (3, 6 and 12 months), guinea pigs and monkeys (10 to 18 months) to 15 mg/m³(total dust) precipitated, pyrogenic and gel silica produced effects including impairment of lung function, clear inflammatory reactions with signs of early nodular fibrosis (Groth et al. 1981). High deposition of synthetic amorphous silica was noted in macrophages in lung and tracheal lymph nodes of the monkeys, not or barely found in rat and guinea pig. Macrophage and mononuclear cell aggregation was found to be significantly more pronounced in monkeys (bronchioles, aleveolar ducts venules, arterioles) than in rats and guinea pigs. However, it has to be emphasised that this study is not assignable (RL4) because of very limited documentation of the rat and guinea pig studies and shortcomings in the monkey test (accidential preexposure to asbestos) but the results are useful in relation to finding of other studies.

Justification for classification or non-classification

Oral

After oral application, no adverse effects could be observed for long-term administration of Syloid 244 to rats and mice. Based on the chemical structure, no acute oral toxicity is expected from the exposure to silicic acid, aluminium magnesium salt. No need for classification.

 

Dermal

Repeated dose toxicity studies are not available for the dermal route.

 

Inhalation

The inhalation of respirable particles of synthetic amorphous silica produced time- and dose-related inflammatory effects in the lungs and the associated lymph nodes of the experimental animals. However, no progressive process of lesions has been observed as seen for cristalline silica. All synthetic amorphous silica induced effects suggested reversibility.

As silicic acid, magnesium aluminium salt usually agglomerates to larger particles (see chapter 1.3), most of the inhaled material will be retained in the upper airways and/or be swallowed. No need for classification.