Kaolin, calcined

Endpoint summary

Description of key information

Oral: 
NOAEL (male rats): 1760 - 3000 mg/kg bw/day (RA Syloid 244; 103 weeks)
NOAEL (female rats): 1780 - 3210 mg/kg bw/day (RA Syloid 244; 103 weeks)
Dermal:
No dermal repeated dose toxicity studies.
Inhalation: 
NOAEC (rats): 1.3 mg/m³  (RA Aerosil 200; 13 weeks)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

1 760 mg/kg bw/day

Study duration:

chronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

1.3 mg/m³

Study duration:

subchronic

Species:

rat

Additional information

Oral

There are no data available for Kaolin, calcined. However, some investigations on repeated dose toxicity by the oral route are available for silica gel, cryst.-free (Syloid 244). Similar to OECD 453 a combined chronic toxicity/carcinogenicity study was carried out (Takizawa et al. 1988, RL2). No particular adverse effects were observed in rats and mice treated with Syloid 244 lifelong at dietary level of 5%, corresponding to 1760 - 3000 mg/kg bw/day and 1780 - 3210 mg/kg bw/day for male and female rats, respectively and 5270 – 7490 mg/kg bw/day and 3950 – 13310 mg/kg bw/day for male and female mice, respectively .

In a feeding study, conducted similar to OECD 408, male and female rats received Syloid 244 for 26 weeks (Hackenberg 1975, RL2). No treatment-related findings were noted up to and including 8980 mg/kg bw/day. 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.

 

Dermal

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

Inhalation

There are no data available for Kaolin, calcined. However, some investigations on repeated dose toxicity by inhalation are available for structure-analogue substances. 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/m³ induced 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/m³ rats, and to a lesser degree, in the 5.9 mg/m³ group. 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, RL2).

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, RL2; Arts and Kuper, 2003, RL2). 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.

The inhalation of respirable particles of synthetic amorphous silica (SAS) produces a time- and dose-related inflammation response of the lung tissue in animal studies. Progressive events following excess exposure are characterised as “interstitial fibrosis/early nodular fibrosis/incipient fibrosis”. However, a progression process of any lesion has not been observed like that seen after quartz exposure, i.e. all observations suggest reversibility. There are no signs of classical nodular silicosis or a lymphatic-type pneumoconiosis. On the other hand, crystalline silica produces persistent lung inflammation even at much lower exposure levels (Johnston et al., 2000, RL2).

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., 1980, RL4). 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:

Based on data for structural analogue substances, no repeated dose oral toxicity is expected from the exposure to Kaolin, calcined. There is no need for classification according to DSD (67/548/EEC) or CLP (1272/2008/EC).

 

Dermal:

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

 

Inhalation:

Based on data for structural analogue substances there is no need for classification of Kaolin, calcined according to DSD (67/548/EEC) or CLP (1272/2008/EC).