Silicon dioxide

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1958

Report date:

1958

Reference 2

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

2 dose l, 18 hrs/d, 5 d/wk
21-Day dermal exposure study

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Silicon dioxide

EC Number:

231-545-4

EC Name:

Silicon dioxide

Cas Number:

7631-86-9

Molecular formula:

O2Si

IUPAC Name:

dioxosilane

Test material form:

solid: nanoform, no surface treatment

Details on test material:

CAS 112945-52-5, Pyrogenic, Surface area / BET [m2/g] 175-225

Specific details on test material used for the study:

Cab-O-Sil

Test animals

Species:

rabbit

Strain:

not specified

Remarks:

albino

Details on species / strain selection:

1.5 - 1.9 kg

Sex:

male/female

Details on test animals or test system and environmental conditions:

Throughout the study the animals were housed individually in metal cages elevated above the droppings. Food, consisting of Purina Rabbit Pellets and water, was available at all times.

Administration / exposure

Type of coverage:

not specified

Vehicle:

methylcellulose

Details on exposure:

on intact and abraded skin (2 animals each per dose group) in 0.5 % methyl cellulose

Duration of treatment / exposure:

3 wks

Frequency of treatment:

18 h/d, 5 d/wk

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

5 000 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

10 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

2

Control animals:

yes, concurrent vehicle

other: positive control: cosmetic talc

Positive control:

#1625 Cosmetic talc (10 g/kg bw/d)

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

effects observed, non-treatment-related

Description (incidence and severity):

In general the animals of each control and test group exhibited mild erythema and mild to moderate atonia consistently throughout the experimental period. From the beginning of the second week until tne time of sacrifice the exposed skin of each animal showed mild or moderate desquamation. Among the control and test rabbits with abraded skin areas, there appeared to be complete healing of the skin during each week foilowing the periodic abrasions. The skin immediately surrounding the abrasions showed a slightly greater degree of erythema than the remaining exposed skin. Otherwise, the degree of irritation was comparable among the intact and abraded skin animals of each group.

Mortality:

mortality observed, non-treatment-related

Description (incidence):

one death in control group

Body weight and weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

The majority of the animals in test groups receiving CAB-O-SIL gained weignt at a normal rate throughout the experimental period. The initial weight loss among several animals in the control groups was attributed to the initial challenge from infection; however during the latter part of the study these animals showed gains in body weight.

Clinical biochemistry findings:

effects observed, non-treatment-related

Description (incidence and severity):

Examination of the analytical data shows that there was no significant difference in the silicon dioxide content of urine, blood, kidney, liver or spleen between the control and test animals.

Urinalysis findings:

effects observed, non-treatment-related

Description (incidence and severity):

Examination of the analytical data shows that there was no significant difference in the silicon dioxide content of urine, blood, kidney, liver or spleen between the control and test animals.

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, non-treatment-related

Description (incidence and severity):

At gross autopsy performed following sacrifice the livers of the majority of the animals contained parasitic areas which resembled coccidiosis. In addition the mesentery of one animal contained parasitic cysts resembling larval tapeworm cysts.Otherwise the organs of each animal appeared grossly within normal limits.

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

effects observed in control and treated groups

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

>= 10 000 mg/kg bw/day (nominal)

Sex:

male/female

Target system / organ toxicity

Key result

Critical effects observed:

no

Any other information on results incl. tables

During the first two weeks several animals, particularly from the negative and positive control groups, exhibited diarrhoea and weight loss. From experience in this laboratory these findings suggested an intestinal infection, probably coccidiosis, and the involved animals were given one to three daily intramuscular injections of Streptomycin. Most of the animals responded to the antibiotic therapy with subsequent weight gains and disappearance of the diarrhoea. The single death that occurred in the negative control group on the 13th day was attributed to the challenge from infection. Except for the challenge from infection, the appearance and behaviour of each control and experimental animal were essentially normal.

Applicant's summary and conclusion

Conclusions:

Under the test conditions employed there was no evidence of systemic toxicity or of gross or microscopic pathology which could be associated witn application of CAB-O-SIL. The silicon dioxide content of blood, urine, spleen, liver, and kidney was comparable for control arid test animals.
Each control material and CAB-O-SIL produced a mild dermal irritation consisting of erythema, atonia, and desquamation. There appeared to be no significant difference in dermal irritative potential between the methyl cellulose solution, #1625 Cosmetic.Talc and CAB-O-SIL.

Executive summary:

The 21d dermal toxicity potential of Cab-O-SIL was examined in rabbits.