Fumes, silica

Endpoint summary

Description of key information

Animal data on the acute toxicity of synthetic amorphous silica, which have been used for read-across, do not show acute oral, inhalation or dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

other: OECD evaluation of an in vivo skin irritation study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A scientific review by authorative international body

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

OECD evaluated the available test data on synthetic amorphous silica.

GLP compliance:

no

Remarks:

review: both yes and no status

Test type:

other: different acute oral toxicity tests

Species:

other: rat and mouse

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 110 mg/kg bw

Remarks on result:

other: hydrophilic precipitated silica

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: hydrophilic precipitated silica

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Remarks on result:

other: several silica types

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 20 000 mg/kg bw

Remarks on result:

other: hydrophilic precipitated silica

Sex:

male

Dose descriptor:

LD50

Effect level:

> 3 160 mg/kg bw

Remarks on result:

other: hydrophilic pyrogenic silica

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

OECD (2004) includes 12 acute oral toxicity studies with synthetic amorphous silica, of which five is regarded as critical study for SIDS endpoint. These five studies are conducted with hydrophilic precipitated or pyrogenic silica. In the critical studies, the LD50 or LDO value was at least >3160 mg/kg bw, thus showing no acute oral toxicity.

Executive summary:

In OECD (2004), the acute oral administration of hydrophilic precipitated or pyrogenic silica either by gavage or in the diet

failed to produce signs of toxicity or deaths in treated animals with LD₅₀ values greater than the top doses applied. Thus, the LD₅₀ values varied from >3100 to >20000 mg/kg bw. In conclusion, acute oral ingestion to high doses of synthetic amorphous silica will produce no systemic toxicity.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 Aug. - 04 Sep. 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann Versuchstierzucht, Borchen/Germany
- Age at study initiation: 9 wks (male), 10 wks (females)
- Weight at study initiation: 183 - 191 g (male), 141 - 152 g (female)
- Fasting period before study: 16 h before start
- Housing: single in Macrolon cages
- Water: ad libitum
- Acclimation period: >= 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 22.5 °C
- Humidity (%): 40 - 70 %
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 / 12 hours

Route of administration:

oral: gavage

Vehicle:

other: aqueous suspension with 1 % carboxymethyl cellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 237 mg silica/mL suspension
- Amount of vehicle (if gavage): 21.5 ml/kg bw (including 5100 mg TS)
- Justification for choice of vehicle: suspending the test material and stabilising the suspension
- Lot/batch no. (if required):

MAXIMUM DOSE VOLUME APPLIED: 21.5 ml/kg bw

Doses:

5110 mg/kg bw
237 mg/ml

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: days 0, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

not relevant

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

none

Clinical signs:

other: no particular findings

Gross pathology:

no particular findings

Interpretation of results:

other: non-toxic

Executive summary:

Jahn et al (1990) studied the acute oral toxicity of precipitated silica in rats. Five male and 5 female animals were used. The dose was applied by gavage as aqueous suspension (21.5 ml/kg bw = 237 mg silica/ml suspension). No acute effects were observed, and the LD₅₀ value was >5,000 mg/kg.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

No toxicological data were available for silica fume and, therefore, a read-across approach was used. The dissolution, composition and surface properties were the most important parameters considered when deciding which substances can be used for read-across.

Based on the composition, surface characteristics, and bioaccessibility data, silica fume was assumed to have toxicological properties similar to those of sparingly synthetic amorphous silicas. Therefore read-across was carried out using available toxicological studies with synthetic amorphous silica (SAS).

Details on the read-across approach are presented in Iuclid section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Interpretation of results:

GHS criteria not met

Conclusions:

Acute toxicity studies on synthetic amorphous silica suggest low toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

other: A scientific review by an authorative international body

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

OECD evaluated the available test data on synthetic amorphous silica.

GLP compliance:

no

Remarks:

'yes' status in critical studies

Test type:

other: different acute inhalation toxicity tests

Species:

rat

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 0.139 mg/L air

Exp. duration:

4 h

Remarks on result:

other: hydrophilic pyrogenic silica

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 0.691 mg/L air

Exp. duration:

4 h

Remarks on result:

other: hydrophilic precipitated silica

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.08 mg/L air

Exp. duration:

4 h

Remarks on result:

other: hydrophilic pyrogenic silica

All acute inhalation studies performed with dry dust were hampered by the technical problem to achieve the recommended highest test concentration of 5 mg/l, apparently attributable to the high adhesive forces which caused rapid precipitation onto equipment walls. Therefore, the maximum attainable chamber concentrations were distinctly lower than envisaged.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

OECD (2004) includes seven acute inhalation toxicity studies with synthetic amorphous silica, of which three are regarded as critical studies for SIDS endpoint. These three studies are conducted with hydrophilic pyrogenic or precipitated silica. In a study where LC50 >2.08 mg/L was suggested, none of the animals died. The SAS dusts are considered as acutely non-toxic.

Executive summary:

The OECD (2004) reviewed that there was no lethal effects following inhalation exposure of rats to the highest technically feasible concentrations of 140 to 2,000 mg/m³ of hydrophilic precipitated or pyrogenic silica. However, the acute inhalation of synthetic amorphous silica dust may cause discomfort and stress as well as signs of local irritation to the nasal, bronchiolar and ocular mucous membranes. In conclusion, the synthetic amorphous silica dust is considered to be acutely non-toxic via an inhalation route.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

No toxicological data were available for silica fume and, therefore, a read-across approach was used. The dissolution, composition and surface properties were the most important parameters considered when deciding which substances can be used for read-across.

Based on the composition, surface characteristics, and bioaccessibility data, silica fume was assumed to have toxicological properties similar to those of sparingly synthetic amorphous silicas. Therefore read-across was carried out using available toxicological studies with synthetic amorphous silica (SAS).

Details on the read-across approach are presented in Iuclid section 13.

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

LC50

Effect level:

> 2.08 mg/L air

Interpretation of results:

GHS criteria not met

Conclusions:

The OECD (2004) reviewed that there was no lethal effects following inhalation exposure of rats to the highest technically feasible concentrations of 140 to 2,000 mg/m3 of hydrophilic precipitated or pyrogenic silica.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

no guideline available

Principles of method if other than guideline:

Four animals per group used, two each treated on the intact and abraded skin: The substance was mixed with distilled water to form an aqueous paste

GLP compliance:

no

Test type:

standard acute method

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

Four animals per group used, two each treated on the intact and abraded skin: The substance was mixed with distilled water to form an aqueous paste

Duration of exposure:

24 h

Doses:

2000, 3000, 4000, and 5000 mg/kg

No. of animals per sex per dose:

4 per dose group

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Local effect: very slight erythema (score 1 of 4), reversible after 2 days (ZEO 49), after 4 d (ZEOSYL) or 5 d (ZEOFREE) in one or a few animals. No systemic signs of toxicity or organ toxicity.
 

Interpretation of results:

GHS criteria not met

Executive summary:

In 1978, Woltjen and Calkins presented their study results on the acute dermal toxicity of precipitated synthetic silicas in four different reports. After acute dermal application of up to 5,000 mg/kg bw of aqueous pastes of precipitated synthetic amorphous silica to the intact and abraded skin of rabbits for 24 hours under occlusive conditions, no signs of systemic or organ toxicity were noted. There were only very slight transient erythemas at the site of treatment in solitary animals. In conclusion, the dermal exposure to high doses of synthetic amorphous silica will produce no systemic toxicity and the LD₅₀ is >5,000 mg/kg.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

No toxicological data were available for silica fume and, therefore, a read-across approach was used. The dissolution, composition and surface properties were the most important parameters considered when deciding which substances can be used for read-across.

Based on the composition, surface characteristics, and bioaccessibility data, silica fume was assumed to have toxicological properties similar to those of sparingly synthetic amorphous silicas. Therefore read-across was carried out using available toxicological studies with synthetic amorphous silica (SAS).

Details on the read-across approach are presented in Iuclid section 13.

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Interpretation of results:

GHS criteria not met

Conclusions:

After acute dermal application of up to 5,000 mg/kg bw of aqueous pastes of precipitated synthetic amorphous silica to the intact and abraded skin of rabbits for 24 hours under occlusive conditions, no signs of systemic or organ toxicity were noted. Conclusion: No classification for acute toxicity via dermal exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

There is data available on the acute toxicity of synthetic amorphous silica. According to this data, the acuteoraltoxicity of synthetic amorphous silica is very low: no signs of toxicity were observed at doses of up to 5,000 mg SiO₂/kg bw. The LD₅₀values for the various types of synthetic amorphous silica studied were quite similar. Also, the dermal toxicity of synthetic amorphous silica is low. Available in vitro dissolution data on synthetic biological fluids shows that the bioaccessibility of silicon ion from silica fume is similar or slightly lower than from synthetic amorphous silica. Thus, the bioavailability of silica fume is expected to be similar or lower than that of synthetic amorphous silica. Based on the read-across from synthetic amorphous silica, silica fume is not acutely toxic orally or dermally.

Animal studies with synthetic amorphous silica do not show any acute inhalation toxicity up to the highest technically achievable doses. Available in vitro dissolution data in synthetic biological fluids and comparative toxicokinetic data suggest that the lung kinetics of silica fume is likely to be similar or slightly slower than that of synthetic amorphous silica. Thus, the read-across from synthetic amorphous silica is justified and no acute inhalation toxicity is expected with silica fume.

The dissolution of impurities from silica fume is generally low and in most cases comparable to that from synthetic amorphous silica. Therefore, they are not likely to hamper the read across from synthetic amorphous silica in the case of acute toxicity.

Justification for classification or non-classification

Based on the read-across from synthetic amorphous silicas, silica fume is not acutely toxic via the oral, inhalation or dermal route.