High temperature calcination products of titanium dioxide, calcium carbonate, calcium fluoride, quartz and antimony oxide containing lewisite and wollastonite

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a short-term toxicity study by the oral route does not need to be conducted because an appropriate inhalation study is available and inhalation is the most appropriate route of administration as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 24 - Sept 10, 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented (GLP, but no real control))

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

no guideline available

Principles of method if other than guideline:

Study of the bioavailability of metal ions from the substance after inhalation as a dust aerosol in rats

GLP compliance:

yes

Remarks:

Deviations: The analysis of Ni and Sb content in the organs of the test animals was performed in a laboratory without quality assurance unit. Therefore, the report was not audited by QAU; the stability of the test substance has not been proven by recharac

Limit test:

yes

Species:

rat

Strain:

other: Wistar/Chbb:THOM

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Age at study initiation: 7 weeks
- Weight at study initiation: 230 - 232 g ( the average weight of the addtional set of animals 304 g ± 1.7 g)
- Housing: Singly in Makrolon/wire cages (type MD III of Becker, Castrop-Rauxel, Germany)
- Diet: KLIBA rat/mouse/hamster laboratory diet 24-343-4 10 mm pellets; Klingentalmühle AG, Kaiseraugst, Switzerland
- Water: during exposure withdrawn


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Remarks on MMAD:

MMAD / GSD: 0.6 - 1.0 µm/ 2.8 - 4.1 (measurements on d 3 and d 5

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: aerodynamic exposure apparatus (INA 60, volume V 90 l, BASF Aktiengesellschaft)
- Method of fixing animals in test chamber: exposure tubes; animal snouts projecting into the inhalation chamber
- Rate of air: Supply air (l/h): compressed air 1,500, blast air 4,500; Exhause air (l/h): 5,400
- System of generating particulates/aerosols: dust generator
- Temperature, humidity: 23.3-23.6 °C , 50.6-54.0 %
- Method of particle size determination: Gravimetrical determination

TEST ATMOSPHERE
- Samples taken from breathing zone: yes

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

5 days

Frequency of treatment:

6 hours/day, daily

Remarks:

Doses / Concentrations:
60 mg/m3 (0.06 mg/l)
Basis:
nominal conc.

No. of animals per sex per dose:

50 (divided into 5 groups with differing post-exposure periods)

Control animals:

other: During analyses of livers and kidneys of the first test groups the need occurred to analyse kidneys of untreated animals (blank values), therefore another set of animals was delivered age-matched to the test animals of test group 1 at sacrifice.

Details on study design:

Post-exposure period: 0, 3, 10, 31, 60 days

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at least 3 times on exposure days and, as a rule, once during the preflow period and the post-exposure observation period.
BODY WEIGHT: Yes
- Time schedule for examinations: at the beginning of preflow, at the beginning of exposure period and then once a week

Sacrifice and pathology:

Control group was sacrificed on day of arrival
Group 1 on test day four (after the last exposure)
Group 2 at day 7 (post-exposure day 3)
Group 3 at day 14 (post-exposure day 10)
Group 4 at day 35 (post-exposure day 31)
Group 5 at day 64 (post-exposure day 60)

Other examinations:

ANALYSIS: Ni and Sb concentrations in lung, liver and kidneys were determined by ICP-MS; Food analysis: contaminations in the used commercial feed were 1.42 mg Ni/kg and 13 µg Sb/kg.

Statistics:

no statistical evaluation because no concurrent control.

Details on results:

No effects on mortality, clinical signs, body weights and body weight gains

Dose descriptor:

NOAEC

Effect level:

60 mg/L air

Remarks on result:

not determinable

Remarks:

no NOAEC identified

Critical effects observed:

not specified

CONTENT OF Ni AND Sb in:
LIVER: 
Mean Sb concentration (quantification limit 0.2 ng/g) in unexposed animals was 1.1 ng/g; directly post-exposure
and on day 3-post-exposure the concentration was about 4-fold higher in exposed animals, during further observation
the concentration was similar to unexposed animals (1.3 ng/g on day 10).
Mean Ni-concentration was in the same range in exposed and unexposed animals (however, below the quantification limit
of 10 ng/g; outliers not considered). 

KIDNEYS: 
Mean Sb concentration in unexposed animals was below the detection limit (1 ng/g), in exposed animals it was above the 
detection limit but below the quantification limit (3 ng/g), only the day 3 post exposure group reached a value of 5.6 
ng/g (2-3-fold increase compared with other observation days).
Mean Ni concentration was below the detection limit (1 ng/g) in unexposed animals and above detection limit but below
quantification limit (25 ng/g) in exposed animals, except on day 3 post-exposure 94 ng/g were determined (10-fold more
than in other exposure groups. Authors comment: presumably due to contamination of the sample). 

LUNG: 
Directly post-exposure the mean Ni and Sb concentration was 79 and 202 µg/lung , respectively (corresponding to 2 mg of
pigment/lung). The concentration declined during the post-exposure period, following first order kinetics; the clearance 
half-life was 50 days.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

subacute

Species:

rat

Quality of whole database:

This study was primarily a bioavailability study in which five groups of 10 male rats were dosed for 6 hours/day for five consecutive days via nose-only inhalation exposure at a single dose level of 60 mg/m3 (0.06 mg/L). The principal objective was to sacrifice the groups of ten animals on days 0, 3, 10, 31 and 60 following completion of the exposure period and analyse liver, kideneys and lungs from ach animal for Ni and Sb concentrations.
Basic toxicological endpoints such as body weight and clinical examinations were also conducted.

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 24 - Sept 10, 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented (GLP, but no real control))

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

no guideline available

Principles of method if other than guideline:

Study of the bioavailability of metal ions from the substance after inhalation as a dust aerosol in rats

GLP compliance:

yes

Remarks:

Deviations: The analysis of Ni and Sb content in the organs of the test animals was performed in a laboratory without quality assurance unit. Therefore, the report was not audited by QAU; the stability of the test substance has not been proven by recharac

Limit test:

yes

Species:

rat

Strain:

other: Wistar/Chbb:THOM

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Age at study initiation: 7 weeks
- Weight at study initiation: 230 - 232 g ( the average weight of the addtional set of animals 304 g ± 1.7 g)
- Housing: Singly in Makrolon/wire cages (type MD III of Becker, Castrop-Rauxel, Germany)
- Diet: KLIBA rat/mouse/hamster laboratory diet 24-343-4 10 mm pellets; Klingentalmühle AG, Kaiseraugst, Switzerland
- Water: during exposure withdrawn


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Remarks on MMAD:

MMAD / GSD: 0.6 - 1.0 µm/ 2.8 - 4.1 (measurements on d 3 and d 5

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: aerodynamic exposure apparatus (INA 60, volume V 90 l, BASF Aktiengesellschaft)
- Method of fixing animals in test chamber: exposure tubes; animal snouts projecting into the inhalation chamber
- Rate of air: Supply air (l/h): compressed air 1,500, blast air 4,500; Exhause air (l/h): 5,400
- System of generating particulates/aerosols: dust generator
- Temperature, humidity: 23.3-23.6 °C , 50.6-54.0 %
- Method of particle size determination: Gravimetrical determination

TEST ATMOSPHERE
- Samples taken from breathing zone: yes

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

5 days

Frequency of treatment:

6 hours/day, daily

Remarks:

Doses / Concentrations:
60 mg/m3 (0.06 mg/l)
Basis:
nominal conc.

No. of animals per sex per dose:

50 (divided into 5 groups with differing post-exposure periods)

Control animals:

other: During analyses of livers and kidneys of the first test groups the need occurred to analyse kidneys of untreated animals (blank values), therefore another set of animals was delivered age-matched to the test animals of test group 1 at sacrifice.

Details on study design:

Post-exposure period: 0, 3, 10, 31, 60 days

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at least 3 times on exposure days and, as a rule, once during the preflow period and the post-exposure observation period.
BODY WEIGHT: Yes
- Time schedule for examinations: at the beginning of preflow, at the beginning of exposure period and then once a week

Sacrifice and pathology:

Control group was sacrificed on day of arrival
Group 1 on test day four (after the last exposure)
Group 2 at day 7 (post-exposure day 3)
Group 3 at day 14 (post-exposure day 10)
Group 4 at day 35 (post-exposure day 31)
Group 5 at day 64 (post-exposure day 60)

Other examinations:

ANALYSIS: Ni and Sb concentrations in lung, liver and kidneys were determined by ICP-MS; Food analysis: contaminations in the used commercial feed were 1.42 mg Ni/kg and 13 µg Sb/kg.

Statistics:

no statistical evaluation because no concurrent control.

Details on results:

No effects on mortality, clinical signs, body weights and body weight gains

Dose descriptor:

NOAEC

Effect level:

60 mg/L air

Remarks on result:

not determinable

Remarks:

no NOAEC identified

Critical effects observed:

not specified

CONTENT OF Ni AND Sb in:
LIVER: 
Mean Sb concentration (quantification limit 0.2 ng/g) in unexposed animals was 1.1 ng/g; directly post-exposure
and on day 3-post-exposure the concentration was about 4-fold higher in exposed animals, during further observation
the concentration was similar to unexposed animals (1.3 ng/g on day 10).
Mean Ni-concentration was in the same range in exposed and unexposed animals (however, below the quantification limit
of 10 ng/g; outliers not considered). 

KIDNEYS: 
Mean Sb concentration in unexposed animals was below the detection limit (1 ng/g), in exposed animals it was above the 
detection limit but below the quantification limit (3 ng/g), only the day 3 post exposure group reached a value of 5.6 
ng/g (2-3-fold increase compared with other observation days).
Mean Ni concentration was below the detection limit (1 ng/g) in unexposed animals and above detection limit but below
quantification limit (25 ng/g) in exposed animals, except on day 3 post-exposure 94 ng/g were determined (10-fold more
than in other exposure groups. Authors comment: presumably due to contamination of the sample). 

LUNG: 
Directly post-exposure the mean Ni and Sb concentration was 79 and 202 µg/lung , respectively (corresponding to 2 mg of
pigment/lung). The concentration declined during the post-exposure period, following first order kinetics; the clearance 
half-life was 50 days.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no study available