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Description of key information

Acute Oral Toxicity

The key study was conducted in accordance with GLP and the standardised guidelines OECD Guidelines for Testing of Chemicals (1981) No. 401 "Acute Oral Toxicity" referenced as method B1 in Annex V of EEC Commission Directive 84/449/EEC. The acute oral median lethal dose (LD50) of the test material, Zinc Hydroxystannate, in the Sprague-Dawley CFY strain rat was found to be greater than 5000 mg/kg bodyweight.

 

Acute Inhalation Toxicity 

The key study was conducted in accordance with GLP and the standardised guidelines OECD Guidelines for Testing of Chemicals (1981) No. 403 "Acute Inhalation Toxicity" referenced as method B2 in Annex V of EEC Commission Directive 84/449/EEC. The acute inhalation LC50 of the test material, Zinc Hydroxystannate, in the Sprague-Dawley CFY rat was greater than 4.35 mg/litre. 

 

Acute Dermal Toxicity

 In accordance with Section 8.5.3, Column 2 of REACH Annex VIII it is considered appropriate to omit the acute toxicity testing by the dermal route as the physicochemical and toxicological properties of the substance do not suggest potential for a significant rate of absorption through the skin.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 February 1989 - 8 March 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across to similar substance. Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Justification for type of information:
See read-across justification in Section 13.
Reason / purpose:
other: Target substance
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bantin & Kingman Ltd., Grimston, Aldborough, Hull, U.K
- Age at study initiation: 5 – 8 weeks
- Weight at study initiation: Males 121 – 131g; Females 120 – 145 g
- Fasting period before study: Overnight fast immediately before dosing and for approximately two hours after dosing
- Housing: The animals were housed in groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding.
- Diet (e.g. ad libitum): ad libitum with the exception of fasting period. Free access to food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.)
- Water (e.g. ad libitum): ad libitum with the exception of fasting period. Free access to mains drinking water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23°C
- Humidity (%):50 - 58%. relative
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

IN-LIFE DATES: From: To: 22 February 1989 - 8 March 1989
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material preparation at a dose level of 5000 mg/kg bodyweight.
All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
No. of animals per sex per dose:
5 male and 5 female
Control animals:
no
Details on study design:
Procedure
a) Range-finding Study
In order to establish a suitable dose level for the main study groups of two rats (one male and one female) were treated once only as follows:

Dose Level (mg/kg) Concentration (mg/mL) Dose Volume (mL/kg) Number of Rats
Male Female
5000 500 10 1 1
3000 300 10 1 1
1000 100 10 1 1
250 25 10 1 1

Animals were observed 1 and 4 hours after dosing and then daily for five days.
Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.


b) Main Study
A group of ten rats (five males and five females) was dosed as follows in order to confirm the findings of the range-finding study:


Dose Level (mg/kg) Concentration (mg/mL) Dose Volume (mL/kg) Number of Rats
Male Female
5000 500 10 5 5

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Animals were observed 1 and 4 hours after dosing and subsequently once daily for 14 days. Deaths and evidence of overt toxicity were recorded at each observation.
Individual bodyweights were recorded on the day of treatment (day 0) and on days 7 and 14.
All animals were subjected to gross necropsy examination for any macroscopic abnormalities. No tissues were retained.
Statistics:
Evaluation of Data
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made. Clinical observations, bodyweight and necropsy records were examined for any adverse but nonlethal effects resulting from treatment.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
Mortality Data

Range-finding Study:
No deaths (0/2)

Main Study
No Deaths (0/10)
Body weight:
All animals showed expected gain in bodyweight over the study period
Gross pathology:
No abnormalities were noted at necropsy of animals killed at the end of the study.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material, SUBSTANCE 1658/5, in the Sprague-Dawley CFY strain rat was found to be greater than 5000 mg/kg bodyweight.
Executive summary:

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CFY strain rat was found to be greater than 5000 mg/kg bodyweight.

The study was designed to comply with the recommendations of the OECD Guidelines for Testing of Chemicals (1981) No. 401 "Acute Oral Toxicity" referenced as method B1 in Annex V of EEC Commission Directive 84/449/EEC.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The key study was conducted in accordance with GLP and the standardised guidelines OECD Guidelines for Testing of Chemicals (1981) No. 401 "Acute Oral Toxicity" referenced as method B1 in Annex V of EEC Commission Directive 84/449/EEC. It was awarded a reliability score of 2 in accordance with the principles of Klimisch (1997) due to the fact that the study is being used in a read-across capacity. The test was conducted on the analogous substance Zinc Hydroxystannate. The results are considered to be representative of the registered material.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 March 1989 - 16 March 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across to similar substance. Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Justification for type of information:
See read-across justification in Section 13.
Reason / purpose:
other: Target substance
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 – 10 weeks
- Weight at study initiation: Males 219 - 259g; Females 228 – 251g
- Housing: The animals were housed in groups of up to five by sex in solid floor, polypropylene cages, with sawdust bedding.
- Diet (e.g. ad libitum): ad libitum. With the exception of the exposure period, free access to food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.) was allowed throughout the study.
- Water (e.g. ad libitum): ad libitum. With the exception of the exposure period, free access to mains drinking water was allowed throughout the study.
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 21°C
- Humidity (%):46 - 60% relative
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

IN-LIFE DATES: From: To: 2 March 1989 – 16 March 1989
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
INHALATION EXPOSURE
a) Atmosphere Generation
A dust atmosphere was produced using a Wright Dust Feed, controlled by a variable speed motor with the outlet nozzle located at the top of the exposure chamber.
The cylindrical exposure chamber has a volume of approximately 40 litres. The concentration within the exposure chamber was controlled by adjusting the speed of the motor and the air flow rate through the chamber. The extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system.
Compressed air was supplied by means of a Gast 2HBB-10-P25Y oil free compressor and was passed through a water trap and respiratory quality filters which removed particulate material above 0.005 µm before it was introduced to the nebuliser.
b) Exposure Procedure
Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring. Only the nose of the animal was exposed to the test atmosphere.
A single group of ten rats (five males and five females) was exposed to an atmosphere of the test material for a period of four hours. A target concentration of 5 mg/litre was used for the exposure. No deaths occurred and therefore no further levels were required.
c) Exposure Chamber Temperature
The temperature inside the exposure chamber was measured by a mercury thermometer located in a vacant port in the animals' breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period
d) Exposure Chamber Atmosphere Concentration
The chamber concentration was estimated at regular intervals during the exposure period. The gravimetric method used, employed glass fibre filters (Gelman type A/E 25 mm) placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals' breathing zone. Exposure chamber air was drawn through the filter at a measured rate using a vacuum pump for a suitable time period.
Each filter was weighed before and after sampling in order to calculate the weight of collected test material. The difference in the two weights divided by the volume of atmosphere sampled was the chamber concentration.
The nominal chamber concentration was calculated as follows:

Nominal concentration (mg/litre) = Weight of test material used (mg) / Total air flow through chamber (litres)

e) Particle Size Distribution
The particle size of the generated atmosphere of the test material inside the exposure chamber was determined twice during the exposure period, after 40 minutes and during the last hour, using a Cascade Impactor. This device consisted of four glass impactor plates and a back up glass fibre filter (Gelman Type A/E, 25 mm) housed in an aluminium sampler. The sampler was temporarily sealed in a vacant port in the animals' breathing zone. Exposure chamber air was drawn through the Cascade Impactor using a vacuum pump for a suitable time period.
The impactor plates were weighed before and after sampling and the weight of test material, collected on each stage, calculated by difference. From the results obtained the weight distribution of particles in the size range > 13 µm, 4.0 - 13 µm, 1.7 - 4.0 µm and < 1.7 µm was calculated.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
The actual concentration of the test material was measured at least every 15 minutes during each exposure period.
The mean value obtained was 4.35 mg/litre (standard deviation of 1.28, nominal mg/litre 27.4)
No. of animals per sex per dose:
5 male and 5 female
Control animals:
no
Details on study design:
Observation of the Animals
All animals were observed, for clinical signs, at hourly intervals during the exposure, one hour after termination of the exposure and subsequently once daily for 14 days. Any deaths and evidence of overt toxicity were recorded at each observation. Additional death checks were performed at appropriate intervals.
Individual bodyweights were recorded on the day of exposure, days 7 and 14 and at death.
At the end of the 14 day observation period, the animals were killed by intraperitoneal overdose of sodium pentobarbitone (Euthatal, 200 mg/mL, May & Baker Limited, Dagenham, Essex, U.K.). All animals were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.
Statistics:
Evaluation of Data
Using the mortality data obtained, an estimate of the acute inhalation median lethal concentration (LC50) of the test material was made.
Clinical observations, bodyweight and necropsy data were examined for any adverse but non-lethal effects resulting from treatment.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.35 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No deaths occurred
Clinical signs:
other: Isolated incidents of hunched posture, pilo-erection and occasional body tremors were noted following removal from the exposure chamber, with an isolated incident of hunched posture one hour later. All other effects noted during this period were considere
Body weight:
All animals showed expected gain in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy of animals killed at the end of the study.

 Exposure Chamber Atmosphere Concentration:

Atmosphere Concentration

Group Number

Mean Achieved (mg/litre)

Standard Deviation

Nominal (mg/litre)

1

4.35

1.28

27.4

 

Particle Size Distribution:

Group Number

Respirable Fraction (<4µm)

Mean Mass Median % Aerodynamic Diameter (µm)

Geometric Standard Deviation (µm)

1

72.2

2.9

0.58

 

Mortality Data:

Group Number

Mean Achieved Atmosphere Concentration (mg/litre)

Deaths

Male

Female

Total

1

4.35

0/5

0/5

0/10

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute inhalation LC50 of the test material in the Sprague-Dawley CFY rat was greater than 4.35 mg/litre.
Executive summary:

The acute inhalation LC50 of the test material in the Sprague-Dawley CFY rat was greater than 4.35 mg/litre. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 403 "Acute Inhalation Toxicity" referenced as method B2 in Annex V of EEC Commission Directive 84/449/EEC

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The key study was conducted in accordance with GLP and the standardised guidelines OECD Guidelines for Testing of Chemicals (1981) No. 403 "Acute Inhalation Toxicity" referenced as method B2 in Annex V of EEC Commission Directive 84/449/EEC. It was awarded a reliability score of 2 in accordance with the principles of Klimisch (1997) due to the fact that the study is being used in a read-across capacity. The test was conducted on the analogous substance Zinc Hydroxystannate. The results are considered to be representative of the registered material.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – inhalation endpoint
Only one study available.

Justification for classification or non-classification

Acute Oral Toxicity

The acute oral median lethal dose (LD50) of the test material in the rat was found to be greater than 5000 mg/kg bodyweight.In accordance with Annex I, Regulation 1272/2008, the test material does not require classification as it does not meet the criteria.

 

Acute Inhalation Toxicity

The acute inhalation LC50 of the test material in the rat was greater than 4.35 mg/litre.In accordance with Annex I, Regulation 1272/2008, the test material does not require classification as it does not meet the criteria.