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Description of key information

Acute inhalation toxicity: LC50 > 20mg/L (= 20000 mg/m3) (OECD 403, K, Rel.1)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
7 June to 3 August 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted according to OECD Guideline 403 without deviation.
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
traditional method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animals were received from Charles River (UK) Limited, Manston Road, Margate, Kent, England on 7 June 1994.
- Weight on arrival to the laboratory: 120-150 g
- Housing: Rats were housed 5 animals per sex per cage in suspended polypropylene cages with detachable stainless steel tops and bottoms.
- Diet: Rat and Mouse (Modified) No.1 Diet SQC Expanded (supplied by Special Diets Services Limited, Stepfield, Witham, Essex), ad libitum.
- Water: Animals had access to domestic mains quality drinking water, ad libitum.
- Food and water were available ad libitum except during the 4 h exposure period.
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 20 °C ± 2 °C
- Humidity: 55% ± 10%
- Air changes: 15-20 air changes per hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: 7 June to 3 August 1994
Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
Animals did not require conditioning prior to dosing as restraint procedures during whole body dosing are considered not to adversely affect the outcome of the study.

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 100 L all glass exposure chamber
- Exposure chamber volume: 100 L
- Method of holding animals in test chamber: During exposure to the test item the animals were confined within stainless steel mesh compartments within the exposure chamber.
- Test atmosphere was generated as follows:
60 mL of liquid test item was placed in a polypropylene syringe and cooled using ice packs. The syringe was placed on a syringe pump and a feed line connected to a dreschel flask.
- Source and rate of air: Pre-warmed air was generated by passing 10 L/min compressed air through a nylon heating coil placed in a water bath at approximately 30 °C. The warmed air was passed into the dreschel flask and assisted the vaporisation of the liquid test item. The gas/air mixture was then diluted with an additional 15 L/min compressed air and ducted to the inlet port of the exposure chamber. The required concentration of test gas was maintained by regulating the liquid feed to the dreschel flask.
- Treatment of exhaust air: Following a 'single pass' through the exposure chamber the contaminated air was extracted from the chamber and then exhausted to the external atmosphere.
- Chamber air flow rates: Chamber air flow rates were monitored continually using flowmeters and recorded at 30 min intervals throughout the exposure period. The value recorded was a constant 25 L/min.

TEST ATMOSPHERE
- During the exposure period the temperature within the exposure chamber was measured by a mercury thermometer located at the animals' breathing zone whilst the relative humidity was monitored using wet/dry bulb mercury thermometers. The chamber temperature and relative humidity were measured at 30 min intervals throughout the exposure period. The mean values recorded for temperature and relative humidity were 23 °C and 52 % respectively.

ATMOSPHERIC CHARACTERISATION
The nominal chamber concentration was estimated using the following equation:
Nominal concentration (mg/Litre) = Weight of material used (mg) / Total air flow through chamber (litres)
Concentration: The nominal concentration was calculated based on the total usage of material and volume of dilution air used, and was calculated to be 20 mg/L.
The total usage was derived from the liquid volume used and the specific gravity of the liquid 1.56 g/mL at 25 °C).
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
20 mg/L (nominal concentration)
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: All the rats were observed continuously throughout the exposure period, and any clinical signs noted were recorded at 30 min intervals. Animals were also observed immediately after exposure and for the first 1-2 h post dosing and thereafter at least once and normally twice daily during the subsequent 14 day observation period. The onset, intensity and duration of any signs observed were recorded.
- Frequency of weighing: All the rats were weighed immediately before dosing and on Days 2, 3, 4, 7, 10 and 14 post exposure.
- Necropsy of survivors performed: Yes; At the end of the 14 day observation period all the animals were sacrificed by carbon dioxide asphyxiation and subjected to a detailed macroscopic post mortem examination.
Each rat was examined externally prior to opening the abdominal and thoracic cavities. Any gross lesions observed were recorded in descriptive terms, including location(s), size (mm), colour and number. The respiratory tract was subjected to detailed macroscopic examination for signs of irritancy or local toxicity. All organs were examined in situ.
Lung:Body Weight Ratio: The lungs of each animal were removed and weighed to allow calculation of lung:body weight ratio.
On completion of the necropsy the animals' carcasses were disposed of; no tissues were retained.
Statistics:
None
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 20 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
There were no unscheduled deaths during the study.
Clinical signs:
other: - Clinical signs during exposure were limited to laboured respiration. - Clinical signs during post exposure observations included laboured respiration, subdued behaviour, unkempt appearance, eyes which were red with a sticky discharge and animals were co
Body weight:
Males and females showed marked body weight losses and reduced body weight gain during the first week of the observation period. Body weight gains were within normal ranges for the duration of the second week of the observation period. This effect was considered to be related to treatment with test item.
Gross pathology:
Necropsy findings for males and females were similar and included incidences of pale and mottled lungs, mottled kidneys, darkened spleens and pale livers. These findings were considered to be related to treatment with test item.
Other findings:
Lung:Body Weight Ratio: Absolute lung weights and lung:body weight ratios were within normal ranges.

Table 7.2.2/1: Exposure Chamber Concentration

 

Total Amount of Compound Used (g)a

Total Volume of Air Used (Litre)

Nominal Exposure Chamber Concentration (mg/L)

117

5950

20

 

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

a= Total amount of compound used (g) derived from total volume of liquid at 1.56 g/mL, specific gravity at 25 °C.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the inhalation LC50 for test item is higher than 20 mg/L (nominal concentration) in rats.
Executive summary:

In an acute inhalation toxicity study (limit test) performed according to OECD Guideline 403 and in compliance with GLP, one group of Sprague Dawley rats (5 animals/sex/dose) was exposed by inhalation (whole body exposure) to test gas for a single 4 h period at nominal concentrations of 20 mg/L. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

There were no unscheduled deaths during the study. Clinical signs during exposure were limited to laboured respiration. Clinical signs during post exposure observations included laboured respiration, subdued behaviour, unkempt appearance, eyes which were red with a sticky discharge and animals were cold to the touch. Incidences of hunched posture and dull eyes were also recorded. All animals returned to normal after Day 7 of the observation period. There were no other signs considered to be of toxicological importance. Males and females showed marked body weight losses and reduced body weight gain during the first week of the observation period. Body weight gains were within normal ranges for the duration of the second week of the observation period. This effect was considered to be related to treatment with test item. Necropsy findings for males and females were similar and included incidences of pale and mottled lungs, mottled kidneys, darkened spleens and pale livers. These findings were considered to be related to treatment with test item. Absolute lung weights and lung:body weight ratios were within normal ranges.

 

Under the test conditions, the inhalation LC50 for test item is higher than 20 mg/L (nominal concentration) i.e. > 20000 mg/m3 in rats.

This study is considered as acceptable and satisfies the requirement to cover the acute toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
20 000 mg/m³
Quality of whole database:
The key study performed on the registered substance in rats was GLP and was compliant with OECD Test guideline No 403 (Klimisch 1). This study was considered sufficiently robust to cover this endpoint.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A key study was identified (Kieran, 1995, rel. 1). In this acute inhalation toxicity study (limit test) performed according to OECD Guideline 403 and in compliance with GLP, a group Sprague Dawley rats (5 animals/sex/dose) were exposed by inhalation - whole body exposure to test gas for a single 4 h periodat nominal concentrations of 20 mg/L. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

There were no unscheduled deaths during the study. Clinical signs during exposure were limited to laboured respiration. Clinical signs during post exposure observations included laboured respiration, subdued behaviour, unkempt appearance, eyes which were red with a sticky discharge and animals were cold to the touch. Incidences of hunched posture and dull eyes were also recorded. All animals returned to normal after Day 7 of the observation period. There were no other signs considered to be of toxicological importance. Males and females showed marked body weight losses and reduced body weight gain during the first week of the observation period. Body weight gains were within normal ranges for the duration of the second week of the observation period. This effect was considered to be related to treatment with test item. Necropsy findings for males and females were similar and included incidences of pale and mottled lungs, mottled kidneys, darkened spleens and pale livers. These findings were considered to be related to treatment with test item. Absolute lung weights and lung:body weight ratios were within normal ranges.

 

Under the test conditions, the inhalation LC50 for test item is higher than 20 mg/L (nominal concentration) in rats.

Inhalation LC50 > 20 mg/L i.e. 20000 mg/m3.

Additional information

Inhalation route was prefer to the oral route based on the physicochemical properties of the test substance. Indeed, with a vapour pressure of 84 kPa at 20°C, the test substance is volatile at ambient temperature. Therefore, inhalation route is the main expected route of exposure.

Justification for classification or non-classification

Harmonized classification:

The substance does not have an harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity (Inhalation):

Based on the available information, the substance is:

- not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 20000 mg/m3

- not classified in Category 5 according to the UN GHS since there is no reliable evidence indicating that the substance is toxic above 20000 mg/m3 (GHS criteria not met).

Acute toxicity (Oral):

No information was available.

Acute toxicity (Dermal):

No information was available.

Specific target organ toxicity: single exposure (Inhalation):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, inhalation are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (inhalation - vapours) for a Category 1 classification (C≤ 10 mg/L) and for a Category 2 classification (20 mg/L ≥C > 10 mg/L). No classification is therefore required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects and respiratory tract irritation were not observed in the acute inhalation toxicity study.

Specific target organ toxicity: single exposure (Oral):

No information was available.

Specific target organ toxicity: single exposure (Dermal):

No information was available.