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Administrative data

Description of key information

The LD50 values for this material have been repeatedly tested orally, dermally and by inhalation.  All study groups show simliar values for each exposure type, therefore there is much supporting evidence to back up the key value studies used to classify the substance as very toxic even though in many cases full details of test methods are not available

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment. Reliability assessment as per that quoted in IUCLID 4 (2000) data review
Principles of method if other than guideline:
16 animals assigned to 4 groups were dosed via intragastric intubation with with different levels of TEL dissolved in peanut oil. Mortality data was collected over a period of 14 days and the LC50 value determined by producing a response curve
GLP compliance:
not specified
Test type:
fixed dose procedure
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
8 males (350 - 425 grams in weight) and 8 female (150 - 250 grams in weight)
Temperature and light controlled confined room with 12 hour light cycles with no contact to sunlight or UV light
Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
TEL at 7.32 mg/ml of pure peanut oil
2 ml of oil administered per animal
Single dose then observation for 14 days to collect mortality data
Doses:
4 groups dosed at 10/13/16.9/21.97 mg TEL/kg bw
No. of animals per sex per dose:
Equal number of males and females per group
Control animals:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
14.18 mg/kg bw
Based on:
test mat.
95% CL:
> 12.62 - < 15.93
Mortality:
Mortalities after 14 days observed were:
1 of 4 @ 10 mg/kg
0 of 4 @ 13 mg/kg
4 of 4 @ 16.9 mg/kg
4 of 4 @ 21.97 mg/kg

All animals displayed neurological signs including lethargy, irritability and ataxia from day 2. Violent trembling and aggressiveness then followed from day 5 with convulsions and death from day 6. These signs appeared sooner in those animals receiving the higher doses

Interpretation of results:
very toxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
An LD50 value of 14.18 mg/kg is reported in rats
Executive summary:

Schroeder (1972) showed the oral LD50 of TEL to be 14.18mg/kg bw. The research was based on a sample group of 16 rats in four groups or four with each group receiving a different dose level of TEL. All animals displayed neurological signs including lethargy, irritability, ataxia, violent trembling and aggressiveness. In animals dosed at the higher two dose levels death followed from day 6 and all 8 animals died by the end of the study on day 14. The LD100 was 16.9mg/kg bw

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
14.18 mg/kg bw

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment. Reliability assessment as per that quoted in IUCLID 4 (2000) data review
Principles of method if other than guideline:
Inhalation exposures were carried out in a glass chamber. Groups of 4 rats were exposed to TEL vapour with only their heads in contact with the vapour. Pure solutions of TEL were injected into the chamber with the air flow maintained at 50 litres per minute. Samples of air were taken at intervals during the 60 minute exposure period and analysed for TEL content. Lethal doses and their 95% confidence limits were calculated by reported method
GLP compliance:
no
Remarks:
Test completed before GLP implemented
Species:
rat
Strain:
other: Albino
Sex:
not specified
Details on test animals and environmental conditions:
175-230 g in weight
Route of administration:
inhalation
Type of inhalation exposure:
head only
Vehicle:
air
Details on inhalation exposure:
Pure TEL in 50 l / min air flow
7 sample groups of 12 -20 rats with each group receiving a different dose level of TEL
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Polargraphical measurement of TEL content after conversion to lead chloride
Duration of exposure:
60 min
Concentrations:
0.095 mg/l, 0.19 mg/l, 0.37 mg/l, 0.77 mg/l, 1.58 mg/l, 2.77 mg/l and 4.84 mg/l
No. of animals per sex per dose:
0.095 mg/l: 16
0.19 mg/l: 16
0.37 mg/l: 20
0.77 mg/l: 16
1.58 mg/l: 16
2.77 mg/l: 20
4.84 mg/l: 12
Control animals:
not specified
Dose descriptor:
LC50
Effect level:
ca. 0.85 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
1 h
Dose descriptor:
LC100
Effect level:
< 1.58 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
1 h
Mortality:
0.095 mg/l: 0/16
0.19 mg/l: 0/16
0.37 mg/l: 0/20
0.77 mg/l: 3/16
1.58 mg/l: 16/16
2.77 mg/l: 20/20
4.84 mg/l: 12/12
Clinical signs:
Signs of mild poisoning with slow recovery at low doses

The development of signs of toxicity from inhalation were the same as similar studies with intraveneous dosing. Hyperexcitability and continuous body tremours were observed at doses below the lethal dose.

Interpretation of results:
very toxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
An LC50 value of 0.85 mg/l was determined. An LC100 value of <1.58 mg/l is also reported
Executive summary:

The research was based on 7 sample groups of 12 -20 rats with each group receiving a different dose level of TEL. All animals displayed behaviour changes, signs of mild posioning and some had cyanosis at lower dose rates. All animals dosed at 0.37 mg/l and below survived.

Deaths started to be observed at the 0.77 mg/l dose rate with an LC50 value of 0.85 mg/l determined. Animals dosed at the higher three dose levels all died. The LC100 was reported as 1.58 mg/l.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
850 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
547 mg/kg bw

Additional information

The LD50 values for this material has been assessed in a number of laboratory animal studies involving oral, dermal, and injection administration, and the LC50 assessed following inhalation exposure. All study groups show similar values for each exposure type, therefore there is much supporting evidence to back up the key values used to classify the substance as very toxic even though in many cases full details of test methods are not available.

Schroeder et al. (1972) showed the oral LD50 of TEL to be 14.18 mg/kg bw in rats. The research was based on a sample group of 16 rats in four groups or four with each group receiving a different dose level of TEL by gavage. All animals displayed neurological signs including lethargy, irritability, ataxia, violent trembling and aggressiveness. In animals dosed at the higher dose levels death followed from day 6 and all animals died by the end of the study on day 14. The LD100 was 16.9 mg/kg bw.

Cremer and Callaway (1961) completed the research on the inhalation toxicity of TEL. The research was based on 7 sample groups of 12-20 rats with each group receiving a different dose level of TEL for 1 h. All animals displayed behaviour changes, signs of mild poisoning and some had cyanosis at lower dose rates. All animals dosed at 0.37 mg/L and below survived. Deaths started to be observed at the 0.77 mg/L dose rate with an LC50 value of 0.85 mg/L (equivalent to about 850 mg/m³ air) determined. Animals dosed at the higher three dose levels all died. The LC100 was reported as 1.58 mg/L.

Dermal toxicity studies by Akatsuka (1973a) in various animals gave a range of LDLo values of 547-995 mg/kg bw. Little detail can be found of the methods used. The lowest value (547 mg/kg bw) in dogs has been selected for CSA purposes. Overall, it can be concluded that shortly after acute administration, animals appear lethargic, followed by a longer period of hyperexcitability, aggressiveness and tremors. There then follows a period of hypothermia, uncoordinated behaviour, convulsions, ataxia and/or paralysis. At higher doses death occurs. Central nervous symptom effects, diarrhea, loss of body weight and reduced food intake are also reported.

At least one supporting study also notes that at higher doses, irritability, hyper-mobility, tremours, spasticity and weight loss are likely. Pathological and histopathological changes in the form of damage in the cerebral cortex, the spinal cord, the medulla oblongata, pons and hippocampus are also observed. 

Justification for classification or non-classification

TEL is classified in Annex I of the DSD as R26, R27 and R28 (very toxic by inhalation, in contact with skin and if swallowed, respectively), and would be classified as acutely toxic by all routes of exposure according to EU regulations.