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Administrative data

Description of key information

The LD50 for acute oral toxicity is 420 mg/kg bw (RL 2, rat). The acute dermal toxicity is reported with a LD50 of 195 mg/kg bw (RL 2, rabbit) as well as the toxicity via inhalation is characterised by a LC50 of 500 mg/m³ (RL 1, rat).

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:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose:
reference to same study
Principles of method if other than guideline:
Method: acute oral toxicity test
Screening acc. to Smyth et al., 1962 (animals non-fasted, no necropsy is reported)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: in-house breeding
- Age at study initiation: 4 to 5 weeks
- Weight at study initiation: 90 to 120 g
- Fasting period before study: no
- Diet: Rockland rat diet

Route of administration:
oral: gavage
Vehicle:
other: Test substance probably applied in dilution, no data
Doses:
4 doses in a logarithmic series (factor 2) (acc. to Smyth et al. 1962)
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
420 mg/kg bw

LD50 value is given as 0.54 ml/kg bw (conversion to mg/kg bw was done using the density d= 0.78 g/ccm). Fiducial range values (+/- 1.96 S.D.) were from about 280 - 610 mg/kg bw.

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Single application of a range of doses of the test item to male Wistar rats resulted in a LD50 = 420 mg/kg bw.
Executive summary:

Male Wistar rats (5 rats/sex/dose) were subjected to test acute oral toxicity. The test item (purity not mentioned) was administered by gavage to non-fasted animals in 4 different dose levels (logarithmic series) and were observed for further 14 days. The results obtained led to a LD50 = 420 mg/kg bw (Carpenter et al., 1974).

This published acute oral toxcicity study is, together with methodological details given in other publications of the group, performed well and basic data are given, thus the study can be juged reliable with restrictions (RL 2).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
420 mg/kg bw
Quality of whole database:
comprehensive database, many studies of limited reliability due to insufficient documentation, but overall comparable results

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:
From 7 MAR 1986 to 7 MAY 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Principles of method if other than guideline:
Method:
acute inhalation toxicity
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd.
- Females (if applicable) nulliparous and non-pregnant: no data
- Age at study initiation: no data
- Weight at study initiation: ca. 200 g
- Fasting period before study: no
- Housing: 5 per sex per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 43-49
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
TEST ATMOSPHERE
- Brief description of analytical method used:
Sampling: 5 samples were withdrawn through an acetone-containing absorption trap. 
Analysis: GC-FID analysis
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Test concentrations (analytical): 0.35, 0.51, 0.73, and 2.27 mg/l (45.5, 66, 95, and 295 ppm)
Test concentrations (nominal): 0.46, 0.77, 1.02, 4.93 mg/l ( 60, 100, 133, 640 ppm)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: continuously during exposure, at least twice daily during the observation period
- Frequency of weighing: daily
- Necropsy of survivors performed: yes
Statistics:
LC50 was calculated by the log probit method of Miller and Tainter.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.5 mg/L air
Exp. duration:
4 h
Mortality:
see table
Clinical signs:
other: - abnormal breathing, restlessness, signs of irritation, closure of  eyelids, excessive salivation, whole-body tremor, clonic convulsions,  death  - No symptoms were observed any more in surviving animals after 4 days.
Gross pathology:
- In deceased animals: hyperemic congestion of the lung.
- Surviving animals: no particular findings.

MORTALITY
               male      female
====================================
   0 mg/l    0/5          0/5   
0.35 mg/l    0/5          0/5
0.51 mg/l    4/5          2/5 (within 3 - 24 h)
0.73 mg/l    5/5          5/5 (within 2.5 - 4 h)
2.27 mg/l    5/5          5/5 (within 1 h)
====================================
LC50 = 0.5 mg/l (66 ppm)

Interpretation of results:
Category 1 based on GHS criteria
Conclusions:
Acute inhalation toxicity was tested for the test item (Tri-n-butylamine). Inhalation of 0.51 mg/L of test substance (tributylamin) vapour for 4 hours resulted in the death of 4 out of 5 male and 2 out of 5 female rats, resulting in a LC50 = 0.5 mg/L air.
Executive summary:

Male and female rats (5 rats/sex/dose) were subjected to test acute inhalation toxicity. The animals were exposed (whole body) to vapour at analytical dose levels of 0.35, 0.51, 0.73, and 2.27 mg/L test item (purity 98.5%) for 4 h and were observed for further 14 days.

The animals showed abnormal breathing, restlessness, signs of irritation, closed eyelids, excessive salivation, whole body tremor and clonic convulsions, yet no symptoms were observed any more in surviving animals after 4 days. At a concentration of 0.51 mg/L air 4 out of 5 male and 2 out of 5 female rats died within 3 to 24 h.

The results obtained thus led to a LC50 = 0.5 mg/L air (Pennwalt Corp./HRC, 1987).

This acute inhalation study is performed comparable to guideline studys (OECD TG 403), thus it can be juged reliable (RL 1).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
500 mg/m³
Quality of whole database:
comprehensive database, many studies of limited reliability due to insufficient documentation, but overall comparable results

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose:
reference to same study
Principles of method if other than guideline:
Method: acute dermal toxicity
Screening acc. to Smyth et al., 1962 and Smyth et al., 1954.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.5 to 3.5 kg
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
TEST SITE
- Area of exposure: 1/10 of the body surface
- Type of wrap if used: plastic film
Duration of exposure:
24 h
Doses:
not stated
No. of animals per sex per dose:
4
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
195 mg/kg bw

LD50 value is given as 0.25 ml/kg bw (conversion to mg/kg bw was done using the density d= 0.78 g/ccm). Fiducial range values (+/- 1.96 S.D.) were from about 120 - 316 mg/kg bw.

No further data e.g. on clinical signs or body weight were recorded.

Interpretation of results:
Category 2 based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Testing for acute dermal toxicity led to a LD50 = 195 mg test item (Tributylamin) per kg bw. Due to this value the results were interpreted.
Executive summary:

Male white New Zealand rabbits (4 animals/dose) were subjected to test acute dermal toxicity. The test item (purity not stated) was applied onto 1/10 of the body surface for 24 h under occlusive conditions. The effects were observed for further 14 days.

This single application of the test item to male New Zealand rabbits resulted in a LD50 = 195 mg/kg bw (Carpenter et al., 1974).

This acute dermal toxcicity study is performed well and basic data are given, thus the study can be juged reliable with restrictions (RL 2).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
195 mg/kg bw
Quality of whole database:
sufficient data available for evaluation

Additional information

In a published study male Wistar rats (5 rats/sex/dose) were subjected to test acute oral toxicity. The test item (purity not mentioned) was administered by gavage to non-fasted animals in 4 different dose levels (logarithmic series) and were observed for further 14 days. The results obtained led to a LD50 = 420 mg/kg bw (Carpenter et al., 1974).

This reliable study was selected as key study. Another reliable experimental study performed (RL 2; according to OECD 401, but with deviations) in rats result in a slightly higher LD50 of 780 mg/kg bw, thus supporting previous findings (BASF, 1960). Several studies and published data of lower reliability (RL 3 und RL 4), which were conducted in rats, mice, rabbits, guinea pigs and cats confirmed the reported LD50 values in principle (Sidorin et al., 1984; Ciugudeanu et al., 1985; Din Min, 1977; BASF, 1959).

Male white New Zealand rabbits (4 animals/dose) were subjected to test acute dermal toxicity. The test item was applied onto 1/10 of the body surface for 24 h under occlusive conditions. The effects were observed for further 14 days.

This single application of the test item to male New Zealand rabbits resulted in a LD50 = 195 mg/kg bw (Carpenter et al., 1974).

This study was selected as key study for acute dermal toxicity due to the conservative LD50 value reported. Other reliable sources found a LD50 > 2000 mg/kg bw for the test item, but in another species (rat; BASF, 1981). A tail immersion assay (low reliability, RL 3) revealed a LT50 = 23 min in rats or mice (Sidorin et al., 1984).

Male and female rats (5 rats/sex/dose) were subjected to test acute inhalation toxicity. The animals were exposed (whole body) to vapour at analytical dose levels of 0.35, 0.51, 0.73, and 2.27 mg/L test item (purity 98.5%) for 4 h and were observed for further 14 days.

The animals showed abnormal breathing, restlessness, signs of irritation, closed eyelids, excessive salivation, whole body tremor and clonic convulsions, yet no symptoms were observed any more in surviving animals after 4 days. At a concentration of 0.51 mg/L air 4 out of 5 male and 2 out of 5 female rats died within 3 to 24 h. The results obtained thus led to a LC50 = 0.5 mg/L air (Pennwalt Corp./HRC, 1987).

This reliable study was selected as key study.

Another reliable source reported a similar LC50 of 690 mg/m³ air (BASF, 1983, RL 2). Additional supporting findings in studies of lower reliability are given as LC50 = 580 mg/m³ air (rat; Carpenter et al., 1974), LT0 = 50 min (rat, Carpenter et al., 1974), EC0 = 126 mg/m³ air (only 2 h exposure, in rats or mice; Sidorin et al., 1984), LC50 = 1000 mg/m³ (rat; Taminco file Bioserach(1976)), LC50 = 18000 mg/m³ (Arkema, 1976; 1 h, rat) or the results reported on short term risk inhalation tests (BASF, 1960).

Other routes of application examined gave the following results. Reports of low reliability present a LD50 = 107 mg/kg bw (intra peritoneal, in rats or mice; Sidorin et al., 1984) as well as a LDLo in the range of 310 - 390 mg/kg bw and a LD100 of 780 mg/kg bw (subcutaneous, rat; Hanzlik, 1923).


Justification for classification or non-classification

Based on the requirements of Regulation (EC) No 1272/2008 and an oral LD50 of 420 mg/kg bw in experimental animals tributylamine should be classified as acutely oral toxic category IV.

Based on the available data, which indicate the potential of acute dermal toxicity (LD50 of 195 mg/kg bw) tributylamine should be classified as acutely dermal toxic category II.

The given value of LC50 = 500 mg/m³ air results in a classification for acute toxicity via inhalation into toxicity category I according to Regulation (EC) No 1272/2008.