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Administrative data

Description of key information

Acute Toxicity:
- oral: LD50: 820 mg/kg bw, rat, BASF 1970

- no mortality at saturated vapour concentrations, rat, 8h (BASF 1970)


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: Comparable to guideline study with acceptable restrictions (short observation period, brief report)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
observation period only 7 days
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
other: Gassner
Sex:
male/female
Details on test animals and environmental conditions:
no data
Route of administration:
oral: gavage
Vehicle:
other: aqueous emulsion containing polysaccharide (traganth)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.1-20%
Doses:
200, 400, 500, 640, 800, 1000, 1250, 1600 µl/kg bw
No. of animals per sex per dose:
10
Details on study design:
- Duration of observation period following administration: 7 days (400-1600 µl/kg bw) and 10 days (200 µl/kg bw)
- Frequency of observations: at least daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs of toxicity
- LD50 was calculated according to Litchfield-Wilcoxon
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
820 mg/kg bw
Mortality:
First deaths were noted 24 h postdose. Deaths occurred also at later time points, e.g. between days 2 and 7 postdose, in the groups receiving 640 µl/kg bw and higher. In the group at 200 µl/kg bw one death was noted between postdose days 7 and 10.
Higher doses with 10 or 20 vol% of tridecylamine were 100% lethal within 7 days.
Clinical signs:
Dyspnea and restlessness, salivation piloerection, hunched posture were reportedly noted at all dose levels within minutes after dosing. Forced breathing and red encrusted eyes and noses were noted during the days after treatment. No signs were seen from postdose days 7 and 8 onwards.
Gross pathology:
Findings were not discriminated according to dose level.
Findings and incidences in animals that died:
Snouts: bloody smeared snouts (9 cases); bloody smeared and encrusted snouts (22 cases). Ani: bloody smeared ani- diarrhea (7 cases). Stomach, intestine: stomachs filled with TS (3 cases); stomach ectasia (8 cases); distended stomach (18 cases); ectasia in upper gut (1 case); atonic GI tracts (37 cases); putrefaction (2 cases); 1 animal without findings.

Findings and incidences in animals that were sacrificed:
No findings except 2 cases of adhesions.

Mortalities:

Dose

(µl/kg bw)

Test substance

(%)

Mortalities 7 days postdose

Males

Females

Total

200

2

0/10

1/10

1/20

400

4

0/10

0/10

0/20

500

8

1/10

0/10

1/20

640

8

3/10

5/10

8/20

800

8

0/10

8/10

8/20

1000

10

1/10

10/10

11/20

1250

10

10/10

10/10

20/20

1600

20

10/10

10/10

20/20

 

The combined LD50-value was estimated to be 1000 µl/kg bw. This  corresponds to ca. 820 mg/kg bw. The acute toxicity was higher in females (LD50 estimated at 520 mg/kg bw) than in males.

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
There is a steep dose-mortality relation. Combined mortalities of 40 or 55% were noted in the dose range 640 to 1000 µl/kg bw, with 8 - 10 vol% tridecylamine in the administered dose.
The acute toxicity was higher in females (LD50 estimated at 520 mg/kg bw) than in males. The calculated combined male and female LD50-value was approx. 820 mg/kg bw.
Stomach, intestine, and snouts were affected. The symptoms suggest to be related to the corrosive properties of the test substance.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
820 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment. Restriction: Report not evaluated by QAU.
Principles of method if other than guideline:
Study according to a method of the American Society for Testing and Materials, Standard Test Method for Estimating Sensory Irritancy of Airborne Chemicals (ASTM E981). Groups of 4 male Swiss mice were exposed to 3.8, 7.7, 23 and 90 mg/m³ (0.46, 0.93, 2.79 and 10.9 ppm) Tridecylamine vapour for 45 minutes in a head-nose inhalation system. The post-exposure observation period was 7 days.
GLP compliance:
no
Remarks:
The experimental phases of this study were conducted under GLP conditions and the QAU inspected the study. However, the study report was not audited by QAU.
Test type:
other: Respiratory irritation
Limit test:
no
Species:
mouse
Strain:
Swiss
Sex:
male
Details on test animals and environmental conditions:
- Strain: Crl:CD-1
- Age: 7-8 weeks
- Housing: singly in cages type MKI of Becker
- Environment: fully air-conditioned rooms, temperature range 20-24°C, relative humidity 30-70%, 12 hour light/dark rhythm
- Diet: standard rat/mouse/hamster laboratory diet (KLIBA 24-343-4, 10 mm pellets, from Klingentalmühle, Kaiseraugst, Switzerland) ad libitum; drinking water ad libitum
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose/head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: INA 10 (stainless steel construction, BASF AG)
- Exposure chamber volume: approx. 7.5 L
- Method of holding animals in test chamber: body plethysmographs
- Atmosphere generation: Test substance was delivered onto a heated glass vaporizer for each test group. Vapors were mixed with supply air (compressed air).
- Source and rate of air: 1200 L/h (approx. 160 air changes per hour)

TEST ATMOSPHERE
- Brief description of analytical method used: samples of test atmospheres were drawn from the inhalation system into sorbent (2-propanol) and examined using GC/FID (sample volume: 90 - 400 mL; sample frequency: 1 sample per concentration group, 2 samples for the highest concentration group)
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Remarks:
by GC/FID
Duration of exposure:
45 min
Concentrations:
0, 3.8, 7.7, 23, and 90 mg/m³ (analytical)
No. of animals per sex per dose:
4 males
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: A check for dead or moribund animals was made daily. Clinical signs were checked during and after
exposure on exposure day and once per workday during the post-exposure-observation period. The body weight of the animals was checked at random before the test and three times during the post-exposure-observation period.
- Other examinations performed:
Conduct of measurements: the test was started after the animals were placed into the plethysmographs, and was structured in 4 phases: i) adaptation phase lasting 10 min; ii) control phase lasting 15 min to establish normal breathing parameters; iii) exposure phase, lasting 45 min; recovery phase, lasting 15 min.
Respiration measurements: body plethysmographs (BASF AG) with pressure transducers were used. The signals were processed by a "Non invasive respiratory analyzer" (Buxco Electronics) as minute values and transferred to a personal computer for further evaluation using tabular calculation software.
Breathing parameters examined: respiratory rate; tidal volume; inspiration time; expiration time; relaxation time; peak expiratory flow; and minute volume.
Determination of sensory irritation, based on "ASTM: E 981-84: Standard Test Method for Estimating Sensory Irritancy of Airborne Chemicals".
Terminal examination: the animals were sacrificed at the end of the observation period. The lungs were evaluated macroscopically and weighed with trachea (without larynx).
Statistics:
The decrease of the respiration rate was calculated (expressed as percentage depression of normal rate, RR%) for each animal by comparing the rate at an early (minutes 6 to 15 of the exposure phase), intermediate (minutes 21 to 30 of the exposure phase), and late (minutes 36 to 45 of the exposure phase) time of exposure with the normal rate (minutes 6 to 15 of the control phase). Recovery was calculated accordingly (rate at minutes 6 to 15 of the recovery phase compared to normal rate). The mean respiratory depression (RD%) for each test animal and each time interval was calculated
as 100 - RR% . These individual values were used to calculate the RD50 values. Additionally mean RD% for each test groups were calculated using the single animal RR% values.The substance concentration leading to a 50%-depression (RD50) was calculated from the logarithm of the analytical concentration and the decrease of each animal and each early, intermediate, and late time interval. The concentration and 95% confidence interval was estimated by inverse regression.
Sex:
male
Dose descriptor:
other: RD50 early
Effect level:
526 mg/m³ air
Exp. duration:
45 min
Remarks on result:
other: Minutes 6-15 of exposure phase
Sex:
male
Dose descriptor:
other: RD50 middle
Effect level:
37.4 mg/m³ air
95% CL:
>= 22.2 - <= 91.6
Exp. duration:
45 min
Remarks on result:
other: Minutes 21-30 of exposure phase
Sex:
male
Dose descriptor:
other: RD50 late
Effect level:
30.4 mg/m³ air
95% CL:
>= 20.4 - <= 53
Exp. duration:
45 min
Remarks on result:
other: Minutes 36-45 of exposure phase
Mortality:
No mortalities observed.
Clinical signs:
other: Clinical signs were only seen in test group 3 (23 mg/m³; piloerection in 4 animals, reduced general state of one animal until days 6 and 7 of the observation period) and in test group 4 (90 mg/m³; piloerection in 4/4 animals, dragging respiration in 4/4 a
Body weight:
Body weights were decreased in the high dose test group from day 1 until day 7 post exposure, without reaching the p<0.05 level of statistical significance.
Gross pathology:
Focal red discoloration in some lobes of the lung was found in 2/4 high dose animals. No abnormalities were detected in the other animals.
Other findings:
- Organ weights: on day 7 post exposure the absolute lung weights were decreased in the test groups 3 and 4 without reaching the p<0.05 level of statistical significance whereas the lung weights of the animals at 3.8 and 7.7 mg/m³ were comparable to controls. The relative lung weights were comparable in all animal groups.
- Respiratory depression: The time response curves showed a concentration dependent steady decrease of breathing rate throughout the exposure period, with only minimal indication of reversal during the recovery period. Thus, the RD50s calculated from respiration rates measured early, in the middle and late during the exposure period were steadily decreasing. The RD50 was lowest with a value of about 30 mg/m³ ≈ 4 ppm during the last third of the exposure period.

Respiration rate decrease (group means, 4 animals per group):

Test group

Analytical concentration (mg/m³)

Respiration rate decrease (RD%)

early

middle

late

recovery

0

Control

11.6

10.8

12.3

6.6

1

3.8

27.1

20.8

23.7

30.2

2

7.7

34.6

35.0

36.0

39.5

3

23

26.5

36.9

45.7

28.7

4

90

45.7

63.9

63.0

63.5

RD50 values and lower (LCL) and upper (UCL) 95% confidence limits:

RD50 (mg/m³)

LCL

UCL

RD50 (ppm)

early

526

no meaningful result

no meaningful result

63.7

middle

37.4

22.2

91.6

4.53

late

30.4

20.4

53.0

3.68

Interpretation of results:
study cannot be used for classification
Conclusions:
The test substance effects mainly pulmonary irritation in mice. The RD50 is steadily decreasing and is lowest with a value of about 30 mg/m³ ≈ 4 ppm during the last third of the exposure period. Exposure of mice to 23 or 90 mg/m³ for a period of 45 minutes caused clinical signs during exposure (piloerection and depressed breathing rate during exposure). Poor general state and reduced body weights were seen in animals exposed to 90 mg/m³.
Pathology revealed focal red discoloration in some lobes of the lung in 2/4 high dose animals. Although no changes in lung weights occurred (possibly due to measurement only after 7 days post exposure), the macroscopic lung findings and the time-response relationship of breathing rates suggest that significant pulmonary irritation was present.
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study protocol is in principle similar to OECD TG 403, limited documentation, no analytical monitoring of test atmosphere concentration.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
No analytical verification of test atmosphere concentration. Observation period 7 days
GLP compliance:
no
Test type:
other: Inhalation Risk Test (IRT)
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 460 - 505 g
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
The test demonstrates the toxicity of an atmosphere saturated with vapours of the volatile components of a test substance at the temperature chosen for vapour generation (20 °C).
- Atmosphere generation: a stream of fresh air (200 L/h) was passed through a wash bottle placed into a water bath containing a 5-cm layer of the test substance.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
near saturation (20°C)
No. of animals per sex per dose:
6 males and 6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Observations: animals were observed for clinical signs of toxicity during the exposure and the observation period. At termination the animals were sacrificed and necropsied, including examination of heart, lungs, liver, spleen and kidneys.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
other: no mortalities observed when saturated vapor atmosphere was tested
Mortality:
No mortalities (0/12).
Clinical signs:
other: Irritation to the mucous membranes were noted on the day of exposure. The signs subsided and were absent on the following day.
Gross pathology:
No abnormalities detected.
Interpretation of results:
study cannot be used for classification
Conclusions:
No mortalities (0/12) were observed when rats were exposed to a saturated vapor atmosphere of the test substance for 8 h (Inhalation Risk Test).

Additional information

Oral:

The oral LD50 was 820 mg/kg bw in rats that received aqueous suspension of TDA at dose levels ranging from 0.2 to 1.6 mL/kg bw (BASF AG, 1970). Dyspnoea and restlessness, salivation piloerection, and hunched posture were reportedly noted at all dose levels within few minutes after dosing. Forced breathing and red encrusted eyes and noses were noted during the days after treatment. Signs subsided and were absent from postdose days 7 and 8 onwards. First deaths occurred within 24 hours postdose in the higher dose level groups. One animal of the lowest dose groups died between 7 and 10 days post treatment. Gross pathology revealed bloody smears of the snouts, diarrhoea, adhesions and atonic gastrointestinal tract in many animals. The steep mortality-dose curve and the signs of toxicity suggest that corrosivity of the test substance was the driving element for these effects.

A second test for acute oral toxicity performed by BASF SE in 2018 according to GLP (OECD 423, acute toxic class method) confirmed the LD50 value range. Tridecylamine, branched and linear with the test substance number PSN 18/0023 was tested. Based on 3/3 mortalities at 2000 mg/kg bw and 1/6 mortalities at 300 mg/kg bw, the LD50 is >300 mg/kg bw and <2000 mg/kg bw.

 

Dermal:

There is no acute dermal study known to exist. In accordance with Column 2 of REACH Annex VIII, testing for acute dermal toxicity is not required as studies on skin irritation/corrosion indicate that Tridecylamine is corrosive to the skin.

 

Inhalation:

In a mouse bioassay (BASF AG, 1998) the sensory irritation potential of TDA was studied using the method of the American Society for Testing and Materials, Standard Test Method for Estimating Sensory Irritancy of Airborne Chemicals (ASTM E981). In this test, groups of 4 male Swiss mice were exposed head-only to TDA at 3.8, 7.7, 23 or 90 mg/m3 for 45 minutes. Whilst exposure to 3.8 and 7.7 mg/m3 did not result in any clinical signs, all mice exposed to 23 mg/m³ showed piloerection and one mouse in this group was also in a poor general condition. In the 90 mg/m3 group, all animals had labored breathing, piloerection, and all were in poor general state.

Additional data were available from an inhalation risk test (IRT) which meets generally accepted scientific principles (BASF AG, 1970). The inhalation of a saturated vapor-air mixture for 8 hours caused no mortality. Irritation to the mucous membranes was noted on the day of exposure. The signs subsided and were absent on the following day.

Justification for classification or non-classification

TDA was of moderate acute oral toxicity in rats with an oral LD50 of 820 mg/kg bw.

Based on the results of the acute oral toxicity testing, the test item is classified as harmful if swallowed cat. 4 (H302) according to Regulation (EC) No 1272/2008 (CLP).