Registration Dossier

Administrative data

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: Meets generally accepted scientific standards, well documented and acceptable for assessment. Restriction: Report not evaluated by QAU.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name: Tridecylamine (CAS No. 86089-17-0)
- Degree of purity >99%

Test animals

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

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose/head only
Vehicle:
other: supply 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.

Results and discussion

Effect levelsopen allclose all
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:
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 animals until day 1, reduced general state in 4/4 animals until days 1-2).
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.