Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Appraisal of the safety of chemicals in foods, drugs and cosmetics, by FDA (US), 1959
GLP compliance:
no
Remarks:
Study performed before implementation of GLP
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl]
EC Number:
930-947-3
IUPAC Name:
Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl]

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Paderborn, Germany
- Age at study initiation: no data
- Weight at study initiation: 135 - 210 grams
- Fasting period before study: yes, approx. 16 h prior to dosing
- Housing: macrolan plastic cages (measuring 42 x 42 x 14 cm) with wood chips bedding (Ssniff/bedding) supplied by Intermast, Soest, Germany.
- Diet: ad libitum, commercial pellets, Sniff/Intermast-Standard, Soest, Germany
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 45 - 55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
- Test compound applied as a 50% suspension with arachis oil (warmed at about 37°C).
- pH-value of test sample: 6.0
Doses:
2, 2.52, 3.18, 3.98 g/kg bw
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: frequently closely for gross signs of systemic toxicity and mortalities at intervals on the day of dosing, thereafter at least once daily for an entire period of 14 days
- Frequency of weighing: at start and end (after 14 days)
- Necropsy of survivors performed: yes
- Other examinations performed: Gross necropsies were performed on all animals which died.
Statistics:
Probit analysis

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
< 2 000 mg/kg bw
Remarks on result:
other: 14 d LD50 based on product
Sex:
male/female
Dose descriptor:
LD50
Effect level:
< 1 740 mg/kg bw
Remarks on result:
other: 14 d LD50 based on a.i. (87%)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 570 mg/kg bw
95% CL:
2 350 - 2 790
Remarks on result:
other: 24 h LD50 for produt with 87 % a.i. (this value corresponds to a LD50 of approx. 2236 (95 % CL 2045 - 2427) mg/kg bw for 100% a.i.).
Mortality:
2000 mg/kg bw: after 24 h: 3/10, after 14 d: 7/10
2520 mg/kg bw: after 24 h: 5/10, after 14 d: 8/10
3180 mg/kg bw: after 24 h: 6/10, after 14 d: 10/10
3980 mg/kg bw: after 24 h: 9/10, after 14 d: 10/10

For more details see "Remarks on results including tables and figures."
Clinical signs:
- The sample induced in the tested dosages obvious decreased activity, reduced pain reaction, light tremor and twitches, obvious disturbance in coordination, abnormal body posture, decreased grip- and limp tone, diarrhea and piloerection. Further on in the higher dosages from 2520 mg/kg bw upwards the animals showed emaciated flanks and ptosis.
- The described symptons were observed about 20 minutes after the application and held on partly for 24 hours. Afterwards all animals showed a normal dispositon.
Body weight:
- Normal body weight gains
Gross pathology:
- Gross necropsies performed on the animals which died generally exhibited a redness of the gastrointestinal mucous membrane.
- Necropsies performed on the surviving animals at termination exhibited no gross pathological findings.

Any other information on results incl. tables

Table 1: Number of animals dead (total number of animals: 5 males, 5 females per dose)

Dose (mg/kg bw)

Mortality after  24 h(# dead/total)

Mortality after  14 d(# dead/total)

Time range of deaths

Male

Female

Combined

Male

Female

Combined

2000

2/5

1/5

3/10

4/5

3/5

7/10

24 h – 3 d

2520

2/5

3/5

5/10

3/5

5/5

8/10

24 h – 3 d

3180

2/5

4/5

6/10

5/5

5/5

10/10

 24 h – 48 h

3980

5/5

4/5

9/10

5/5

5/5

10/10

 24 h – 48 h

Applicant's summary and conclusion

Interpretation of results:
sligthly toxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
On the basis of the results obtained after a single oral administration, the oral LD50 after 14 d of the test article Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl] was determined to be < 2000 mg/kg bw for product with 87 % a.i. (this value corresponds to a LD50 of approx. < 1740 mg/kg bw for 100% a.i.). No significant effects on body weight were observed. Decreased activity, reduced pain reaction, light tremor and twitches, obvious disturbance in coordination, abnormal body posture, decreased grip- and limp tone, diarrhea and piloerection were observed about 20 minutes after application and held on partly for 24 hours. Afterwards all animals showed a normal disposition. From doses 2520 mg/kg bw upwards the animals showed in addition emaciated flanks and ptosis.
Therefore the test substance was judged to be slightly toxic based on the LD50 in males and females.
Executive summary:

In an acute oral toxicity study in accordance with the Appraisal of the safety of chemicals in foods, drugs and cosmetics, by FDA (US) 1959, groups of fasted male and female young adult Wistar rats were given a single oral dose of Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl] at doses of 2000, 2520, 3180, 3980 mg/kg bw and observed for 14 days. The substance was administered as 50% suspension in arachis oil warmed at about 37°C.

In the dose groups 2000, 2520, 3180, 3980 mg/kg bw 30, 50, 60, and 90 % of animals died after 24 hours, respectively. After 14 days 70, 80, and 100 % of animals died, respectively. In the dose group 2000 and 2520 mg/kg bw animals were found dead between 24 h and 3 days. In the two highest dose groups animals were found dead on the first 24 or 48 hours after application.

No effects on body weight were observed. Decreased activity, reduced pain reaction, light tremor and twitches, obvious disturbance in coordination, abnormal body posture, decreased grip- and limp tone, diarrhea and piloerection were observed about 20 minutes after application and held on partly for 24 hours. Afterwards all animals showed a normal disposition. At doses from 2520 mg/kg bw upwards the animals showed in addition emaciated flanks and ptosis. Gross necropsies performed on the animals which died generally exhibited a redness of the gastrointestinal mucous membrane. Necropsies performed on the surviving animals at termination exhibited no gross pathological findings.

Oral LD50(14 days) Males/Females: < 2000 mg/kg bw.

No information on content of active ingredient of the test substance in the study report. However, according to producer information the test substance has 87 % a.i., therefore the LD50 refering to 100 % a.i. is < 1740 mg/kg bw.

In addition to the 14 d LD50, a 24 h LD50 (Males/Females) of 2570 (95 % CL 2350 - 2790) mg/kg bw was calculated for the product with 87 % a.i. (this value corresponds to a LD50 of approx. 2236 (95 % CL 2045 - 2427) mg/kg bw) for 100% a.i.).

The test substance Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl] was judged to be slightly toxic based on the oral LD50 (14 days) in male and female rats.