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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
13 Jun - 07 Jul 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Read across justification: Both target and source chemicals are fatty nitrogen derived amines with structural similarities. The target and source chemicals have similarities in their toxicity potentials based on the findings of in-silico tool DEREK. The result of the analogue approach is supported by the hazard characterization of the fatty nitrogen derived ether amines category 1 of US EPA HPV Program.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Armeen C

Test animals

Species:
rat
Strain:
other: BOR: WISW; SPF TNO
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Firma Winkelmann, Versuchstierzucht, 4791 Borchen 1, Gartenstraße 300, Germany
- Weight at study initiation: males: 170.1 - 190.8 g; females: 140.0 - 162.6 g
- Fasting period before study: The day before treatment, the animals were fasted for a period of 16 hours and received food 4 hours after treatment.
- Housing: in Makrolone cages (type III), max. 5 animals per cage
- Diet (e.g. ad libitum): pellets, Ssniff-R diet for rats (Ssniff Versuchstier-Diäten GmbH, 4770 Soest, Germany)
- Water (e.g. ad libitum): tap water; ad libitum; analytical controls were made periodically
- Acclimation period: approx. 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: oleum arachidis
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% dilution of the test substance in oleum arachidis; pH 8.1
Doses:
range finding study: 1000, 2500, 5000 mg/kg
main study: 500, 1000, 1500, 2000 mg/kg
No. of animals per sex per dose:
range finding study: 2 female animals per dose
main study: 5 animals per sex per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs: 20 min, 1 + 2 h, 3 + 6 h, 24 h, 48 h, 72 h and 7/14 d after treatment; weighing: at day 0 and at day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination of the main organs
Statistics:
The LD50 was calculated according to a Probit Analysis, Finney´s method. (Probit Analysis, 3rd edition, Cambridge 1971)

Results and discussion

Preliminary study:
range finding study:
1000 mg/kg: 1/2 (3 days after application)
2500 mg/kg: 2/2 (4 days after application)
5000 mg/kg: 2/2 (4 days after application)
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 300 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
1 240 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
1 388 mg/kg bw
95% CL:
1 119 - 4 440
Mortality:
500 mg/kg: male: 1/5; female: 0/5 (48 hours after administration: one male animal died)
1000 mg/kg: male: 1/5; female: 1/5 (48 hours after administration: one male animal died; 5 days after administration: one female animal died)
1500 mg/kg: male: 2/5; female: 2/5 (48 hours after administration: one male and one female animal died; 5 days after administration: a further male and female animal died)
2000 mg/kg: male: 5/5; female: 5/5 (48 hours after application: 2 male animals and one female died; 5 days after application: all males were died; 7/14 days after application: all females were died)
Clinical signs:
at all doses: reduced consciousness with apathy, abnormal position and poor posture, loss of coordination (reduced excitability), cyanosis, limited but extreme salivation, piloerection, slightly reduced breathing rate, slight hypothermia
The clinical signs were observed 20 minutes after administration and were persisted up to 7 days after aadministration. All surviving animals showed a normal habitus during the last 7 days of the observation period.
Body weight:
All surviving animals showed normal body weight gain.
Gross pathology:
Macroscopic examinations of died animals (during the study period) showed slight redness and accumulation of fluid in the gastrointestinal tract.
Macroscopic examinations of sacrificed animals (at the end of the study) revealed no abnormalities of the main organs.

Any other information on results incl. tables

The analogue approach using coco alkylamines as source chemical is justified:

a.   Both target and source chemicals are fatty nitrogen derived amines with structural similarities.Therefore, it can be assumed that target and source chemicals share the same toxic mode action.

b.   The target and source chemicals have similarities in their toxicity potentials.The findings from in-silico tool DEREK are comparable for target and source chemicals. No toxicological concerns are identified based on their structures.

c.    The result of the analogue approach on the endpoint of acute oral toxicity is supported by the hazard characterization of the fatty nitrogen derived ether amines category 1 evaluated by US EPA through the High Production Volume (HPV) Program.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the analogue approach using coco alkylamine as read-across supporting substance, the median lethal dose (LD 50) of the target substance is considered to be 1300 mg/kg/bw.
Executive summary:

The acute oral toxicity of the target substance was assessed based on the read-across appoach using coco alkylamines as read-across supporting substance.

In an OECD TG 401 study, the test material Armeen C, a clear light-yellow, oily liquid, was orally applied to Wistar rats at doses of 500, 1000, 1500 and 2000 mg/kg bw. The substance was applied as a 20% solution in peanut oil (pH 8.1). At 500 mg/kg bw, two males died 5 and 7 days after treatment, respectively. At 1000 mg/kg bw, two males and two females died between days 5-14 (40%). At 1500 mg/kg bw, four males and four females and at 2000 mg/kg bw (80%), ten males and nine females died between days 5-14 (95%). An LD50 of 1300 mg/kg bw (1240 mg for male and 1390 mg for female rats) was calculated (probit analysis after Finney). Clinical signs, observed in all treatment groups, included apathia, slight to pronounced irregular postures, uncoordinated movements, reduced reflexes, cyanosis, salivation, piloerection, slightly reduced breathing rate and some cases of slight hypothermia. Symptoms started from 20 minutes after dosing on and were present until death or up to 7 days in survivors. After dissection of dead animals, slight reddening and liquid congregations were detected in the gastrointestinal tract. There were no pathological findings in the surviving animals.

Based on the analogue approach using coco alkylamine as read-across supporting substance, the median lethal dose (LD 50) of the target substance is considered to be 1300 mg/kg/bw.