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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from a test procedure according to national (US) standards comparable to international guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: US Guideline: Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, FDA, 1959
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
Study performed before implementation of GLP
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS:
- Age: no data
- Sex: males and females
- Weight at study initiation: females: 150 - 170 g, males: 175 - 210 g
- Housing: individual housing in a battery of cages
- Diet: ad libitum, standardised laboratory diest Ssniff/Intermast
- Water: ad libitum
- Fasting period before study: 16 hours

ENVIRONMENTAL CONDITIONS:
- Roomtemperature: 22 +/- 1° C
- Relative humidity: 45 - 55 %
- Illumination: 12 hours daily

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
applied volumes: 0.75 - 2.1 ml/animal (depending on individual body weight and designated dose level)
Test substance was applied in the original state (aqueous solution, a.i. according to producer information 30 %) as delivered by the sponsor.
Doses:
5.0, 6.3, 7.94, 10.0 ml/kg bw, test substance applied as delivered by the sponsor (30 % a.i.)
No. of animals per sex per dose:
5 females
5 males
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 d
- Body weights were recorded before treatment (day 0) and after 14 days (animals which survived)
- Clinical observation: In each animal a number of clinical-toxicological signs were evaluated. Any change from the normal condition was noted and degree of severity of any clinical symptoms was assessed. The animals were examined at the following post-treatment intervals: 20 min, 1 h, 3 h, 24 h, 7 d, 14 d.
- Necropsy of the survivors performed: yes
- Other examinations performed: necropsy on died animals
Statistics:
Method of determining LD 50: according to Litchfield & Wilcoxon in combination with Gauß Integral

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
7.45 mL/kg bw
95% CL:
6.48 - 8.57
Remarks on result:
other: based on product; after 14 d
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 335 mg/kg bw
95% CL:
1 944 - 2 571
Remarks on result:
other: based on a.i.; after 14 d
Sex:
male/female
Dose descriptor:
LD50
Effect level:
8.1 mL/kg bw
95% CL:
6.82 - 9.64
Remarks on result:
other: based on product; after 24 h
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 430 mg/kg bw
95% CL:
2 046 - 2 892
Remarks on result:
other: based on a.i.; after 24 h
Mortality:
Number of deaths at each dose:
- 5 ml/kg bw: 2/10 (1 animal died within 24 h, 1 animal died within 48 h)
- 6.30 ml/kg bw: 2/10 (within 24 h)
- 7.94 ml/kg bw: 6/10 (5 animals died within 24 h, 1 animal died within 48 h)
- 10 ml/kg bw: 8/10 (7 animals died within 24 h, 1 animal died within 4 days)
Clinical signs:
>= 5 ml/kg bw: decreased motor activity, coordination disturbances, abnormal body posture, piloerection, diarrhoea, skin/mucosa cyanosis,
decreased body temperature with dose-dependant increase of effects. Clinical signs were observed at 20 minutes, 1 h and 3 h after application. Except of slight diarrhoea in one animal in dose groups 6.3, 7.94 and 10 ml/kg bw each, all symptoms were reversible after 24 hours. 7 days after application, all surviving animals were free of clinical symptoms.
>= 7.94 ml/kg bw: prone position
Body weight:
Weight gains were normal in all animals.
Gross pathology:
- Decedents: reddened gastric and intestinal mucosa
- Animals sacrificed at study termination 14 days p.a.: light reddened intestinal mucosa

Any other information on results incl. tables

LD50 values reported by the study authors refer to the test substance as specified above (30 % a.i.): 7.45 (6.48 - 8.57) ml/kg after 14 days and 8.10 (6.81 - 9.64) ml/kg after 24 hours
Density of the substance: roughly 1 g/cm3.
LD50 (14 day) referring to 100 % active substance: 2235 mg/kg bwLD50 (24 hours) referring to 100 % active substance: 2430 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
On the basis of the results obtained after a single oral administration, the oral LD50 was determined to be 7.45 ml/kg bodyweight based on product, corresponding to 2335 mg/kg bw active ingredient.
Executive summary:

In an acute oral toxicity study according to US Guideline Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, FDA, 1959, which is comparable to the OECD guideline 401 (1981), 5 male and 5 female Wistar rats were given a single oral dose of Coco AAPB (30 % a.i.) as delivered by the sponsor at doses of 5.0, 6.3, 7.94, and 10.0 ml/kg bw. Animals were then observed for 14 days.

At 5.0, 6.3, 7.94, and 10.0 ml/kg bw 2/10, 2/10, 6/10, and 8/10 animals died, respectively. Most animals died within 24 hours p.a.. Weight gains were normal in all animals. Clinical signs at >= 5 ml/kg bw were decreased motor activity, coordination disturbances, abnormal body posture, piloerection, diarrhoea, skin/mucosa cyanosis and decreased body temperature with dose response realtionship. At >= 7.94 ml/kg bw animals showed prone position. Clinical signs were observed at 20 minutes, 1 h and 3 h after application. Except of slight diarrhoea in one animal in dose groups 6.3, 7.94 and 10 ml/kg bw, each, all symptoms were reversible after 24 hours. 7 days after application, all surviving animals were free of clinical symptoms. Gross pathology examination of animals found dead revealed reddened gastric and intestinal mucosa. Animals sacrificed at study termination 14 days p.a. had light reddened intestinal mucosa.

Oral LD50Combined =  7.45 ml/kg bw after 14 d

Oral LD50Combined =  8.1 ml/kg bw after 24 h

LD50 determined refers to the test substance as delivered by the sponsor. There is no information on content of active ingredient of the test substance in the study report. However, according to producer information tested Coco AAPB has 30% active ingredient. The density is roughly 1 g/ml. Therefore the calculated oral LD50 combined referring to 100 % active substance = 2335 mg/kg bw after 14 d
Coco AAPB is of low toxicity based on the LD50 in males and females.