Amaryllidaceae, Allium Cepa L. (fresh bulb), Rutaceae, Citrus Limon (L.) Burm. F. (fresh pulp), extract, sodium chloride

Endpoint summary

Description of key information

A weight of evidence approch was used on to assess the acute toxicity of the UVCB substance " Amaryllidaceae, Allium Cepa L. (fresh bulb), Rutaceae, Citrus Limon (L.) Burm. F. (fresh pulp), extract, sodium chloride".

A bibliographic search was performed on the constituents composing this substance:

-Sodium Chloride 231-598-3, 40 -50%; oral EC 50 (rat) = 3000 mg/kg

-Monosaccharides (mainly glucose EC 200-075-1 and fructose EC 200-333-3) 25 -30%

Glucose, oral EC 50 (rat) = 25,800 mg/kg

Fructose, oral EC 50 (rat) = 4000 mg/kg

-Disaccharides (mainly saccharose EC 200-334-9) 10 -20%

Saccharose, oral EC 50 (rat) = 29,700 mg/kg

-Citric acid EC 201-069-1 , approx 1,5%; oral EC 50 (rat) = 11700 mg/kg

 

As a precautionary principle, the LD50 of the substance should be based on the LD50 of NaCl which is the lowest one:
LD50 Rat oral 3000 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

This endpoint study record is part of a Weight of Evidence approach comprising data of the constituents composing the UVCB substance "Amaryllidaceae, Allium Cepa L. (fresh bulb), Rutaceae, Citrus Limon (L.) Burm. F. (fresh pulp), extract, sodium chloride" constituents.

Qualifier:

no guideline followed

Principles of method if other than guideline:

this is a published data, from a peer reviewed data handbook.
However, no guideline is mentionned in the summary.

GLP compliance:

not specified

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 3 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Executive summary:

A weight of evidence approch was used on to assess the acute toxicity of the UVCB substance "Amaryllidaceae, Allium Cepa L. (fresh bulb), Rutaceae, Citrus Limon (L.) Burm. F. (fresh pulp), extract, sodium chloride".

A bibliographic search was performed on the constituents composing this substance:

-Sodium Chloride 231-598-3, 40 -50%; oral EC 50 (rat) = 3000 mg/kg

-Monosaccharides (mainly glucose EC 200-075-1 and fructose EC 200-333-3) 25 -30%

Glucose, oral EC 50 (rat) =25,800 mg/kg

Fructose,oral EC 50 (rat) =4000 mg/kg

-Disaccharides (mainly saccharose EC 200-334-9) 10 -20%

Saccharose,oral EC 50 (rat) =29,700 mg/kg

-Citric acid EC 201-069-1 , approx 1,5%; oral EC 50 (rat) = 11700mg/kg

 

As a precautionary principle, the LD50 of the substance should be based on the LD50 of NaCl which is the lowest one:
LD50 Rat oral 3000 mg/kg

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1971

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline, using males only. It was not compliant with GLP.

Justification for type of information:

This endpoint study record is part of a Weight of Evidence approach comprising data of the constituents composing the UVCB substance "Amaryllidaceae, Allium Cepa L. (fresh bulb), Rutaceae, Citrus Limon (L.) Burm. F. (fresh pulp), extract, sodium chloride" constituents.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

The observation period was 7 days instead of the recommended 14 in the current guideline.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

other: rat (ICR-JCL) and mice (SD-JCL)

Strain:

not specified

Sex:

male

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Doses:

5790 or 7000 mg/kg (mice)
12500 or 1800 mg/kg (rats)

No. of animals per sex per dose:

6 males

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Remarks:

on mice

Effect level:

ca. 5 790 mg/kg bw

Based on:

test mat.

Key result

Sex:

male

Dose descriptor:

LD50

Remarks:

on rats

Effect level:

ca. 11 700 mg/kg bw

Based on:

test mat.

Other findings:

Several minutes after administration, the spontaneous movement of mice and rats within the cage was observed to be activated. Fifty minutes thereafter they showed motor ataxia, and then laid down on their side. Mydriasis and decrease in rate of respiration and heart beat were observed. Death of all animals occurred within 20 to 180 minutes by respiratory failure. The animals which survived from the respiratory failure began to recover gradually within several hours and showed no toxic signs 24 hours later. No abnormalities were found in the necropsy except the presence of the haemorrage of the gastric mucosa.

Interpretation of results:

GHS criteria not met

Conclusions:

Acute oral LD50 values of 5790 in mice and 11700 in rats (males only) were determined in a reliable study conducted according to an appropriate test protocol. The exact method of administration of test substance was not specified in the publication. The study was not conducted according to GLP.

Executive summary:

A weight of evidence approch was used on to assess the acute toxicity of the UVCB substance "Amaryllidaceae, Allium Cepa L. (fresh bulb), Rutaceae, Citrus Limon (L.) Burm. F. (fresh pulp), extract, sodium chloride".

A bibliographic search was performed on the constituents composing this substance:

-Sodium Chloride 231-598-3, 40 -50%; oral EC 50 (rat) =3000 mg/kg

-Monosaccharides (mainly glucose EC 200-075-1 and fructose EC 200-333-3) 25 -30%

Glucose, oral EC 50 (rat) =25,800 mg/kg

Fructose,oral EC 50 (rat) = 4000 mg/kg

-Disaccharides (mainly saccharose EC 200-334-9) 10 -20%

Saccharose,oral EC 50 (rat) =29,700 mg/kg

-Citric acid EC 201-069-1 , approx 1,5%; oral EC 50 (rat) = 11700mg/kg

 

As a precautionary principle, the LD50 of the substance should be based on the LD50 of NaCl which is the lowest one:
LD50 Rat oral 3000 mg/kg

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

This endpoint study record is part of a Weight of Evidence approach comprising data of the constituents composing the UVCB substance "Amaryllidaceae, Allium Cepa L. (fresh bulb), Rutaceae, Citrus Limon (L.) Burm. F. (fresh pulp), extract, sodium chloride" constituents.

Qualifier:

no guideline followed

Principles of method if other than guideline:

this is a published data, from a peer reviewed data handbook.
However, no guideline is mentionned in the summary.

GLP compliance:

not specified

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 4 000 mg/kg bw

Based on:

test mat.

Clinical signs:

other: Kidney, Ureter, and Bladder: Other changes in urine composition

Interpretation of results:

GHS criteria not met

Executive summary:

A weight of evidence approch was used on to assess the acute toxicity of the UVCB substance "Amaryllidaceae, Allium Cepa L. (fresh bulb), Rutaceae, Citrus Limon (L.) Burm. F. (fresh pulp), extract, sodium chloride".

A bibliographic search was performed on the constituents composing this substance:

-Sodium Chloride 231-598-3, 40 -50%; oral EC 50 (rat) =3000 mg/kg

-Monosaccharides (mainly glucose EC 200-075-1 and fructose EC 200-333-3) 25 -30%

Glucose, oral EC 50 (rat) =25,800 mg/kg

Fructose, oral EC 50 (rat) =4000 mg/kg

-Disaccharides (mainly saccharose EC 200-334-9) 10 -20%

Saccharose,oral EC 50 (rat) =29,700 mg/kg

-Citric acid EC 201-069-1 , approx 1,5%; oral EC 50 (rat) = 11700mg/kg

 

As a precautionary principle, the LD50 of the substance should be based on the LD50 of NaCl which is the lowest one:
LD50 Rat oral 3000 mg/kg

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

This endpoint study record is part of a Weight of Evidence approach comprising data of the constituents composing the UVCB substance "Amaryllidaceae, Allium Cepa L. (fresh bulb), Rutaceae, Citrus Limon (L.) Burm. F. (fresh pulp), extract, sodium chloride" constituents.

Qualifier:

no guideline followed

Principles of method if other than guideline:

this is a published data, from a peer reviewed data handbook.
However, no guideline is mentionned in the summary.

GLP compliance:

not specified

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 25 800 mg/kg bw

Based on:

test mat.

Clinical signs:

other: Behavioral - coma Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - hypermotility, diarrhea

Interpretation of results:

GHS criteria not met

Executive summary:

A weight of evidence approch was used on to assess the acute toxicity of the UVCB substance "Amaryllidaceae, Allium Cepa L. (fresh bulb), Rutaceae, Citrus Limon (L.) Burm. F. (fresh pulp), extract, sodium chloride".

A bibliographic search was performed on the constituents composing this substance:

-Sodium Chloride 231-598-3, 40 -50%; oral EC 50 (rat) =3000 mg/kg

-Monosaccharides (mainly glucose EC 200-075-1 and fructose EC 200-333-3) 25 -30%

Glucose, oral EC 50 (rat) =25,800 mg/kg

Fructose,oral EC 50 (rat) = 4000 mg/kg

-Disaccharides (mainly saccharose EC 200-334-9) 10 -20%

Saccharose,oral EC 50 (rat) =29,700 mg/kg

-Citric acid EC 201-069-1 , approx 1,5%; oral EC 50 (rat) = 11700mg/kg

 

As a precautionary principle, the LD50 of the substance should be based on the LD50 of NaCl which is the lowest one:
LD50 Rat oral 3000 mg/kg

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1965

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication report which meets basic scientific principles.

Justification for type of information:

This endpoint study record is part of a Weight of Evidence approach comprising data of the constituents composing the UVCB substance "Amaryllidaceae, Allium Cepa L. (fresh bulb), Rutaceae, Citrus Limon (L.) Burm. F. (fresh pulp), extract, sodium chloride" constituents.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Wistar rats were exposed to high dosages of sucrose ranging from 5000 - 80 000 mg/kg bw in a single application via gavage to calculate the LD50 value. Clinical signs and pathological findings were correlated to the time point of death of nonsurviving animals after gavage. The reversibility of treatment-related effects was established in surviving animals 2 and 4 weeks after substance administration.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Department of Pharmacology, Queen´s University, Kingston, Ontario, Canada
- Age at study initiation: adult
- Weight at study initiation: 300-500 g (males), 250 - 300 g (females)
- Fasting period before study: Animals were fasted 16 h prior to administration (only food starvation, water was provided ad libitum).
- Housing: individual in metabolism cages
- Diet: Purina Fox Chow Checkers, Ralston Purina Company, St. Louis, Missouri, ad libitum
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 60 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 60 mL/kg bw

Doses:

5000 - 80 000 mg/kg bw (divided in 19 dosages), not further specified

No. of animals per sex per dose:

males: 48 (controls), 16 - 20 (mid-dose groups), 4 - 8 (the lowest 4 and highest 3 dose groups)
females: 30 (not further specified)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days and 1 month
- Frequency of observations and weighing: animals were observed 6 days a week for 2 weeks followed by casual observations up to 1 month
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, gross and histopathology, other: food and water intake, colonic temperature, determination of water levels in the organs, urinalyses.
To determine the above mentioned parameter, the following organs were examined: adrenal glands, brain, gastrontestinal tract including cardiac and pyloric stomach, small bowel, caecum and the colon, heart, kidneys, liver, lungs, muscle of the abdominal wall, skin, spleen, testes and the thymus gland in addition to the residual caracsses.

Statistics:

Statistical methods used were those described by Croxton (1953, Elementary Statistics with Applications in Medicine. Prentice-Hall, New York).

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 29 700 mg/kg bw

Based on:

test mat.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 35 400 mg/kg bw

Based on:

test mat.

Mortality:

In the lower dose groups ranging from 5 000 - 24 000 mg/kg bw, no deaths occured whereas all animals died from the high-dose groups (60 000, 70 000 and 80 000 mg/kg bw). The frequency distribution of deaths versus time of animals exposed to up to 50 000 mg/kg bw showed a peak at 4 h, a valley at 9 h and a broad plateau at 12 - 48 h. In detail, 76 deaths occured at 9 h or less, all except 1 animal given 35 000 mg/kg bw and more. 43 deaths occured beyond 9 h with 23 of them in animals given less than 35 000 mg/kg bw. 38 deaths occured within 10 - 48 h and 5 deaths within 2 - 11 days. In addition, 2 control animals died on the 5th day possibly due to the toxic effects of distilled water.

Clinical signs:

other: In general, dehydration of test animals was observed following administration. Further, initial clinical signs including hypokinesia, prostration, abdominal bloating and diarrhea were observed in test and control animals with controls showing the symptoms

Gross pathology:

In parallel to the generalized dehydration and loss of body weight, the following findings were detected in nonsurviving animals: severe but temporary gastroenteritis, a temporary mild hepatitis, marked nephritis and encephalities, focal necrosis of the heart, moderate stressor reactions in the adrenal and thymus gland, inhibition of spermatogenesis and arteriolitis. In contrast, the parenchyma of the lungs, pancreas, salivary glands, spleen and the skin appeared normal.
Organs of surviving animals appeared grossly normal.

REVERSIBILITY OF EFFECTS

The analyses indicated that the above mentioned clinical signs observed in nonsurviving animals were reversible in animals which survived the study. Clinical signs like hypokinesia, prostration, cyanosis, abdominal bloating, diarrhea, anorexia, glycosuria and weight loss disappeared by the 3rd day while polydispia and polyuria, the elevated body temperature and alkalinuria disappeared by the 6th day.

Potential target organs: brain and meninges, gastrointestinal tract, liver (seems to be capable to recover rapidly within 24 h in regard to histopathological findings)

Interpretation of results:

GHS criteria not met

Executive summary:

A weight of evidence approch was used on to assess the acute toxicity of the UVCB substance "Amaryllidaceae, Allium Cepa L. (fresh bulb), Rutaceae, Citrus Limon (L.) Burm. F. (fresh pulp), extract, sodium chloride".

A bibliographic search was performed on the constituents composing this substance:

-Sodium Chloride 231-598-3, 40 -50%; oral EC 50 (rat) =3000 mg/kg

-Monosaccharides (mainly glucose EC 200-075-1 and fructose EC 200-333-3) 25 -30%

Glucose, oral EC 50 (rat) =25,800 mg/kg

Fructose,oral EC 50 (rat) = 4000 mg/kg

-Disaccharides (mainly saccharose EC 200-334-9) 10 -20%

Saccharose,oral EC 50 (rat) =29,700 mg/kg

-Citric acid EC 201-069-1 , approx 1,5%; oral EC 50 (rat) = 11700mg/kg

 

As a precautionary principle, the LD50 of the substance should be based on the LD50 of NaCl which is the lowest one:
LD50 Rat oral 3000 mg/kg

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 000 mg/kg bw