Leach residues, cadmium cake

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliable with restriction. Not according to GLP or to specific test guidelines.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1988

Materials and methods

Principles of method if other than guideline:

A study has been conducted to determine the acute toxicity of the test material to mice. Groups of 20 mice were administered CdCl2 at doses of 0, 5, 35, 70, 140, 270, 530, and 790 µmol Cd/kg bw as a single dose by gavage. The animals were then observed for mortality and clinical soigns for 10 d and thereafter sacrificed. Additionally, histological examination of the major organs was done post necropsy.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cadmium chloride

EC Number:

233-296-7

EC Name:

Cadmium chloride

Cas Number:

10108-64-2

IUPAC Name:

cadmium dichloride

Details on test material:

- Name of test material (as cited in study report): CdCl2
- Impurity/additive/etc.: No information

Test animals

Species:

mouse

Strain:

other: CBA/Bom

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. 7-8 wk 
- Housing: Standard type III cages with beechwood bedding
- Diet (e.g. ad libitum): Rostock Mixture (KFK , Viby, Denmark), ad libitum
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 1
- Photoperiod (hrs dark / hrs light): 12h/12h with 0.5 h twilight

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

none

Doses:

0, 5, 35, 70, 140, 270, 530 and 790 µmol Cd/kg bw
Doses per time period: single dose

No. of animals per sex per dose:

20

Control animals:

yes

Details on study design:

- Post dose observation period: 10 d
- Necropsy of survivors performed: yes, on Day 10
- Other examinations performed:
Histopathology - Animals dying due to the acute toxicity of CdCl2 were also investigated histologically.
Other - Whole-body gamma counting was also performed on the test animals.

Statistics:

No statistics reported

Results and discussion

Effect levels

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 60.2 - < 89.9 mg/kg bw

Remarks on result:

other: Effects: irritation gastrointestinal epithelium, damage to liver and kidney, testicular necrosis

Mortality:

MORTALITY: 
Mortality increased with increasing doses.
Number of deaths at each dose level: 0/16, 0/8, 0/7, 0/10, 2/54, 11/60 and 36/42 for the doses of 0, 5, 35, 70, 140, 270, 530 and 790 µmol/kg bw respectively.

Clinical signs:

No information

Body weight:

No information

Gross pathology:

No Information

Other findings:

- Histopathology: Damage to intestinal tissues was most pronounced in the proximal parts of the intestinal tract.
- Potential target organs: Gastro-intestinal tract, liver, kidneys and testes
- Other observations: Whole body gamma-counting showed a dose dependent  delay of the faecal excretion of non-absorbed cadmium (109CdCl2). This effect was attributed to decreased peristaltis and at higher doses intestinal atony due to cadmium toxicity.

Any other information on results incl. tables

Tissue damage in gastric and intestinal epithelium, liver kidney and testes was graded from 0 (no apparent damage) to 3 by a pathologist. Average
score for the group was then calculated and a weighted score was determined by use of a table reported below.

Criteria used for assessment of cadmium-induced tissue damage from histological scores

Average score in individual tissues		Weighted score
Liver Kidney Stomach ≤1.0 ≥ 1.0  ≥ 2.0  ≥2.5	Testes Duodenum Ileum Colon ≤ 0.5 ≥ 0.5 ≥ 1.5  ≥2.5	- + ++ +++

A dose-related increase in tissue damage was observed both in the gastro-intestinal tract and in liver, kidney and testes:

Cd dose (µmol/kg) N animals	0 8	270 9	530 20	790 4
Liver Kidney Testes Stomach Duodenum Small intestine Large intestine	- - - - - - -	+ - - + + - -	+ - ++ + + + -	+ + +++ +++ ++ + -

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

A single oral dose of CdCl2 induced gastro-enteritis; subsequent hepatic and renal lesions were also observed. A dose-related increase in tissue
damage was observed both in gastro-intestinal tract, liver, kidneys and testes. The delayed faecal elimination also reported in this study may
significantly contribute to the development of both local and systemic toxicity in oral cadmium intoxication. The LD50 of the test material was estimated to be between 530 - 790 µmol (60.2 89.9 mg) Cd/kg bw.

Executive summary:

A study was conducted to determine the acute toxicity of the test material to mice. No GLP or test guideline was reported.

Groups of 20 mice were administered CdCl₂ at doses of 0, 5, 35, 70, 140, 270, 530, and 790 µmol Cd/kg bw (corresponding to 0, 0.6, 3.9, 7.9, 15.9, 30.7, 60.2, and 89.9 mg Cd/kg bw), as a single dose by gavage. The animals were observed for mortality and clinical signs for 10 d and thereafter sacrificed. Histological examination of the major organs was done post necropsy.

A dose-effect relation for tissue damage occurring among the surviving mice at 10 d after exposure was observed. Major effects were seen in the proximal parts of the intestinal tract. Catarrhal gastro-enteritis with hyperaemia, haemorrhagic gastro-enteritis with epithelial desquamation, or even necrosis of the entire epithelium with severe haemorrhage were observed in the stomach, duodenum, and although less severe, in the small intestine. Damage to liver and kidneys was only slight but extensive testicular necrosis was found at the highest dose. The LD50 of the test material was estimated to be between 530 - 790 µmol (60.2 - 89.9 mg) Cd/kg bw.