Cadmium hydroxide

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not applicable

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliable with restriction. Well documented. Not according to GLP Method not in compliance with ER 67/548/EEC, Annex V and OECD 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:

Semichronic oral toxicity of cadmium 1. Studies on rats

Author:

Loeser E and Lorke D

Year:

1977

Bibliographic source:

Toxicology 7: 215-224

Materials and methods

Principles of method if other than guideline:

A study was conducted to determine the repeated dose oral toxicity of cadmium in rat. Clinical signs, bodyweight, food consumption, hematology were followed. Histology was conducted at study end.

GLP compliance:

no

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: CdCl2.1H2O, analytical grade (Merck A.G., Darmstadt)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann (Borchen/Paderborn)
- Age at study initiation: no information
- Weight at study initiation: 44-55g
- Housing: kept singly under standard conditions in Macrolon cages (type II)
- Diet: powdered altromin ad libitum
- Water: tap water ad libitum

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test material CdCl2.1H2O was mixed with powdered feed

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no information

Duration of treatment / exposure:

3 months

Frequency of treatment:

not relevant

Doses / concentrations

Remarks:

Doses / Concentrations:
1, 3, 10, 30 ppm
Basis:
nominal in diet

No. of animals per sex per dose:

20 animals per sex per dose

Control animals:

yes

Details on study design:

none

Positive control:

none

Examinations

Observations and examinations performed and frequency:

Determination of liver function, renal function, blood pressure and Cadmium contents in kidneys, liver, urine and faeces

Sacrifice and pathology:

histopathology

Other examinations:

none

Statistics:

Comparison of mean values of animal and organ weights: Wilcoxon test.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not examined

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

none

Effect levels

Dose descriptor:

NOAEL

Effect level:

3 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: no effects on any parameters followed but Cd accumulated dose-dependently in the kidneys and liver

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

- appearance, behaviour, food consumption, growth and mortality of treated rats of all groups were not affected

- no increased blood pressure

- no change in hemoglobin

- not found liver effects

- no effect on renal function

- pituitary, adrenals, thyroid, heart, brain, gonads, urinary bladder, uterus, spleen, stomach, intestines and thymus were unaffected

- no effect or only a small effect (10–20% decrease) on body weight

- no testicular histopathologic lesions

- no decrease in male reproductive success

- no adverse reproductive effects

 

Applicant's summary and conclusion

Conclusions:

This study determined the repeated dose oral toxicity of cadmium in rat giving a NOAEL of 30ppm (ca 3mg Cd/kg bw/d)

Executive summary:

Cadmium (in the form of CdCl2) was fed to groups of 20 male and 20 female rats each over a period of 3 months in concentrations of 0, 1, 3, 10 and 30 ppm. Appearance, behaviour, food consumption, growth and mortality of the treated rats of all groups were not affected during the 3-month period. The cadmium concentrations did not cause blood, liver or kidney damage. The systolic blood pressure of the treated animals was not increased. Autopsies and histopathological investigation of the animals showed no sign of any alterations. Cadmium accumulated dose-dependently in the kidneys and liver. Concentrations of cadmium up to 30 ppm in their feed were tolerated by rats over a period of 3 months without harm.