Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

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-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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.