Cadmium

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985-1989 (baseline CadmiBel) 1991-1994 (follow-up PheeCad)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

All selected studies were evaluated with a check-list relating to population, exposure, endpoints, biases and confounders. Used check-list are established by Professor Philippe Hotz from the Institut für Sozial- und Präventivmedizin der Universität Zürich (EU RA 2008).

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:

Renal effects of low-level environmental cadmium exposure: 5-year follow-up of a subcohort from the Cadmibel study

Author:

Hotz P , Buchet J P, Bernard A , Lison D and Lauwerys R

Year:

1999

Bibliographic source:

The Lancet 354: 1508-1513

Materials and methods

Study type:

cross sectional study

Endpoint addressed:

repeated dose toxicity: oral

Principles of method if other than guideline:

Study was conducted to assess whether environmental exposure to cadmium is associated with renal dysfunction.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Cadmium

EC Number:

231-152-8

EC Name:

Cadmium

Cas Number:

7440-43-9

Molecular formula:

Cd

IUPAC Name:

cadmium

Details on test material:

none

Method

Type of population:

general

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

STUDY POPULATION:
E: 1699 (M/F), age : 20-about 80 y
residents from two areas with low and two areas with high exposure to cadmiumto give a sufficiently large range of cadmium body burden in the
study population and to match the socio-economic environment of each polluted area with that of at least one less polluted area.
2327 were asked to participate, final population: 1699

Exposure assessment:

measured

Details on exposure:

U-Cd; 24-hr. Urinary samples
Geometric mean: 0.84/24h

Statistical methods:

distributions were normalised by logarithmic transformation. Determinants affecting renal measurements were traced by stepwise regression.
Logistic model (relation between the frequency of abnormal values of the renal measurements and the internal dose of Cd assessed by its urinary excretion)

Results and discussion

Results:

-Association between tubular parameter and Cd-U : partial r² : 0.0684-0.0160
-After standardisation for several possible confounding factors, 5 variables (urinary excretion of beta-2µglobulin, RBP, NAG, amino-acids and calcium) were significantly associated with the urinary excretion of Cd (as a marker of Cd body burden), suggesting the presence of tubular dysfunction.
There was a 10% probability of values of these variables being abnormal when Cd excretion exceeded 2-4 µg/24h. Excretion reached this threshold
in 10% of non-smokers
-Dose - response curve : A positive association was found between Cd-U measured at baseline and the risk of fractures in women and possibly with a higher risk of height loss in men

Confounding factors:

Taken into account and tested in the model :
age, gender, renal disease, diabetes, medication, BMI, urinary tract disease

Strengths and weaknesses:

none

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:

After adjustment for age, gender, smoking, use of medications and urinary tract disease, it was found that tubular effects (increased Ca-U) occurred
in the general population at Cd-U levels ≥ 2 µg/24 h (roughly equivalent to 2 µg/g creatinine). “Elevated” (> 95th percentile in the same cohort after
exclusion of individuals with renal disease, analgesic abuse and diabetes) urinary excretion of Ca, NAG, RBP, ß2M and amino acids was predicted with a probability of 10 % when the urinary excretion of cadmium reached 1.9, 2.7, 2.9, 3.1 and 4.3 µg/24 h, respectively

Executive summary:

In a cross-sectional population study to assess whether environmental exposure to cadmium is associated with renal dysfunction, 1699 subjects aged 20-80 years were studied as a random sample of four areas of Belgium with varying degrees of cadmium pollution. After standardisation for several possible confounding factors, five variables (urinary excretion of retinol-binding protein, N-acetyl-beta-glucosaminidase, beta 2-microglobulin, aminoacids, and calcium) were significantly associated with the urinary excretion of cadmium (as a marker of cadmium body burden), suggesting the presence of tubular dysfunction. There was a 10% probability of values of these variables being abnormal when cadmium excretion exceeded 2-4 micrograms/24 h. Excretion reached this threshold in 10% of non-smokers. There was also evidence that diabetic patients may be more susceptible to the toxic effect of cadmium on the renal proximal tubule.