Lead 2,4,6-trinitro-m-phenylene dioxide

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

other: Communication regarding IQ

Adequacy of study:

supporting study

Data source

Reference

Reference Type:

publication

Title:

What is the meaning of non-linear dose-response relationships between blood lead concentrations and IQ?

Author:

Bowers TS & Beck BD

Year:

2006

Bibliographic source:

NeuroToxicology. 27(4): 520-524

Materials and methods

Type of study / information:

This communication addresses the purported existence of a supra-linear dose-response relationship between environmental measures such as blood lead concentrations and IQ. It explores the mathematical requirements placed on such dose-response relationships when the environmental measure, or independent variable, is lognormally distributed and the effect, or dependent variable, is normally distributed.

Endpoint addressed:

neurotoxicity

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Communication regarding mathematical dose-response relationships

Test material

Test material information

Constituent 1

Reference substance name:

Lead

EC Number:

231-100-4

EC Name:

Lead

Cas Number:

7439-92-1

Method

Ethical approval:

not applicable

Results and discussion

Results:

While recent literature has suggested the existence of a supra-linear dose-response relationship between blood lead concentration and IQ, the authors found no convincing evidence from animal studies supporting this relationship. Blood lead concentrations in the general population are lognormally distributed, whereas raw scores from various IQ tests are standardized to a normal distribution. The authors demonstrate that a supra-linear slope is a required outcome of correlations between data distributions where one is lognormally distributed and the other is normally distributed. The required supra-linear nature of the IQ-blood lead relationship will not necessarily change when confounders are included in the analysis if the confounders themselves are also normally distributed.

Applicant's summary and conclusion

Conclusions:

The authors conclude, "The analysis shows that caution should be taken in assigning biological significance to supra-linear dose-response relationships in these instances. Detailed analyses of such data sets should be conducted to determine if the magnitude of supra-linear slopes are more or less than mathematically required, and from there to consider biological significance."

Executive summary:

This communication addresses recent literature that purports the existence of a supra-linear dose-response relationship between environmental measures such as blood lead concentrations and IQ. The authors found no convincing evidence from animal studies supporting this relationship. Blood lead concentrations in the general population are lognormally distributed, whereas raw scores from various IQ tests are standardized to a normal distribution. The authors demonstrate that a supra-linear slope is a required outcome of correlations between data distributions where one is lognormally distributed and the other is normally distributed. The required supra-linear nature of the IQ-blood lead relationship will not necessarily change when confounders are included in the analysis if the confounders themselves are also normally distributed. The authors conclude, "The analysis shows that caution should be taken in assigning biological significance to supra-linear dose-response relationships in these instances. Detailed analyses of such data sets should be conducted to determine if the magnitude of supra-linear slopes are more or less than mathematically required, and from there to consider biological significance."