Endosulfan and Endocrine Disruption - A review of published literature

A review of published literature on the subject “Endosulfan and Endocrine Disruption: Human Risk Characterization” has been prepared for Makhteshim Agan of North America by Laura Plunkett, Ph.D., DABT, Integrative Biostrategies, LLC, Houston, Texas.

SUMMARY

In vitro studies:

In the literature reporting in vitro data, in all cases, the in vitro screening studies employ a method of exposure involving direct cell contact without consideration of metabolism. This exposure method is not directly relevant to human pharmacodynamics.

In almost all cases, the estrogenic effects elicited by Endosulfan were compared with the effects produced by a hormone “estradiol”. Though the studies indicate that Endosulfan exhibits weak estrogenic activity, the effects are seen at doses of Endosulfan much higher (105 – 106 times) than the doses of estradiol that would have produced similar effects. Such levels of Endosulfan are much higher than what might be encountered in the environment. Hence these levels are not relevant for risk assessment. Potency of Endosulfan is found to be very low compared to even natural phytoestrogens present in human diet.

In vivo studies:

None of the in vivo studies reported are based on design same or similar to that of Tier 1 or Tier 2 assays proposed by EPA.

As per the studies, high dose exposures to Endosulfan may be a risk for toxicity to male reproductive organs, these levels of exposure are not available in the environment.

The testicular effects in animals were associated with high doses of Endosulfan.

Binding potency of Endosulfan to estrogen receptors as determined ex vivo was found to be many orders of magnitude lower than the binding affinity of the natural hormone estradiol.

Effects in Humans:

Data on actual exposure is inferred, not directly measured. Therefore available data cannot be used for human health risk assessment in any scientifically defensible method.

Developmental toxicity studies:

In the developmental toxicity studies, Endosulfan treatment during the period of organogenesis of the developing fetus did not affect the development of the endocrine system.

In the case of studies reporting effects on steroidogenesis and hormone levels, the effects were also shown to be reversible.

Issue of synergism:

The results were not reproducible Hence synergy is not issue of concern.

CONCLUSION:

“After considering all available data, the weight-of-the-evidence indicates the Endosulfan is not an endocrine-disrupting compound at environmentally relevant concentrations.”