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Toxicity

There are no studies that have evaluated the acute toxicity of heptachlor following inhalation exposure; thus, acuteduration inhalation MRL was not derived.
A number of studies have evaluated the toxicity of heptachlor following acute oral exposure. The results of these studies suggest several sensitive targets of toxicity including the liver, nervous system, reproductive system, and the developing organism. The available data suggest that the most sensitive effect is impaired fertility observed in female rats administered heptachlor for 14 days prior to mating; this end point was considered a serious LOAEL and was not appropriate for derivation of an acuteduration oral MRL.
Although there are limited toxicokinetic and mechanistic data for heptachlor, it is likely that its toxicity is not routespecific. The identified target organs would likely be the same for oral, inhalation, and dermal exposure; however, it is notpossible to predict threshold concentrations.


The World Health Organization according to the LD50 values for rats has listed heptachlor in WHO Acute Hazard Rankings in class II moderately hazardous substance. Studies performed by the U.S. EPA placed heptachlor formulations in Acute Toxicity Rankings in a Category 1 and 2, “Moderately to Highly Toxic” (Table below).

Study TypeRouteSpeciesResultUnits
LCL0InhalationCat150.0mg/m3/4H
LD50DermalRat119.0mg/kg
LD50OralGuinea pig 116.0mg/kg
LD50OralHamster100.0mg/kg
LD50OralMouse68.0mg/kg
LD50OralRat40.0mg/kg

The targets of toxicity of heptachlor following intermediateduration oral exposure appear to be the same as those identified following acuteduration oral exposure and include the liver, nervous system, reproductive system, and the developing organism. Of these targets, the developing organism appears to be the most sensitive. The intermediateduration oral MRL for heptachlor was based on these developmental effects. The potential systemic toxicity of heptachlor has not been adequately assessed; although several studies have evaluated systemic end points, many of these studies were poorly reported or examined a limited number of end points No intermediateduration inhalation or dermal studies were identified.

There are no data on chronic oral exposures in humans.
There are occupational studies of workers engaged in the manufacture of heptachlor in which the exposures are presumed to be predominantly inhalation with contributions from the dermal route. No adverse health effects have been identified in these cohorts that could be positively associated with heptachlor exposure. There is a limited publicly available database on the chronic oral toxicity of heptachlor. A 2yea.r study submitted to EPA under Federal Insecticide, Fungicide, and Rodenticide Act identified the liver as a critical target of toxicity. This finding is consistent with the available intermediateduration studies.

Although a couple of studies have attempted to establish an association between heptachlor derivative blood levels and premature delivery or stillbirth among women presumably exposed via ingestion, elevated levels of other compounds (particularly PCBs, lindane, and dieldrin) limit the interpretation of the results. Animal studies have found impaired fertility and pregnancy losses following oral exposure to heptachlor. The mechanism of the reproductive toxicity has not been elucidated; the available data suggest that both males and females may be affected.

Several studies have examined the potential developmental toxicity of heptachlor and its epoxide derivative. These studies examined potential effects in the children of women exposed to heptachlor and heptachlor epoxide in contaminated cows milk or examined the possible association between maternal heptachlor epoxide levels and developmental effects. Several animal studies have also examined developmental toxicity. The finding of impaired development of the nervous and immune systems was used as the basis of the intermediateduration oral MRL for heptachlor. This study did not identify a NOAEL for these effects. Impaired spatial memory was observed at the lowest dose tested among the offspring exposed until postnatal day 42, but not in rats exposed until postnatal day 21.

 


Structure formula of Heptachlor


3D structure of Heptachlor