Organophosphates reproductive toxicity

Sikka, S.C., Gurbuz, N. (2006). Reproductive toxicity of organophosphate and carbamate pesticides. In Toxicology of Organophosphate and Carbamate Compounds (R.C. Gupta, ed.), pp. 447-62. Elsevier Academic Press, New York. 

Agent GA (Tabun). RfDe = 4 x 10 mg kg d" . A NOAEL was identified in a 90-d study in rats. A total uncertainty factor of 3000 was applied to account for protection of sensitive subpopulations (10), animal-to-human extrapolation (10), extrapolation from a subchronic to chronic exposure (3), and incomplete data base (3). An uncertainty factor of 3 was used to extrapolate from a subchronic to chronic exposure because of the unlikelihood that the LOAEL would have been substantially lower if the exposure had been chronic. A LOAEL-to-NOAEL uncertainty factor was not needed because a NOAEL was used in the derivation. The data base for GA lacks a multigeneration reproductive toxicity study, but because the available evidence indicates that organophosphate cholinesterase inhibitors such as GA are not likely to be reproductive toxins, the missing study was not considered critical. Therefore, a UFd of 3, not the default value of 10, was applied. A Modifying Factor of 3 was applied because the key study involved a nonoral exposure route (intraperitoneal injections). 

Most recent research continues to point to the immediate toxicity of these chemicals, the presence of their metabolites in the urine of the general population (especially children), and their potential long-term impact on reproduction. More generally, the potential neural damage organophosphates may cause. 

Tri-o-cresyl phosphate, not classified as a pesticide, is the only organophosphate for which testing and a final report were to have been completed in 1986. One of the TOCP studies under the auspices of CDC/NIOSH, and with an A completion priority, was a reproductive/developmental toxicity study. However, it is unclear from the TOCP listings (ref. 172a, Table 23) whether either the reproductive study or one of the neurologic/behavioral studies for TOCP was completed and reported in 1986. 

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