Debunking Human Health Risk, APPENDIX D - LBAMspray.com

LIGHT BROWN APPLE MOTH ERADICATION PROJECT
APPENDIX D
DRAFT PEIR
HUMAN HEALTH RISK ASSESSMENT
Notwithstanding the effects of chlorpyrifos that are distinct from its action on ChE, inhibition of
ChE continues to be used as a sensitive indicator of chlorpyrifos exposure. OEHHA (2008a) has
recently reviewed a series of toxicity studies that measured inhibition of red blood cell (RBC),
plasma, or brain ChE, and/or physical and cognitive impairment to assess chlorpyrifos-induced
developmental toxicity. Those studies reveal a pattern of treatment-related decreases in neonatal
weight, growth, or survival; inhibition of brain ChE; behavioral changes; and impaired learning
or memory loss. The lowest NOAEL was identified in rats by Maurissen et al. (2000) as 0.3
mg/kg, with the LOAEL in that study, 1 mg/kg, associated with impairment of brain ChE.
Chlorpyrifos exposure during gestation may result in behavioral changes that manifest long after
exposure has ended and ChE levels have recovered. Delayed-onset deficits in memory have been
observed in adolescent and adult rats exposed in utero, an effect that has been postulated to be
due to disruption of development of normal cholinergic activity (OEHHA 2008a).
D3.1.1.2.6 Teratogenicity
Chlorpyrifos, but not TCP, appears to be teratogenic when administered in sufficiently large
doses. Chlorpyrifos given as a single intraperitoneal injection (80 mg/kg) caused a significant
increased incidence of fetal mortality, fetal resorption, cleft palate, missing thoracic vertebrae,
and a decrease in caudal vertebrae when administered to mice on gestation day (GD) 10.
Significant maternal toxicity was not observed (Tian et al. 2005). Chlorpyrifos adversely affected
fetal weight and caused an increase in resorption and fetal death when provided to rats by gavage
at 25 mg/kg on GD 6-15. Doses of 5 or 15 mg/kg did not yield any evidence of teratogenicity.
Maternal toxicity occurred in the highest dose group as well, and may have caused or contributed
to the adverse effects seen in fetuses (Farag et al. 2003). An evaluation of TCP for its teratogenic
potential utilized doses of 0-150 mg/kg chlorpyrifos for rats (GD 6-15) and 0-250 mg/kg for
rabbits (GD 7-19). No effects occurred in either species on fetal weight, viability, or any type of
abnormality despite the induction of maternal toxicity in the higher dose groups (Hanley et al.
2000).
D3.1.1.2.7 Reproductive Toxicity
Epidemiological evidence suggests that exposures to chlorpyrifos may be related to increased
DNA damage in sperm as well as other reproductive effects. In a case-control study involving
men from Minnesota and Missouri, Swan et al. (2003) linked increased levels of TCP to
decreased sperm quality (Swan et al. 2003). A series of cross-sectional studies based on the same
study population also linked increased TCP metabolites in urine to increased DNA damage in the
sperm of the study population (Meeker 2004a, 2004b), lower reproductive hormone levels,
including testosterone and estradiol (Meeker 2006a, 2008), and higher thyroid stimulating
hormone (TSH) levels (Meeker 2006b).
In separate two-generation studies, chlorpyrifos administered as Dursban ® (to 1.2 mg/kg) or as
97.8% pure compound (to 5 mg/kg) did not affect indices of reproduction or fertility in male or
female rats despite the induction of significant RBC-, plasma-, and brain-ChE inhibition by the 5
mg/kg dose (OEHHA 2008a). Reduced pup weights and increased pup mortality observed at the
5 mg/kg dose in the study occurred only at a dose that caused parental toxicity and, thus, are not
considered reproductive effects. Substantially higher doses of chlorpyrifos (7.5, 12.5, and 17.5
mg/kg) administered to male rats by gavage for 30 days, resulted in a significant decrease in
testes weight, sperm counts, and in serum testosterone concentrations. These effects were
associated with degenerative changes in the seminiferous tubules. Histological examination of
D3-10 App D_HHRA_508.doc JULY 2009