Altered Sex Ratio
Fluorinated and Fluoride Pesticides

Can Med Assoc J, Jan 1, 1997; 156 (1): 37-41
Declining sex ratios in Canada
by Allan BB, Brant R, Seidel JE, Jarrell JF

Objective: To examine the trends in the proportion of annual live births that were male in Canada and to compare the trends with those in the United States,
Design: Analysis of census data.
Setting: Canada as a whole and 4 main regions (West, Ontario, Quebec and Atlantic)
Subjects: All live births from 1930 to 1990
Outcome measures: Sex ratio (expressed as the proportion of total live births that were male (male population) overall and by region
Results: The male proportion in Canada decreased significantly after 1970 (p <0.001); this represented a cumulative loss of 2.2 male births per 1000 live brths from 1970 to 1990. Although a decrease was observed in all four regions studied, only that in the Atlantic region was significant (p <0.001), representing a cumulatve loss of 5.6 male births per 1000 live births from 1970 to 1990. A significant decrease in the male proportion was also observed in the United States from 1970 to 1990 (p <0.001), although to a lesser degree than that observed in Canada, and represented a cumulative loss of 1.0 male births per 1000 live births.
Conclusions: The decreased sex ratio in Canada adds to the growing debate over changes in biological markers and their potential causes. In addition, the study illustrates the potential use of the sex ratio as a widely available, unambiguous measure of the reproductive health of large populations.

The use of high doses increases the likelihood that potentially significant toxic effects will be identified. Findings of adverse effects in any one species do not necessarily indicate such effects might be generated in humans. From a conservative risk assessment perspective however, adverse findings in animal species are assumed to represent potential effects in humans, unless convincing evidence of species specificity is available.

-- Food and Agricultural Organization of the United Nations

Note: This is not an exhaustive list.
When time allows more information will be added.

Fipronil - Acaricide, Insecticide - CAS No. 120068-37-3

Abstract: Copepods are the most abundant arthropods on earth and are often the most important secondary producers in estuarine/marine food webs. The new GABA (gamma-aminobutyric acid)-disrupting insecticide fipronil (FP) induces unique sex-specific reproductive dysfunction in male meiobenthic copepods, leading to trans-generational population depression at environmentally realistic concentrations (0.63 microg/L). Using a newly developed 96-well microplate lifecycle bioassay, more than 700 individual Stage-I juveniles were reared to adulthood in as short as 12 days in only 200 microL of control (CTL) or 0.63 microg-FP/L seawater solution. Individual virgin male: female pairs were then cross-mated for all possible combinations within and across rearing treatments and allowed to mate for an additional 12 days in CTL or 0.63 microg-FP/L solution. FP at 0.63 microg/L caused no significant lethality to any mating combinations but evoked 73% or 89% inhibition of reproduction when FP-reared males were mated with either a control- or FP-reared female in FP solution, respectively. In contrast, when CTL-reared males were mated with FP-reared females in FP solution, there was no difference in reproductive success compared to FP-free controls. When FP-reared males were mated with either female group in FP-free solution, these mating pairs displayed a 3-day delay in time to brood sac extrusion but ultimately did reproduce. As fipronil (1) has a high K(ow), (2) is persistent in sediments where meiobenthic copepods live, and (3) has been detected in estuarine waters >0.7 microg/L, it may pose high risk to copepod production in estuarine systems.
Ref: Environ Sci Technol. 2004 Jan 15;38(2):522-8. Phenylpyrazole insecticide fipronil induces male infertility in the estuarine meiobenthic crustacean Amphiascus tenuiremis; by Cary TL, Chandler GT, Volz DC, Walse SS, Ferry JL.

Flonicamid - Insecticide - CAS No. 158062-67-0

-- TERATOLOGY, RABBIT Rangefinding Study: 52964 - 0060 216034 “IKI-220 Technical: A Teratogenicity Study in Rabbits Preliminary Study,” (Takahashi, K.; Institute of Environmental Toxicology, Ibaraki, Japan; Laboratory Study #: IET 000024; 2/21/02). Flonicamid technical (98.7% pure) was administered via oral gavage to artificially inseminated SPF Japanese White rabbits (Kbl:JW) (6/dose) at 0 (1% sodium carboxymethyl cellu- lose), 3, 10 and 30 mg/kg/day during gestation days 6 through 27. Maternal NOEL = 10 mg/kg/day (There were slight effects on body weight, body weight gain, clinical signs, abortion (2/6 does at 30 mg/kg), food consumption, gravid uterine weights and placental weights at 30 mg/kg/day.) Developmental NOEL = 10 mg/kg/day (There were lowered sex ratios, and fewer implants and live fetuses at 30 mg/kg/day.) There were no major deficiencies in this study. It was for the purpose of dose rangefinding for the definitive study. No adverse effect indicated. These data are supplemental. Silva, 2/10/05 Definitive Study:
Reference: April 28, 2005 - Summary of toxicology data. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.

TFM (3-Trifluoro-Methyl-4-Nitro-Phenol) - Lampricide, Piscicide - CAS No. 88-30-2

Note from FAN: The use of TFM in the Great Lakes began at the end of the 1950's. The chief outlet of the Great Lakes is the St. Lawrence River, which flows northeast from Lake Ontario to the Gulf of St. Lawrence on the North Atlantic Ocean. Since the introduction of TFM in the Great Lakes there has been a dramatic and significant shift from male to female sea lampreys. A confounding factor may be that TFM was found to be contaminated with dioxin in the early 1990s. It is unclear whether dioxin influenced this alteration, or TFM alone, or the combination of TFM and dioxin. Also it is unclear when the dioxin contamination of TFM began. If you know, please contact me and I will share the information. Thanks. EC. Sept. 2003.

-- TFM treatments have been associated with induction of hepatic mixed function oxyganase activity and altered levels of circulating steroids in fish and induced hepatic vitellogenesis in primary cultures of rainbow trout hepatocytes (Hewitt et al. 1997). As such, TFM acts as an estradiol agonist and has a demonstrated endocrine disrupting effect...
-- Abundance of sea lamprey peaked in several Great Lakes before chemical control began. The sex ratio in these peak populations were predominately males (68-71%). Following a decade of lampricide treatments, populations of sea lampreys showed marked declines and the sex ratios in these populations shifted toward a predominance of females accounting for 72% of the population (Henrich, et al, 1979). This publication by Henrich concludes that lampricides reduced the populations of sea lampreys in the Great Lakes and contributed to the sequential shifting of the sex composition from a predominance of males to a predominance of females. There are no data to support that the endocrine mediated effect associated with TFM is related to the observed sex-ratio shifts among TFM-treated populations of sea lamprey [page 23].
Ref: November 1999 US EPA's Reregistration Eligibility Decision (RED) for 3-Trifluoro-Methyl-4-Nitro-Phenol and Niclosamide).

Abstract: Growth and age at metamorphosis were determined for populations of larval sea lampreys that became reestablished after chemical treatments of tributaries of Lakes Superior and Michigan (USA) with the selected lampricide, 3-trifluoromethyl-4-nitrophenol. Age at metamorphosis varied from 3-7 yr. Growth of ammocetes varied considerably from stream to stream and within streams. Mean lengths of ammocetes of age group III in late summer or early fall in different streams ranged from 65-144 mm. Ammocetes of the 1st yr class established after a chemical treatment grew faster than those of succeeding year classes. Transformation at an early age usually occurred only among fast-growing larvae in large streams. A reversal of the sex ratio, from predominately male to predominately female, followed the reduction of the adult sea lamprey population. Sex ratios of larval and recently metamorphosed sea lampreys reestablished after chemical treatments rapidly shifted from an excess of males to an excess of females. The shift in sex ratio was related to decreased densities of sea lampreys resulting from treatments.
Ref: PURVIS HA (1979). Variations in growth, age at transformation, and sex ratio of sea lampreys (Petromyzon marinus) reestablished in chemically treated tributaries of the upper Great Lakes (USA). GREAT LAKES FISH COMM TECH REP; 0 (35). 1-36.

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