Perinatal Exposure to Low Levels of the Environmental Antiandrogen Vinclozolin Alters Sex-Differentiated Social Play and Sexual Behaviors in the Rat

Classified as probably not a substantial claim. May combine two claims.

Males typically engage in more bouts of play and perform more behaviors during bouts than females.

“Males typically engage in more bouts of play and perform more behaviors during bouts than females (Thor and Holloway 1983).”

• cites Thor and Holloway 1983 sourcePartly supported

  The Results report that juvenile males solicited play more frequently than females, and the General Discussion describes greater play solicitation by males. Neither passage establishes that males had more bouts of play or performed more behaviors within each bout; the paper distinguishes solicitation from play fighting. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Antiandrogens are already recognized as one of the factors responsible for the recent increase of hypospadias.

“They are already recognized as one of the factors responsible for the recent increase of hypospadias, a male reproductive disorder where the urethral opening is on the ventral surface of the penis (Baskin et al. 2001; Davis et al. 1998; Egeland et al. 1994; Jensen et al. 1995; Sharpe and Skakkebaek 1993).”

• cites Baskin et al. 2001 sourcePartly supported

  The discussion (p. 1180) says environmental antiandrogens can disrupt male urogenital development and lead to hypospadias. But the paper describes environmental causes of the reported increase as a concern rather than an established explanation (p. 1177), and says a clear etiology has not been established. It does not support calling antiandrogens already recognized factors responsible for the recent increase. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Davis et al. 1998 sourceNot checked — no full text of the source
• cites Egeland et al. 1994 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Female guppies prefer males with high rates of sexual display, and Vz exposure reduces male guppy courtship display.

“For instance, female guppies prefer males with high rates of sexual display, and Vz exposure has been shown to significantly reduce male guppy courtship display (Baatrup and Junge 2001; Bayley et al. 2002).”

• cites Baatrup and Junge 2001 sourceSupported
• cites Bayley et al. 2002 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Other manipulations such as prenatal protein deprivation, perinatal genistein exposure, prenatal PCB exposure, or maternal stress during gestation can also demasculinize play behavior.

“Other manipulations such as prenatal protein deprivation (Almeida et al. 1996), perinatal genistein exposure (Flynn et al. 2000), prenatal polychlorinated biphenyl (PCB) exposure (Vreugdenhil et al. 2002), or maternal stress during gestation can also demasculinize play behavior (Ward and Stehm 1991).”

• cites Almeida et al. 1996 sourcePartly supported

  The Behavioral Measures section reports that prenatal protein malnutrition reduced pinning, a measure of juvenile social play, on test sessions 2 and 3. But it found no significant effect of sex or interaction involving sex, so the reduction does not establish that play behavior was specifically demasculinized. No page number is available in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Flynn et al. 2000 sourceNot checked — no full text of the source
• cites Vreugdenhil et al. 2002 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

In normal juvenile rats, play solicitation increases after longer periods of deprivation.

“In normal juvenile rats, play solicitation increases after longer periods of deprivation (Thor and Holloway 1983).”

• cites Thor and Holloway 1983 sourcePartly supported

  Experiment 3 reports that play solicitation increased with longer social-isolation intervals. However, the deprivation comparison tested only male juvenile rats exposed to scopolamine-treated, nonplayful males; it does not establish the same increase for juvenile rats generally or during normal reciprocal play. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Higher prenatal levels of PCBs are associated with less masculinized play behavior in Dutch schoolboys and more masculinized play in schoolgirls.

“higher prenatal levels of PCBs have been associated with less masculinized play behavior in Dutch schoolboys and more masculinized play in schoolgirls (Vreugdenhil et al. 2002).”

• cites Vreugdenhil et al. 2002 sourceSupported

May combine two claims.

There was a significant increase in seminal emissions, with the 12-mg/kg group expelling more often than any other group.

“Surprisingly, there was a significant increase in seminal emissions [F(4,40) = 7.37, p < 0.01; Figure 6] as the 12-mg/kg group expelled more often than did any of the other groups.”

May combine two claims.

There were no exposure-related changes in maternal body weight, pup body weight, or anogenital distance.

“nor were there any exposure-related changes in maternal body weight, pup body weight, or AGD (males, Table 2; females, Table 3).”

May combine two claims.

There was a significant exposure-related decline in total erections per session, with each Vz group producing significantly fewer erections than controls.

“We found a significant exposure-related decline in total erections per session [F(4,40) = 4.62, p < 0.01; Figure 4] as each of the Vz groups produced significantly fewer erections than controls.”

May combine two claims.

The latency to the first penile reflex and the frequency of E2 and E3 responses were not significantly different.

“The latency to the first penile reflex and the frequency of E2 and E3 responses were not significantly different.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Visual inspection of the data suggested a dose-related trend in nipple and areola retention in immature male offspring.

“Although we did not observe nipple and areola retention in immature male offspring, visual inspection of the data suggests that there was a dose-related trend.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The percentage of male pups with at least one visible areola on PND12 was not significantly different among exposure groups (p = 0.367).

“The percentage of male pups that possessed at least one visible areola on PND12 (control, 18%; 1.5 mg/kg, 50%; 3 mg/kg, 44%; 6 mg/kg, 45%; 12 mg/kg, 33%) was not significant (p = 0.367).”

May combine two claims.

There were no significant main effects of exposure, sex, or PND on total play behaviors, but there was a significant exposure × PND interaction.

“Although we found no significant main effects of the exposure, sex, or PND factors on total play behaviors, there was a significant exposure × PND interaction [F(1,21) = 7.72, p = 0.01].”

May combine two claims.

The behavior of Vz-exposed males resembled female offspring, who performed more play on PND34 than on PND22.

“The behavior of the exposed males actually resembled the female offspring, who performed more play on PND34 than on PND22.”

May combine two claims.

Procymidone and iprodione are structurally similar to Vz and produce a nearly identical profile of effects on the reproductive system.

“Procymidone and iprodione are fungicides that are structurally similar to Vz, and they produce a nearly identical profile of effects on the reproductive system (Gray et al. 1999b; Ostby et al. 1999).”

• cites Gray et al. 1999bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Ostby et al. 1999 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

During play, rats perform numerous crawl-over behaviors with same-sex partners.

“During play, rats perform numerous crawl-over behaviors with same-sex partners.”

May combine two claims.

Female rats can detect subtle behavioral deficits and prefer to copulate with healthy, dominant males.

“Female rats can detect subtle behavioral deficits and prefer to copulate with healthy, dominant males (McClintock et al. 1982).”

• cites McClintock et al. 1982 sourceNot checked — no full text of the source

May combine two claims.

Adult male rats exposed to perinatal Vz will mount sexually receptive females but are unable to achieve vaginal penetration, suggesting an underlying erectile dysfunction.

“Gray et al. (1994) have shown that adult male rats exposed to perinatal Vz will mount sexually receptive females but are unable to achieve vaginal penetration, suggesting that there is an underlying erectile dysfunction.”

• cites Gray et al. (1994) sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

There is a shift of interest in male pups in their preferred play partners during PND36-40 from male to female.

“There is a shift of interest in male pups in their preferred play partners during the postnatal day (PND)36–40 period, from male to female (Meaney and Stewart 1981).”

• cites Meaney and Stewart 1981 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

One study using chronic low-level dietary exposure to Vz found that female rats were more sensitive than males.

“One study that used a chronic, low-level dietary exposure to Vz found that female rats were more sensitive than males (Flynn et al. 2001).”

• cites Flynn et al. 2001 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Female play can also be altered by neuro-endocrine manipulations.

“although it is well known that female play can also be altered by neuro-endocrine manipulations (Hines 2003; Nordenstrom et al. 2002; Servin et al. 2003).”

• cites Hines 2003 sourceNot checked — no full text of the source
• cites Nordenstrom et al. 2002 sourceNot checked — no full text of the source
• cites Servin et al. 2003 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Older, sexually mature but naive males will perform crawl-overs with females until they achieve a mount with a successful vaginal intromission.

“Older, sexually mature but naive males will perform crawl-overs with females until they achieve a mount with a successful vaginal intromission.”

May combine two claims.

Although reductions in rat reproductive organ weights demonstrate that environmental antiandrogens can produce long-term effects after perinatal exposure, they do not necessarily represent the most sensitive end points.

“Thus, although effects such as reductions in rat reproductive organ weights demonstrate that environmental antiandrogens can produce long-term effects after perinatal exposure, they do not necessarily represent the most sensitive end points.”

May combine two claims.

Juvenile play is a sexually dimorphic behavior that is an important precursor to adult sexual behavior and dominance relationships.

“Juvenile play is a sexually dimorphic behavior that is an important precursor to adult sexual behavior (Pellis et al. 1992) and dominance relationships (Pellis and Pellis 1992).”

• cites Pellis et al. 1992 sourceNot checked — no full text of the source
• cites Pellis and Pellis 1992 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Early environmental factors can affect important neonatal or juvenile social interactions, culminating in aberrant behaviors in adulthood.

“Thus, early environmental factors can affect important neonatal or juvenile social interactions, culminating in aberrant behaviors in adulthood (Dunlap et al. 1978).”

• cites Dunlap et al. 1978 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

After the first intromission, mounting behavior increases and crawl-overs decrease.

“After the first intromission, mounting behavior increases and crawl-overs decrease.”

Probably not a substantial claim: may not pass S3 (load-bearing).

p,p'-DDE reduces erectile functions in rats.

“Other environmental antiandrogens, such as p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE), have already been shown to reduce erectile functions in rats (Brien et al. 2000).”

• cites Brien et al. 2000 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

All three fungicides (Vz, procymidone, iprodione) have the same final metabolite.

“All three fungicides have the same final metabolite.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Only 2 of 47 animals were inactive during both penile reflex sessions and were dropped from the analysis.

“Only 2 of 47 animals were inactive during both sessions.”

Classified as probably not a substantial claim. May combine two claims.

The litter always served as the statistical unit of analysis, with exposure level as a between-litter factor and sex and PND as within-litter factors.

“The litter always served as the statistical unit of analysis, with the exposure level as a between-litter factor and sex and PND as within-litter factors.”

May combine two claims.

Stimulation of D1 receptors in the medial preoptic area has the opposite effect to D2 stimulation and occurs at much lower doses.

“stimulation of D1 receptors in the medial preoptic area has the opposite effect and occurs at much lower doses (Hull et al. 1992).”

• cites Hull et al. 1992 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In developing males, prenatal exposure to antiestrogens impairs copulatory performance without disturbing sexual motivation.

“In developing males, prenatal exposure to antiestrogens (Matuszczyk and Larsson 1995) also appears to impair copulatory performance without disturbing sexual motivation.”

• cites Matuszczyk and Larsson 1995 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In adult male rats, castration, lesions of the medial preoptic area, or microinjection of dopamine antagonist drugs can produce effects similar to those of Vz.

“In adult male rats, a number of manipulations can produce similar effects, including castration (Leipheimer and Sachs 1993), lesions of the medial preoptic area (Everitt 1990), or microinjection of dopamine antagonist drugs (Pfaus and Phillips 1991).”

• cites Leipheimer and Sachs 1993 sourceNot checked — no full text of the source
• cites Everitt 1990 sourceNot checked — no full text of the source
• cites Pfaus and Phillips 1991 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S4 (based).

Animal studies indicate that fetal males are far more sensitive to environmental antiandrogens than adults.

“As mentioned above, animal studies indicate that fetal males are far more sensitive to environmental antiandrogens than adults.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Pregnant rat dams were assigned to an exposure condition according to a randomized block design.

“Pregnant rat dams were placed individually into polycarbonate shoebox cages and assigned to an exposure condition according to a randomized block design.”

Classified as probably not a substantial claim. May combine two claims.

The litter was always considered the unit of analysis, and only 1 male and 1 female pair per litter was assigned to the play procedure.

“The litter was always considered the unit of analysis, and only 1 male and 1 female pair per litter was assigned to the play procedure.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In earlier investigations, during copulation, exposed males mounted but were unable to achieve vaginal penetration.

“during copulation, exposed males mounted but were unable to achieve vaginal penetration (Gray et al. 1994).”

• cites Gray et al. 1994 sourceNot checked — no full text of the source

Classified as probably not a substantial claim. May combine two claims.

Male rat play behaviors peak earlier, during PND26-35, while female behaviors peak during PND36-40.

“Male behaviors peak earlier, during PND26–35, with female behaviors peaking during PND36–40 (Meaney and Stewart 1981).”

• cites Meaney and Stewart 1981 sourceNot checked — no full text of the source

May combine two claims.

Both serotonin receptor agonists and nitric oxide synthesis blockers reduce erections and increase seminal emissions.

“Both of these treatments reduce erections and increase seminal emissions.”

May combine two claims.

Pharmacologic stimulation of dopamine D2 receptors in the medial preoptic area decreases the frequency of erections while increasing seminal emissions.

“pharmacologic stimulation of dopamine D2 receptors in the medial preoptic area decreases the frequency of erections while increasing seminal emissions (Bazzett et al. 1991).”

• cites Bazzett et al. 1991 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

All of these procedures produce structural or functional changes in the erectile system.

“All of these procedures produce structural or functional changes in the erectile system (Hull et al. 1992; Monaghan et al. 1993; Warner et al. 1991).”

• cites Hull et al. 1992 sourceNot checked — no full text of the source
• cites Monaghan et al. 1993 sourceNot checked — no full text of the source
• cites Warner et al. 1991 sourceNot checked — no full text of the source

May combine two claims.

The exposed offspring resemble males castrated as adults, which also show an early reduction of E1 erections.

“In this regard, the exposed offspring resemble males castrated as adults, which also show an early reduction of E1 erections (Leipheimer and Sachs 1993).”

• cites Leipheimer and Sachs 1993 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Peripubertal exposure to higher doses of Vz delays the age of preputial separation in male rats.

“Peripubertal exposure to higher doses of Vz has been shown to delay the age of preputial separation, which is a milestone of puberty in the male rat (Monosson et al. 1999).”

• cites Monosson et al. 1999 sourceNot checked — no full text of the source

May combine two claims.

Earlier work found reduced AGD in male neonates and nipple retention after maternal doses as low as 3.125 mg/kg, whereas at least 50 mg/kg was required to affect ventral prostate weight and increase hypospadias incidence.

“Earlier work found that reduced AGD in male neonates and nipple retention occurred after exposure to maternal doses as low as 3.125 mg/kg, whereas at least 50 mg/kg was required to affect ventral prostate weight and increase the incidence of hypospadias (Gray et al. 1999a).”

• cites Gray et al. 1999aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Data on prenatal morphine suggest that the onset of the critical period for play is GD16.

“Data on the effects of prenatal morphine suggest that the onset of the critical period for play is GD16 (Niesink et al. 1999).”

• cites Niesink et al. 1999 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Stimulation of D2 receptors in the paraventricular nucleus facilitates seminal emission.

“Stimulation of D2 receptors in the paraventricular nucleus also facilitates seminal emission (Eaton et al. 1991; Pehek et al. 1989).”

• cites Eaton et al. 1991 sourceNot checked — no full text of the source
• cites Pehek et al. 1989 sourceNot checked — no full text of the source

May combine two claims.

Both estimated daily intakes exceed the ED10 benchmark doses associated with altered juvenile play behavior and erectile dysfunction in the authors' animal model.

“Both of these estimated daily intakes exceed the ED10 benchmark doses associated with altered juvenile play behavior and erectile dysfunction in our animal model.”

May combine two claims.

A 2-year-old boy weighing 13 kg would consume an average of 2.17 mg Vz/day, and a 6-year-old weighing 21 kg would consume an average of 3.51 mg Vz/day.

“a 2-year-old boy who weighs 13 kg [Centers for Disease Control and Prevention (CDC) 2000] would consume an average of 2.17 mg Vz/day, whereas a 6-year-old with a body weight of 21 kg would consume an average of 3.51 mg Vz/day.”

• cites Centers for Disease Control and Prevention (CDC) 2000Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Occupational exposure to stilbene is associated with an increase in self-reported impotence and decreased libido.

“Occupational exposure to stilbene has also been associated with an increase in self-reported impotence and decreased libido (Quinn et al. 1990; Whelan et al. 1996).”

• cites Quinn et al. 1990 sourceNot checked — no full text of the source
• cites Whelan et al. 1996 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Both clinical studies examined the effects of exposure during adulthood.

“Both of these clinical studies examined the effects of exposure during adulthood.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

The internal dose of Vz and/or metabolite in fetal or neonatal subjects was lower than the applied maternal dose.

“The actual amount of Vz and/or metabolite that entered our fetal or neonatal subjects is unknown, although the level was certainly lower than the applied maternal dose.”