Endocrine disruptors and testis development.

After serving on a panel convened by the U.S. EPA on epidemiological studies needed for evaluation of possible health risks of MTBE as a fuel additive, I feel that the article is quite informative and will no doubt be useful for those contemplating further use of oxygenated fuels. There are two matters that I feel are of some importance , and about them the article is silent. First, the report of symptoms from use in Fairbanks, Alaska, which stimulated much interest and concern, was associated with two unusual circumstances. First, because of the extreme cold weather, vehicle use is aberrant during the winter in Fairbanks; for example, car motors are left running once they are started. Secondly, the price of fuel increased sharply with the introduction of MTBE, so the public had to realize that there was a change. The second matter was made clear to the panel, but not widely disseminated. It consisted of the protection provided to drivers and service station attendants by the proper use of approved vapor recovery systems during the filling of gasoline tanks. Because such systems also prevent exposures to other fuel ingredients, which may include a certain amount of benzene, for example, they have an added value in health protection from whatever hazards exposure to gasoline may produce. In addition , they also prevent the emission of hydrocarbons, which can be involved in photochemical pollution. Your illustration of filling a gas tank without an approved vapor recovery system is most inappropriate. The article's discussion of cancer risk also omits the reference to the protection such systems may provide. I have advised the EPA that the universal requirement of such vapor recovery systems would have several other benefits to health and the environment, as well as obviating much of the need for further epidemiological studies of cancer risks from MTBE. There is broad experience with such systems, and there are abundant measurements to support this position. Endocrine Disruptors and Testis Development There is currently much debate as to which in vivo tests should be selected for the detection of adverse effects of endocrine disruptors in test animals. As coauthors of a much-cited article in Environmental Health Perspectives (1), which described small (but significant) decreases in testicular weight of adult rats that had been exposed developmentally to either of two environmental estrogens, we would like to bring certain of our experiences to the attention of …

I would like to comment on the article on methyl tertiary butyl ether (MTBE) in the October issue of Environmental Health Perspectives [105: 1042-1043 (1997)].
After serving on a panel convened by the U.S. EPA on epidemiological studies needed for evaluation of possible health risks of MTBE as a fuel additive, I feel that the article is quite informative and will no doubt be useful for those contemplating further use of oxygenated fuels. There are two matters that I feel are of some importance, and about them the article is silent.
First, the report of symptoms from use in Fairbanks, Alaska, which stimulated much interest and concern, was associated with two unusual circumstances. First, because of the extreme cold weather, vehicle use is aberrant during the winter in Fairbanks; for example, car motors are left running once they are started. Secondly, the price of fuel increased sharply with the introduction of MTBE, so the public had to realize that there was a change.
The second matter was made clear to the panel, but not widely disseminated. It consisted of the protection provided to drivers and service station attendants by the proper use of approved vapor recovery systems during the filling of gasoline tanks. Because such systems also prevent exposures to other fuel ingredients, which may include a certain amount of benzene, for example, they have an added value in health protection from whatever hazards exposure to gasoline may produce. In addition, they also prevent the emission of hydrocarbons, which can be involved in photochemical pollution. Your illustration of filling a gas tank without an approved vapor recovery system is most inappropriate. The article's discussion of cancer risk also omits the reference to the protection such systems may provide.
I have advised the EPA that the universal requirement of such vapor recovery systems would have several other benefits to health and the environment, as well as obviating much of the need for further epidemiological studies of cancer risks from MTBE. There is broad experience with such systems, and there are abundant measurements to support this position.
John R. GoIdsmith Ben Gurion University of the Negev Beer Sheva, Israel

Endocrine Disruptors and Testis Development
There is currently much debate as to which in vivo tests should be selected for the detection of adverse effects of endocrine disruptors in test animals. As coauthors of a much-cited article in Environmental Health Perspectives (1), which described small (but significant) decreases in testicular weight of adult rats that had been exposed developmentally to either of two environmental estrogens, we would like to bring certain of our experiences to the attention of readers of EHP and to those involved in framing and implementing regulatory guidelines in this area. * In our original paper, we described small but repeatable effects of gestational and lactational exposure to octylphenol (OP) or butyl benzyl phthalate (BBP) on adult testicular weight and daily sperm production in rats. Two subsequent studies by others (2,3), both of which were more detailed than our own, have failed to find any effect of BBP, despite using very similar or identical protocols to those used by us. We were asked, and agreed, to help in the design of both of these studies, and we are convinced that every effort was made to truly replicate our original experiments, including the inclusion of a positive effect control group exposed to diethylstibestrol (DES). Though none of us involved in these studies is able to offer an explanation for the differences in results obtained, the inconsistency in effect of BBP in these studies should at least give us all pause for thought. We would like to add to this by reporting other recent experiences of ours that we think have an important bearing on the reproducibility of results based on measurement of adult testis weight and the design and interpretation of any test using this endpoint as an indicator of an adverse effect of developmental exposure to hormonally active chemicals.
Approximately 9 months after completion of our study that was published in EHP, testicular weights and body weights in control (untreated/vehicle-treated) animals in our breeding colony began to decline over a period of months. eventually reaching a nadir when the mean ± standard deviation (SD) of testis weight for 36 litters was 1,828 ± 121 mg, compared with the figures of 1,968 ± 163, 2,014 ± 155, and 1,954 ± 118 mg reported in the three experiments in our earlier study (1). This temporal decrease in absolute testis weight in control animals was of comparable magnitude to the most severe treatment effect reported in our paper in EHP (1,750 ± 180 and 1,847 ± 157 mg in Studies 2 and 3, respectively) (1), which resulted from developmental exposure to DES that had been used as a positive effect control. The decrease in testis weight in controls over time is unexplained, but did follow a permanent change in water supply to our animal facility. In the last 18 months or so, testicular weights in control animals in our colony have returned progressively toward the original values and have now stabilized at levels comparable to those we described (1) (1,956 ± 124 mg in the most recent 29 litters).
During the period when control testicular weights were low, developmental exposure of rats to OP (1 mg/1 drinking water), using an identical protocol to that used in Study 3 in our earlier study (1), failed to cause any significant decrease in testis weight; indeed, weights were increased by 7% (1,824 ± 79 mg in controls, n = 7 litters; 1,950 ± 173 mg in OPtreated, n = 15 litters; p<0.1 >0.05). In a subsequent study undertaken when control testis weights had recovered, we were able to confirm a significant effect of DES (50 pg/l drinking water) on absolute testis weight (1,903 ± 146 mg, n = 10 DESexposed litters; 2,050 ± 84 mg, n = 12 control litters; p<0.01) although when expressed relative to body weight, this difference disappeared completely (DES: 4.52 ± 0.30 mg/g body weight; Controls 4.51 ± 0.22; p >0.1). This again contrasts with our original study (though this used 100 pg/l DES). A similar divergence in effect of DES on absolute and relative testis weights was also found in the study by Nair and Jekat (3), whereas Ashby et al. (2) found a significant reduction in both absolute and relative testis weights after developmental exposure to DES. This inconsistency in the effects of DES occurred despite the fact that all three studies used the same dose level (50 pg/1) of DES. These findings add to growing awareness that endocrine disruption data may be difficult to reproduce in different laboratories or between different studies (4), although the reason for these inconsistencies remains obscure.
We are unable to offer an explanation for either the fall/recovery in testicular weights in our control animals or for our failure to obtain similar effects on testis weight/relative testis weight after exposure to OP, and possibly even DES, as we reported originally. We remain confident in the validity of our original published observations, which we consider to fulfill all fundamental scientific criteria with regard to numbers of animals, repeatability of findings, recording