Effects on fertility

Male patients with RA must receive counseling about the effects of certain medications on their fertility and potential harm to the fetus. It is difficult to establish causality between use of a medication by a male and the effect on fertility or fetal development therefore, a conservative approach must be taken. Patients of childbearing potential and their partners must be counseled to (1) use proper birth control while undergoing treatment for RA and (2) discontinue medications at least 3 months before conception.37... 

Johansson L, Wide M. 1986. Long-term exposure of the male mouse to lead Effects on fertility. 

Fulcher SM Rifaximin Combined Study of Effects on Fertility and Embryo-Fetal Toxicity in CD Rats by Oral Gavage Administration. Eye, Huntington Life Sciences, 2000. 

Egg 65 No effect on fertilization membrane formation or development in eggs transferred 1 min after insemination 46... 

No effect on fertilization success or embryo survival after adults exposed for 28 days 8... 

Dibutyl sebacate was tested for reproductive toxicity in a dietary study with Sprague-Dawley rats 6.25% (approximately 5.6 g/kg/d) in the diet for 10 wk prior to breeding (Smith 1953). No effect on fertility, litter size, or pup survival was found. However, pups from treated dams weighed less than pups from the control group. 

It is not known if exposure to //-hexane can affect fertility in people. Experiments done with animals that were fed or breathed in //-hexane did not show any effect on fertility. 

Not only is it difficult to detect effects on male fertility because of group-size considerations, effects on male fertility mediated by decreased sperm production are also difficult to detect because of the normally huge excess of sperm included in a rat ejaculate. Sperm production can be decreased by up to 90% without effect on fertility (either pregnancy rate or litter size) in the rat. This is not the case for men, so the sperm excess in the rat represents a serious flaw in the rat model (see Working, 1988). To address this deficiency and improve the sensitivity of the model, it is advisable to determine the effects of the test agent on testes weights, testicular spermatid counts, and histopathology of the testes (preferably plastic sections) in the male fertility study and/or the 14-week toxicity study. In some cases, these parameters may be more predictive of possible effects on male fertility in humans than the fertility rate in rats. 

Reproductive Effects. Antispermatogenic effects and possible effects on fertility have been reported in humans occupationally exposed to 1,2-dibromoethane (Heinrichs 1983 Ratcliffe et al. 1987 Ter Haar 1980 Wong et al. 1979). However, many of these studies lacked sufficient statistical power to detect an association between parameters measured and exposure. 

Ideally, a full data set should be available for the hazard assessment of a chemical substance, including animal tests to evaluate the toxicokinetics and the following toxicological properties acute toxicity, irritation, sensitization, toxicity following repeated exposure to the substance, mutagenicity and genotoxicify, carcinogenicity, and effects on fertility and fetal development. 

Sakamoto J, Hashimoto K Reproductive toxicity of acrylamide and related compounds in mice—effects on fertility and sperm morphology. Arch Toxicol 59 201-205, 1986... 

In rats the oral LDso values for borates are essentially the same as for boric acid they range from 3.16 to 6.08 g/kg." When borax was fed to dogs and rats for 2 years, 3 50 ppm as boron in the diet had no effect. In a three-generation feeding study in rats, 350ppm had no effect on fertility, litter size, weight, or appearance. 

Several studies in rats, mice, and rabbits demonstrate that cycloheximide is embry-otoxic, fetotoxic, and teratogenic. Intraperi-toneal administration of doses as low as 250 pg/kg on day 10 of gestation produced central nervous system, craniofacial, and cardiovascular system abnormalities in rats. Musculoskeletal abnormalities were produced in mice after intraperitoneal administration of doses as low as 30mg/kg on day 9 of gestation. Subcutaneous administration of 5 mg/1 cycloheximide on day 11 caused postimplantation mortality in the mouse. Effects on fertility were observed in pregnant rabbits administered as little as 5 pg/kg on day 1 of gestation. 

No detrimental effect on fertility has been found in occupationally exposed workers where exposure levels are estimated to be less than 1 ppm. ... 

John JA et al Inhalation toxicity of epichlorohydrin Effects on fertility in rats and rabbits. Toxicol Appl Pharmacol 68 415-423, 1983... 

No effect on fertility was seen in male rats treated orally." Hexylene glycol was not geno-toxic in a variety of assays." ... 

Metbomyl did not produce embryotoxic or teratogenic effects in rats or rabbits at doses that caused maternal toxicity No effects on fertility, gestation, or lactation indices were found in three-generation reproduction studies in rats. ... 

No adverse effects on fertility, reproduction, or parturition were found when male and female rats were treated with sodium metavanadate by gavage and then mated. ... 

Fertility Impairment Results of animal studies suggest the possibility of a general adverse effect on fertility in males and females. 

A variety of cell-based and animal-based studies can be performed to ensure that a new chemical does not cause reproductive or developmental effects. A battery of tests is done to ensure that there are no harmful effects on fertility. Teratogenicity studies are performed to ensure that the chemical does not cause physical malformations in the offspring from exposure during pregnancy. Multiple generations of animals may be continuously exposed to ensure that a compound is safe. 

However, in that combination study there is the potential risk of having effects on fertility in one or both sexes that would limit the number of litters available for evaluation of fetal morphology. The need to assess two species in the EFD study, to access both sexes in the fertility study, and the complexities of the PPN study make the three-study option the most practical and least risky. 

For classification and labelling, there are standard categories that apply to teratology data (similar categories also apply to effects on fertility, but these are outside the scope of this chapter) ... 

The vagina, uterus, and ovaries of all females and the seminal vesicles, prostate gland, right testis, right epididymis, and left caput epididymis of all males are preserved for possible histological examinations (1). Further examinations are only performed if a treatment-related effect on fertility is suspected. 

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