Impairment of Fertility

Substances which can impair the fertility are classified as toxic to reproduction. Following the general rules mentioned in Section 3.3.1, substances of category 1 and 2 are labeled with the danger symbol T and the indication of danger toxic . The reproductive property is expressed with the R-phrase R 60. 

Benzo[a]pyrene 4-Chlorobenzotrichloride 2,3-Epoxy-1-propanol (Glycidol) 

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Toxicity studies in animals have failed to show evidence of damage in any tissue examined after 3 months administration to rats of daily doses up to 20 000 times that required to produce diuresis. Similar absence of effect on all vital organs was found in dogs and rhesus monkeys. No teratogenesis or impairment of fertility was detected. Very large doses (up to 10 000 mg/kg) failed to produce ill-effects in acute toxicity tests on rats, though intravenous LDjo values were in the region of 230 mg/kg. 

Fertility Impairment Impairment of fertility, oligospermia, and menstrual dysfunction in humans has been reported during and for a short period after cessation of therapy. 

Return of fertility may be delayed for several months after withdrawal of medroxyprogesterone acetate. The length of the delay is not related to the duration of use. There is no evidence of permanent impairment of fertility (2,34). 

Sexual complaints attributed to interferon alfa, namely decreased hbido, impotence, or erectile failure, are usually concomitant to other neuropsychiatric symptoms, and cases of reversible impotence are anecdotal (315). The mechanisms accounting for these adverse effects are unclear, and changes in sex hormone concentrations have not been consistently reported. In one study in healthy women, interferon alfa produced falls in serum progesterone and estradiol concentrations (316), but neither impairment of libido nor impairment of fertility has apparently been reported in women. No evidence of gonadal toxicity or sexual dysfunction was found in 43 men with hairy cell leukemia who received interferon alfa for 2-12 months compared with 33 patients who... 

Crystalluria and secondary nephropathy were noted, especially under conditions of alkaline urine. No impairment of fertility was noted and no congenital defects could be directly related to the administration of the drug. 

Tamoxifen produced impairment of fertility and conception in female rats. No genotoxic potential was found in conventional in vivo and in vitro tests. 

Considerable uncertainty remains concerning the impairment of reproductive function by lead. Eor males, there are several studies indicating that only B-Pb levels above 400 pg L are connected with impairment of fertility. 

Carcinogenesis, Mutagenesis, Impairment of Fertility In a 2-year study in Sprague-Dawley rats, albuterol sulfate caused a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium at dietary doses of 2, 10, and 50 mg/kg (approximately 1/2, 3, and 15 times, respectively, the maximum recommended daily oral dose for adults on a mg/m basis, or, 2/5, 2, and 10 times, respectively, the maximum recommended daily... 

Studies on the reproductive function (three generations) and intrauterine development of rat showed no impairment of the rate of fertility and no sign of any teratogenic effect. The Ames test on mutagenicity was negative [101]. 

It is known that more fetal wastage than generally believed and many spontaneous abortions arise as a result of the presence of dominant lethal mutations in the developing embryo, many of which appear to be due to major chromosomal damage. In addition, impairment of male fertility may also be a consequence of exposure to mutagens. 

Fertility Impairment It is considered probable that in humans, valganciclovir at the recommended doses may cause temporary or permanent inhibition of spermatogenesis. Animal data also indicate that suppression of fertility in females... 

The second objective of the hazard assessment concerns characterization of the identified hazards of a particular substance. Under REACH this means that the registrant must define so-called derived no-effect levels., abbreviated DNELs. With respect to human health, these values constitute exposure levels above which humans should not be exposed and below which risks for humans are considered controlled. The DNEL derivation is a complex process which comprises several conversion steps and the application of different assessment factors. In the case of reproductive toxicity, the registrant derives separate DNELs with respect to developmental toxicity on the one hand and to impairment of sexual function and fertility on the other hand. 

Ovary histopathology Mating-, impairment of hormone production leading to lack of appropriate mating behavior and/or estrous cycle abnormalities Fertility reduced ovulation... 

Exposure by inhalation to methyl chloride causes fetal growth retardation and impaired male reproductive capacity in rats and malformations of the heart in fetal mice (lARC, 1986). The preimplantation losses described in rats in which the males were exposed to 6300 mg/m methyl chloride for 6 h per day for five days were due to a failure of fertilization rather than preimplantation embryonic death. A concentration of 2100 mg/m3 had no effect upon fertilization (Working Bus, 1986). 

Au artificial mixture can be theoretic ally compounded to take the place of farmyard manure, but it must contain all its mineral constituents. The agriculturist must return to the land whatever has been removed from it for it has been laid down as a rule, that no part of the constituents of a rich soil can bo removed without making compensation, but at the cost of sooner or later impairing its fertility. 

In animals (particularly monkeys), cannabis depresses ovarian and testicular function. In man, chronic use has been associated with reduced serum FSH and LH concentrations in a few people, often accompanied by reduced serum testosterone, oligospermia, reduced sperm motility, and gynecomastia (235). There is no evidence of impairment of male fertility no studies have been carried out on female fertility. There is evidence of slightly shortened gestation periods in chronic users (236). There are variable non-specific effects on serum prolactin and growth hormone and a rise in plasma cortisol concentrations has been recorded in one study. 

Xenobiotics can adversely affect the normal functions of the cells/organs of the reproductive system. These agents may induce a variety of outcomes, including prevention of ovulation and impairment of ovum transport, fertilization, or implantation. Endocrine disruptors may mimic endogenous hormones as well as directly destroy cellular components, leading to cell death. More indirect effects may include inhibition of key enzymes involved in steroid synthesis. 

For freshwater invertebrates, frequently used species are the pelagic crustacean Daphnia magna and the sediment-dwelling insect Chironomus sp., while marine crustacean test methods have used copepods and mysids. Molluscs and echinoderms are also important invertebrate species for developmental and reproductive effects assessment (EC 2003). Reproductive and developmental inhibition may be caused by both endocrine and nonendocrine modes of action however, based on current knowledge, PNEC assessments should be based on impaired fitness parameters (e.g., reduced rates of fertility, development, or fecundity) and not on molecular or biochemical changes (Ingersoll et al. 1999 Hutchinson 2002 Barata et al. 2004). 

C4. Chetkowski, R. J., Kiltz, R. J., and Salyer, W. R., In premature luteinization, progesterone induces secretory transformation of the endometrium without impairment of embryo viability. Fertil. Steril. 68, 292-297 (1997). 

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