Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

123
Table A2. Comparison of parameters of reproductive senescence in female Sprague-Dawley rats,
female Fischer 344 rats and humans
Parameter Sprague-Dawley rats Fischer 344 rats Humans
Start of senescence (% of
normal lifespan)
30–40% 60–70% 60–70%
Principle cause of
senescence
Hypothalamic failure to
stimulate LH/FSH
Hypothalamic failure to
control prolactin surges
Depletion of ovarian follicle
content
LH-surge capability Lost Maintained Maintained
Predominant cycle pattern Persistent estrus Pseudopregnancy episodes Menopause
Estrogen/progesterone ratio Elevated/prolonged Reduced Reduced
Prolactin secretion Persistently elevated Episodically elevated Reduced
Spontaneous incidence of
mammary tumours
(lifetime)
30–40% 2–5% 8–10%
Principal known factors that
increase risk of mammary
tumour s
Prolactin, estrogen,
chemical mutagens
Prolactin, estrogen,
chemical mutagens
Family history, parity, diet,
and body weight
Prolactin dependence High Median None
From Simpkins et al. (2000)
LH, luteinizing hormone; FSH, follicle-stimulating hormone.
insulin resistance and altered metabolism of carbohydrate and lipid. An association between the
occurrence of PCOS and endometrial hyperplasia and/or cancer has been reported and is biologically
plausible on the basis of estrogenic stimulation of the endometrium unopposed by progesterone. Epidemiological
evaluation of the association between the occurrence of PCOS and ovarian and breast
cancer is not compelling (Eldridge & Delzell, 2000a).
In contrast to women with PCOS, female Sprague-Dawley rats treated with atrazine at high
doses display decreased LH, decreased or unaltered concentrations of androgen, weight loss and no
association with endometrial or ovarian cancer. The earlier appearance and/or elevated incidence of
mammary tumours observed in female Sprague-Dawley rats is attributed to persistent exposure to
endogenous estrogen and prolactin resulting from an earlier failure of the neuro-endocrinological
control mechanisms that regulate the estrous cycle in this strain of rat.
Hypothalamic amenorrhoea (HA) is characterized by decreased activity in the hypothalamic–
pituitary ovarian axis and low-level exposure to endogenous estrogen (Eldridge & Delzell, 2000b).
Amenorrhoea may occur as a result of a diverse number of conditions, including stress, anorexiainduced
weight loss, exercise-induced weight loss or failure to gain weight, and the occurrence of
lactation, and results in failure to have a normal menstrual cycle. Amenorrhoea, from whatever cause,
is generally associated with a decreased risk for developing endocrine-mediated tumours in the
breast, ovary and uterus. Exposure to atrazine would not lead to a state of persistently increased concentrations
of estrogen in women and would not cause an increased incidence of estrogen-mediated
tumours in women.
In contrast to hypothalamic amenorrhoea in women, female Sprague-Dawley rats given atrazine
at high doses experience prolonged periods of high-level stimulation of estrogen-sensitive tissues
by endogenous estrogens (endocrine ageing), which leads to the earlier appearance of mammary
tumours.
ATRAZINE 37–138 JMPR 2007