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

ATRAZINE
First draft prepared by
Rudolf Pfeil, 1 Vicki Dellarco 2 and Les Davies 3
1
Toxicology of Pesticides, Federal Institute for Risk Assessment, Berlin, Germany;
2
Office of Pesticide Programs, United States Environmental Protection Agency,
Health Effects Division, Washington, USA; and
3
Chemical Review, Australian Pesticides and Veterinary Medicines Authority,
Canberra, Australia
Explanation ........................................................................................................ 38
Evaluation for acceptable daily intake ............................................................... 39
1. Biochemical aspects ............................................................................. 39
1.1 Absorption, distribution and excretion ......................................... 39
1.2 Biotransformation ........................................................................ 42
2. Toxicological studies ........................................................................... 44
2.1 Acute toxicity................................................................................ 44
(a) Lethal doses ......................................................................... 44
(b) Dermal irritation .................................................................. 47
(c) Ocular irritation ................................................................... 49
(d) Dermal sensitization............................................................. 49
2.2 Short-term studies of toxicity ....................................................... 49
2.3 Long-term studies of toxicity and carcinogenicity ....................... 51
2.4 Genotoxicity.................................................................................. 64
2.5 Reproductive toxicity ................................................................... 64
(a) Multigeneration studies ....................................................... 64
(b) Studies of developmental toxicity ....................................... 68
2.6 Special studies .............................................................................. 71
(a) Studies on metabolites .......................................................... 71
(b) Studies on site and mechanism of action in the central
nervous system ..................................................................... 86
(c) Studies on effects on estrous cycle or LH surge ................... 88
(d) Studies on reproductive and developmental effects ............. 93
(e) Studies on female pubertal development ............................. 95
(f) Studies on male pubertal development ................................. 96
(g) Studies on development of the mammary gland .................. 98
(h) Studies on estrogenic and anti-estrogenic potential ........... 100
(i) Studies on aromatase activity or gene expression .............. 101
(j) Studies on adrenal steroidogenesis...................................... 102
(k) Studies of immunotoxicity ................................................. 103
3. Observations in humans ..................................................................... 105
Comments ........................................................................................................ 108
Toxicological evaluation .................................................................................. 112
ATRAZINE 37–138 JMPR 2007