Forty-nine chemicals were tested in a mouse bone marrow micronucleus test that employed three daily exposures by intraperitoneal injection. Bone marrow samples were obtained 24 hr following the final exposure. Twenty-five rodent carcinogens and 24 noncarcinogens were selected randomly from the 44 carcinogens and 29 noncarcinogens used by Tennant et al. (Science 236:933-941, 1987) to evaluate the performance of four in vitro genetic toxicity tests. As in that study of in vitro tests, the micronucleus tests were conducted with coded chemicals and test results (positive or negative) were determined prior to decoding. This study was conducted as part of an effort to assess the ability of the micronucleus test to discriminate between rodent carcinogens and noncarcinogens and to determine its potential role, in combination with other short-term tests, in identifying genotoxic chemicals that present a carcinogenic hazard. Nine chemicals were judged to be positive in the micronucleus test. This relatively low number of positive results, along with published and unpublished results from rodent micronucleus and chromosome aberration assays on several of these 49 chemicals, contributed to the conclusion that a single micronucleus test protocol is not adequate to detect all chemicals capable of inducing chromosomal damage in the bone marrow. However, a combination of two relatively simple assays such as the Salmonella and micronucleus tests can provide important information on the genetic toxicity of test chemicals and may provide guidance on the need for and the nature and extent of future toxicity studies.

B a r ry S . L y n ch , D ou g la s W . B ry a n t , G ra h a m J . H ook , E a r le R . N est m a n n , a n d I a n C . M u n ro C a n Tox, I n c, M is s is s a u g a , O n t a r io, C a n a d a -M on och l or o-1 ,2 -p r op a n ed i ol (-M C P D ) i s a b y -p r od u ct f ou n d i n t r a ce a m ou n t s , gen er a l ly l es s t h a n 1 m g/ k g (<1 p p m ), in h y d rol yz ed v eget a b l e p r ot ein p r od u ced t h rou gh a cid h y d r ol y si s. I n a ch r on ic s t u d y w it h F 4 4 r a t s , h igh d os es of -M C P D p r od u ced ben ig n r en a l t u m or s i n bot h s ex es a n d L ey d i g-cell a n d m a m m a r y t u m or s in m a l es . 3-M C P D is gen ot ox i c in v it r o, b u t t h er e is n o ev id en ce of gen ot ox i ci t y in v i v o. T h er e is som e q u es t ion a b ou t t h e m ech a n is m res p on s ib le for t h e ca r ci n og en i ci t y of -M C P D in cer t a in sp eci es . H er e w e p r esen t a cr i t ica l r ev i ew of t h e t ox icol ogica l , m et a bol ic, a n d m ech a n i s t ic d a t a on -M C P D . O n t h e b a si s of t h is r ev i ew , t h e t u m or s r ep ort ed i n F 4 4 r a t s a r e concl u d ed t o h a v e d ev elop ed a s a r es u lt of n on gen ot ox i c m ech a n is m s a n d a re consi d ered n ot t o be relev a n t t o h u m a n s ex p os ed t o t r a ce a m ou n t s of -M C P D . T h i s con clu s ion w a s b a sed on t h e l a ck of ca r ci n ogen i ci t y of -M C P D in m ice or S p r a gu e-D a w ley r a t s ; t h e b en i gn n a t u r e of t h e t u m ors i n v ol v ed ; t h e d ep en d en ce of t h e L eyd i g-cell a n d m a m m a r y t u m or s on s p ecies-a n d st r a in -d ep en d en t m ech a n is m s in v ol v i n g ch r on ic ch a n ges i n h or m on e b a la n ce; t h e a ss oci a t i on of t h e ren a l t u m or s w i t h ch r on ic n ep h r op a t h y a n d n ep h r ot ox i ci t y ; a n d d if feren ces b et w een b a ct eri a l a n d m a m m a l ia n s ys t em s in t h e m et a b ol is m of -M C P D t h a t li k el y a ccou n t f or it s g en ot ox ic a ct iv it y i n cert a i n in v i t r o t est s y st em s . A t t r a ce lev el s in food s, M C P D is con si d er ed n ot t o p os e a ca rcin ogen ic r i sk t o h u m a n s .K e y w o r d s ca r cin og en icit y, ch lor oh yd r in , 3 -ch lor o-1 ,2 -p r op a n ed iol, ge n ot oxicit y, h or m on a l in d u ct ion , L e yd ig ce ll C h e m ica ls in t h e food s u p p ly a r e r e g u la t e d w it h r e s p e ct t o t h eir t oxicolog ica l e ffe ct a n d t h e a n t icip a t e d e x p os u r e le v e ls in t h e p op u la t ion . Am on g t h e cr it e r ia t h a t ch a r a ct e r ize t h e p ot en t ia l a d v er s e e ffe ct of a ch e m ica l in food is it s cla s s i® ca t ion a s n on ca r cin oge n , g e n ot oxic ca r -In t e r n a t i o n a l J o u r n a l o f To x i c o l o g y, 1 7 :4 7 ± 7 6 , 1 9 9 8 47 C o p y r i g h t Ó 1 9 9 8 Ta y l o r & F r a n c i s 1 0 9 1 -5 8 1 8 /9 8 $ 1 2 .0 0 + .0 0

The mouse peripheral blood micronucleus (MN) test was performed on samples collected from 20 short-term, 67 subchronic, and 5 chronic toxicity and carcinogenicity studies conducted by the National Toxicology Program (NTP). Data are presented for studies not previously published. Aspects of protocol that distinguish this test from conventional short-term bone marrow MN tests are duration of exposure, and absence of repeat tests and concurrent positive controls. Furthermore, in contrast to short-term bone marrow MN tests where scoring is limited to polychromatic erythrocytes (PCE), longer term studies using peripheral blood may evaluate MN in both, or either, the normochromatic (NCE) or PCE populations. The incidence of MN-PCE provides an index of damage induced within 72 hr of sampling, whereas the incidence of MN in the NCE population at steady state provides an index of average damage during the 30-day period preceding sampling. The mouse peripheral blood MN test has been proposed as a useful adjunct to rodent toxicity tests and has been effectively incorporated as a routine part of overall toxicity testing by the NTP. Data derived from peripheral blood MN analyses of dosed animals provide a useful indication of the in vivo potential for induced genetic damage and supply an important piece of evidence to be considered in the overall assessment of toxicity and health risk of a particular chemical. Although results indicate that the test has low sensitivity for prediction of carcinogenicity, a convincingly positive result in this assay appears to be highly predictive of rodent carcinogenicity.

To determine whether exposure to radiofrequency (RF) radiation can induce DNA damage or apoptosis, Molt-4 T lymphoblastoid cells were exposed with RF fields at frequencies and modulations of the type used by wireless communication devices. Four types of frequency/modulation forms were studied: 847.74 MHz code-division multiple-access (CDMA), 835.62 MHz frequency-division multiple-access (FDMA), 813.56 MHz iDEN(R) (iDEN), and 836.55 MHz time-division multiple-access (TDMA). Exponentially growing cells were exposed to RF radiation for periods up to 24 h using a radial transmission line (RTL) exposure system. The specific absorption rates used were 3.2 W/kg for CDMA and FDMA, 2.4 or 24 mW/kg for iDEN, and 2.6 or 26 mW/kg for TDMA. The temperature in the RTLs was maintained at 37 degrees C +/- 0.3 degrees C. DNA damage was measured using the single-cell gel electrophoresis assay. The annexin V affinity assay was used to detect apoptosis. No statistically significant difference in the level of DNA damage or apoptosis was observed between sham-treated cells and cells exposed to RF radiation for any frequency, modulation or exposure time. Our results show that exposure of Molt-4 cells to CDMA, FDMA, iDEN or TDMA modulated RF radiation does not induce alterations in level of DNA damage or induce apoptosis.

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