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January 21. 1977
J. R. Hcfleooegh, M.B. TtniNitM Eastwea Goapeny 9. 0. Box 611 Kingsport, Tannessaa 37662
Pear Or* WePonowgh,
Dan Tain hit passed on to w a copy of yonr 6rtft on "Developing Approaches to Toxicology Totting.11 Onfortunately. I 414 not receive the draft until January 19 and to obviously could not Ian wants to you by January 17. Otbors appeared to have and* mm dotalled coMonts, to I will nafco only a couple of canonts vend suggestions.
In tbo Introduction, you state. "Hi nst at all cotta avoid the grin saga of Kit* vinyl .chloride* and asbestos.* ^ Than* In the ... ..v'k^yr'.nat lino you go on te say that It It not certain that can avoid ' tuck occurrences In the future. I doubt If wa art willing to accept the cost of not doing any further dovolopnat of nou dmncals In order to avoid another gHn saga. Ua art willing to aedapt ton level of risk In order to obtain the benefits that wo way be able to derive ffea a new notorial. I believe It would he baneful to the chadcal Industry to have one of our representatives quoted os saying that wa wst at all costs avoid such Incidents.
In the next te the last paragraph an page 7. you give tba cost of carcinogenicity study ns being In tin raugo of $100,000. lohalatloo carcinogenicity studios Involving two species ere presently testing 3900*009 to 3400,000. I believe that the 3100,009 figure nay he too lew end Misleading.
hnletlve to Onorga login's ceuuent on cast effectiveness, there Is
sew logic Innpetting the km type ef testing* tire dodnaftt lethal
tests, end the teratogenicity testing hofnm the llfetlan cardno* gnnlclty tests. I believe that If wa had Strong positives In nil three ef these tests, we eoeld take a hard look et the probable profitability before coaduing 1399,009 for to Inhalation carcino genicity test.
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J. R. McDonough* H.O. tag* 2 Jamary 21* 1977
There Bight b* mm aentloo node ef fish and wildlife tests site* TOSCA does specify effects on the environment?' as Mil as affects on health of toaaos.
1 appreciate the privilege of being able to read the draft of peer presentation and tope that the above canents any be of sem value to you. You have undertaken an extaanly difficult task and have de7 veloped a fine suaoary of the state of the art.
Very truly yours
RH:pea cc: D. 0. tala
Richard Henderson* Ph.D. Director, Health Sciences
and Toxicologic Research
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slide 1
TOXICOLOGICAL TrlOTING
Tents currently tivn j 1 till e KeliuliJ Xlty Informal!on derived from lent Li mituti oun Approach under the law
lide 2
Acute Study (Pause finding) Prolonged (Subchronic) Chronic
Slide 3
Carcinogenicity G--
Mut/genleity
Teratogenicity
Slide 1
Sample Acute Teat
Kale Bata *150-200") ,
5 at 1ov doae 5 nt j rtermed i ate doae [j at lii (;h doae
Material ly mouth
Obacrved 7-l'i dnya
.Standard diet
LlVjQ calculation
de 5
Tent Acute oral 1/PyO - 2 species
Sort $1,000-1,200
Time
6 \reeks
Slide 6 I
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. Slide 7
Prolonged Tent
Tints (nr dor,''-)
3 0-70 control
3 0-70 3o',.1 ilo. e
3 0-/0 i titejr.'K'-i i :iti- done
30-/0
done
Administration - Ity mouth, i nhnlnti on, 3nt1oni,ion, skin
Duration 'tO to 9 day::
Slide 8
Prolonged Test (conti m;od )
Periodic evaluation of cnimals Body we.if.dit Physical. Pxnm Blood chemistries Urinniynia ilematoloffy
Observation of Anino!s Activity Behnvi or General appearance
Animals rubjeet to autopsy and ]ji .<;to3 o^v
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Slide 9
Tc- s t Prolonged (gulchroni c ) Studies
90 day rat feeding 90 day do;1, Coed in/1;
Cost
$.12-1-.000 .f.lY-20000
Time 6 month
Slide 10
Carcinogenicity Tent
R&ts or mice Total
POO animals 50 in each of k donate groups 100 animals in control group
'iOO animals
Route of /ulin.in. - oral, inhnlotion, skin, other
Duration - ? to 3 years
K
Ohservnti one. - Llood chc-mi stri es, hematology, pharmoco/inetic
studies, vc-i.gilt changes, general demeanor. .
SI ide 11
Test Chronic Feeding Study (Comer) Rat 2 yr. Dog 2 yr.
Cost
Time
.f.70-90,000 $00-100, 000
3O months 30 months
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Slide 12
llutogcnicity Teste
Cytogenetic Analysis Mutation in mi croorgani nne
'(1 i/it(*`l assay Dominant Lethnl DIM repair studies
Slide 13
Muiogeni city Cindies Host-mediated assay Dominant Lethal Cytogenetic Studies
Coat $2-2500 ${1-9000
Time 2-3 months
4 months 4 months
Slide 14
Food Uousing Climate Diological factors
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Slide 15
20 control
fiO Female rote
20 low d 03c 20 i ntermc-u i ate dose
20 high dope
Dosage - c'lai'Jy during day 6-15 of pregnancy.
Observations
Slide 16
Autopsy - 1. Spontaneous deaths and moribund animals. 2. Survivors on day 30 of pregnancy 3- lixami noti one Term ietur.es - weighed, measured and examined
Slide IT
Test Rat Mouse Monkey
Cost $7-15,000 $6-9,000 $50-65,000
Time inos. inos. 3^-16 mor,
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