Document 0gaj06Z1KnRzYzwgOZwJxZjjb
ETHYL CORPORATION
INTER-OFFICE
To Gary Ter Haar
Address
^3/4
From Subject
Theodore J. Benya
Comparison of Vinyl Chloride Two-Year Toxicity Studies: CIVO1 versus C. Maltoni2
Address
Date
May 3a, 1979
/
I. CIVO Calculations
a) Assumptions;
Rat Weight: Daily Food Intake: Administration: Duration of Exposure: Absorption Efficiency:
0.4 kg 20 g 4 hrs./day x 5 days/wk. 140 weeks 50% of dose
b) Calculation: (Example)
1% PVC powder (4000 ppm VCM) in feed would pro vide 20 ppm dose assuming 50% absorption.
20 ppm would yield 0.4 mg per 20 g of feed, or 1 mg VCM/kg assuming 0.4 kg rat.
II Maltoni Inhalation ppm Concentration Conversion to ng/kg
a) Assumptions
Rat breathing Rate: Administration: Duration of Exposure: Absorption Efficiency:
100 ml/min. 4 hrs./day x 5 days/wk. 52 weeks 80% of dose
b) Calculations: (Example)
50 ppm = %mg x 24.45 i o o o A 62
50 ppm = 0.1268 mg
Amount Administered Per Day:
50 ppm = 0.1268 mg x { (6%/hr.)
= 3.04^mg/day
(4 hrs./day)
}
Amount Absorbed Per Day/kg Rat: 50 ppm = 3.04 mg/day (30%)/0.4 kg
= 2.43 mg/day/0.4 kg = 6.09 mg/kg
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G.L. Ter Haar/T.J. Benya Vinyl Chloride Two-Year Study May 30, 1979
2
250 500 2500
ppm- 30.4 mg/kg ppm- 60.0 mg/kg ppm- 304 mg/kg
HI* Discussion (See Tumor Incidence Table Attached)
In comparison, the CIVO and Maltoni data appear to be consistent. In contrast, when comparing Maltoni and IBT data (previously reported) the latter indicated a four- to seven fold greater incidence in liver angiosarcomas.
TJB:sbb
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Theodore J. `Benya
i Centraal Instituut Voor Voedingsonderzoek (W. Germany) "Central Institute for Nutrition and Food Research", October, 1978
2 Institute of Oncology and Tumour Centre (Bologna, Italy) "Origins of Human Cancer", Cold Spring Harbor 1977 Con ference . pps. 119-146.
TUMOR INCIDENCE (%) TABLE
Study
Route mg/kg
Liver
Zymbal
Mammary
Angiosarcomas Carcinomas Carcinom;
ClVO Maltoni ClVO Maltoni ClVO Maltoni Maltoni Maltoni Maltoni CIVO Maltoni
Feed Gavage Feed Inhal. Feed Gavage Inhal. Gavage Inhal. Gavage Inhal.
1.7 3.3 5.0 6.0 (50 ppm) 14.1 16.6 30.0 (250 ppm) 50.0 61.0 (500 ppm) 300 304 (2500 ppm)
0 0
5 1.6 22.5 11.2 6.0 20.0 10.0 35 18
0 1.9 00 1.2 2.5 0 3.1 0 5.6 1.2 2.5 0 1.5 0 1.2 6 1.5 1.2 4.4 3 1.4