[Federal Register Volume 59, Number 137 (Tuesday, July 19, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-17447]
[[Page Unknown]]
[Federal Register: July 19, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Toxicology Program; Availability of Technical Report on
Toxicology and Carcinogenesis Studies of 1,3-Butadiene
The HHS' National Toxicology Program announces the availability of
the NIP Technical Report on the toxicology and carcinogenesis studies
of 1,3-Butadiene, which is used in the manufacture of synthetic rubber
and of thermoplastic resins.
To better characterize exposure-response relationships for
neoplasms and nonneoplastic lesions, toxicology and carcinogenesis
studies were conducted by exposing groups of male and female
B6C3F1 mice to air containing 1,3-butadiene (greater than 99%
pure) for up to 2 years. An additional study in male B6C3F1 mice,
in which exposure to 1,3-butadiene was stopped after limited exposure
periods (13, 26, 40, or 52 weeks), was performed to assess the effects
of varying concentration and duration of exposure on the incidences of
1,3-butadiene-induced neoplasms.
Groups of 70 male and 70 female mice were exposed to air containing
0, 6.25, 20, 62.5, or 200 ppm 1,3-butadiene for 6 hours per day, 5 days
per week for up to 2 years; groups of 90 male and 90 female mice were
exposed to 625 ppm, 1,3-butadiene on the same schedule. Up to 10
animals from each group were examined after 9 and 15 months of
exposure.
The stop-exposure study consisted of groups of 50 male mice exposed
to 1,3-butadiene at concentrations of 200 ppm for 40 weeks, 625 ppm for
13 weeks, 312 ppm for 52 weeks, or 625 ppm for 26 weeks. After the
exposures were completed, these groups were placed in control chambers
for the remainder of the 2-year study. The total exposure to 1,3-
butadiene (concentration times duration of exposure) in the 13, and 40-
week stop-exposure was approximately 8,000 ppm weeks, while that in the
26- and 52-week stop-exposure groups was approximately 16,000 ppm
weeks.
Previous inhalation studies of 1,3-butadiene in male and female
B6C3F1 mice provided clear evidence of carcinogenicity at exposure
concentrations of 625 or 1,250 ppm. The present inhalation studies--2-
year exposures of 6.25, 20, 62.5, 200, or 625 ppm or shorter duration
exposures of 200, 312, or 625 ppm--provide a better characterization of
the concentration-dependent responses for 1,3-butadiene-induced
neoplasms and nonneoplastic lesions. The present studies confirmed the
clear evidence of carcinogenic activity* of 1,3-butadiene in male
B6C3F1 mice based on increased incidences of neoplasms in the
hematopoietic system, heart, lung, forestomach, liver, harderian gland,
preputial gland, brain, and kidney. There was clear evidence of
carcinogenicity of 1,3-butadiene in female B6C3F1 mice based on
increased incidences of neoplasms in the hematopoietic system, heart,
lung, forestomach, liver, harderian gland, ovary, and mammary gland.
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*The NTP uses five categories of evidence of carcinogenic
activity observed in each animal study: two categories for positive
results (``clear evidence'' and ``some evidence'), one category for
uncertain findings (``equivocal evidence''), one category for no
observable effect (``no evidence''), and one category for studies
that cannot be evaluated because of major flaws (``inadequate
study'').
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Low incidences of intestinal carcinomas in male mice, Zymbal's
gland carcinomas in male and female mice, and renal tubule adenomas and
skin sarcomas in female mice may also have been related to
administration of 1,3-butadiene.
Questions or comments about the Technical Report should be directed
to Central Data Management at P.O. Box 12233, Research Triangle Park,
NC 27709 or telephone (919) 541-3419.
Copies of Toxicology and Carcinogenesis Studies of 1,3-Butadiene
(CAS No. 106-99-0) in B6C3F1 Mice (Inhalation Studies) (TR-434)
are available without charge from Central Data Management, NIEHS, M.D.
A0-01. P.O. Box 12233, Research Triangle Park, NC 27709; telephone
(919) 541-3419.
Dated: July 12, 1994.
Kenneth Olden,
Director, National Toxicology Program.
[FR Doc. 94-17447 Filed 7-18-94; 8:45 am]
BILLING CODE 4140-01-M
