(I do know that gluteraldehyde has long been known as a carcinogen,
but it appears that benzaldehyde is not (at least that's what *I* read
from this information.  Any chemists out there?)
 
(actually, now that I think about it, I know a chemist at the EPA.
Perhaps I'll drop him an email...)
 
--glen
 
 o / cut along this line
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http://ntp-server.niehs.nih.gov/htdocs/LT-Studies/TR378.html
 
 
TR-378
 
Toxicology and Carcinogenesis Studies of Benzaldehyde (CAS No.
100-52-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies)
 
                                   [Image]
 
                Chemical Formula: C7H6O    -    3D Structure
 
Benzaldehyde is an aromatic aldehyde used in the food, beverage,
pharmaceutical, perfume, soap, and dyestuff industries. Toxicology and
carcinogenesis studies were conducted by administering benzaldehyde
(99% pure) in corn oil by gavage to groups of F344/N rats and B6C3F1
mice of each sex for 16 days, 13 weeks, or 2 years. Genetic toxicology
studies were conducted in Salmonella typhimurium, mouse lymphoma
cells, Chinese hamster ovary (CHO) cells, and Drosophila melanogaster.
 
Sixteen-Day Studies: All rats that received 1,600 mg/kg died by day 2,
and 2/5 males and 2/5 females that received 800 mg/kg died before the
end of the studies. Final mean body weights of dosed and vehicle
control rats were similar, with the exception of the 800 mg/kg groups,
in which males were 14% lighter and females were 11% lighter than
vehicle controls. All mice that received 1,600 or 3,200 mg/kg died by
day 3. Final mean body weights of dosed and vehicle control mice were
similar. No gross lesions attributable to benzaldehyde were detected
upon necropsy.
 
Thirteen-Week Studies: Six of 10 male rats and 3/10 female rats that
received 800 mg/kg and 1/10 female rats that received 400 mg/kg died
near the end of the studies. Final mean body weights of dosed and
vehicle control rats were similar, with the exception of male rats
receiving 800 mg/kg, which were 26% lighter than vehicle controls.
Compound-related lesions seen in rats receiving 800 mg/kg, but not in
those receiving 400 mg/kg, included degeneration and necrosis in the
cerebellum, necrosis in the hippocampus, hyperplasia and/or
hyperkeratosis in the forestomach, and degeneration or necrosis of the
liver and of the tubular epithelium in the kidney.
 
Nine of 10 male mice and 1/10 female mice that received 1,200 mg/kg
benzaldehyde died by the end of the first week. Compound-related renal
tubule degeneration and/or necrosis and reduction in final body weight
were observed in the 600 mg/kg group of male mice. No reductions in
body weight or compound-related lesions were seen in female mice.
 
Based on observations of compound-related lesions involving the brain,
forestomach, kidney, and liver of male and female rats and the kidney
of male mice in the 13-week studies, 2-year studies were conducted by
administering 0, 200, or 400 mg/kg benzaldehyde in corn oil by gavage,
5 days per week for 103 weeks to groups of 50 male and 50 female rats
and for 104 weeks to groups of 50 male mice. Based on survival data
from the 16-day and 13-week studies, groups of 50 female mice were
administered 0, 300, or 600 mg/kg benzaldehyde for 103 weeks.
 
Body Weights and Survival in the Two-Year Studies: Mean body weights
of dosed rats and mice were similar to their respective vehicle
controls throughout the studies. The survival of the high dose group
of male rats was lower than that of the vehicle controls after 1 year;
no other significant differences were observed between any groups of
rats or mice (survival--male rats; vehicle control, 37/50; low dose,
29/50; high dose, 21/50; female rats: 33/50; 33/50; 29/50; male mice:
32/50; 33/50; 31/50, female mice: 30/50; 27/50; 35/50).
 
Nonneoplastic and Neoplastic Effects in the Two-year Studies: The only
effects of benzaldehyde were those seen in the forestomach of mice.
The incidences of uncommonly occurring squamous cell papillomas of the
forestomach in both exposure groups were significantly greater than
those in vehicle controls (male: vehicle control, 1/50; low dose,
2/50; high dose, 5/50; female: 0/50; 5/50; 6/50). The increased
incidences of papillomas were accompanied by dose-related increases in
the incidences in forestomach hyperplasia (male: 7/50; 8/50; 16/50;
female: 12/50; 23/50; 39/50).
 
Genetic Toxicology: Benzaldehyde was not mutagenic in six strains of
S.  typhimurium and did not induce chromosomal aberrations in CHO
cells, with or without exogenous metabolic activation. Benzaldehyde
induced increases in trifluorothymidine-resistant mouse lymphoma cells
in the absence exogenous metabolic activation and increased sister
chromatid exchanges in CHO cells in both the presence and absence of
metabolic activation. Sex-linked recessive lethal mutations were not
induced in the germ cells of adult male D. melanogaster administered
benzaldehyde by feeding or by injection.
 
Conclusions: Under the conditions of these 2-year gavage studies,
there was no evidence of carcinogenic activity of benzaldehyde for
male or female F344/N rats receiving 200 or 400 mg/kg per day. There
was some evidence of carcinogenic activity of benzaldehyde for male or
female B6C3F1 mice, as indicated by increased incidences of squamous
cell papillomas and hyperplasia of the forestomach. Female rats and
male and female mice might have been able to tolerate higher doses.
 
Synonyms: artificial almond oil; artificial essential oil of almond;
benzenecarbonal; benzene carbaldehyde; benzoic aldehyde;
phenylmethanal
 
Pathology Tables, Survival and Growth Curves from NTP 2-year Studies
 
Report Date: March 1990
 
NTIS# PB90-253782/AS