No. 1031 - Miljøstyrelsen

104
CAS no Synonym
Test Exposure
route
556-67-2 D4 dose-response study inhalation,
whole body
556-67-2 D4 subacute toxicity,
pilot study on effects
on liver size and
hepatic enzyme
induction
556-67-2 D4 subacute toxicity,
effects on liver size
and hepatic enzyme
induction
556-67-2 D4 subacute toxicity;
induction of rat hepatic
microsomal
cytochrome P450,
UDPglucoronosyltransferase,
and epoxid
hydrolase
inhalation,
whole body
inhalation,
whole body
inhalation,
whole body
Species / model Conc. Exposure
period
rat (♀), Fisher 344 1, 7, 30, 70, 150,
300, 500, 700 and
900 ppm
6 hours/day; 5
days
rat (♀,♂), Fisher 70 and 700 ppm 28 days, 6
hours/day; 5
days/week
rat (♀,♂), Fisher
344
rat (♀,♂), Fisher
344
556-67-2 D4 subchronic toxicity inhalation albino rat (♀,♂),
Fisher 344, 4
groups, 10 ♀/10 ♂
/ group
556-67-2 D4 subchronic toxicity,
range finding study
for chronic study
inhalation,
nose only
albino rat (♀,♂),
Fisher 344, 4
groups, Gr.2, 3, 4:
20 ♀/20 ♂ /
group; Gr.5: 30
♀/30 ♂ / group
70 and 700 ppm 28 days, 6
hours/day; 5
days/week
70 and 700 ppm 28 days, 6
hours/day; 5
days/week
≤1000 ppm,
repeated dose
(2.78, 5.13, 8.62
and 14.21 mg/l)
≤990 ppm, repeated
dose (0.42,
1.48, 5.91 and
10.87 mg/l)
20 days (♂),
21 days (♀), 6
hours/day; 5
days/week
3 months, 6
hours/day; 5
days/week
Result/Effects NOAEL /
LOAEL
dose-dependent increase in liver size and induction of PROD
activity achieving a max response between 300 and 900 ppm
hepatic conc. of D4 may reach levels saturating CYP2B1/2
activity
induction of CYP2B1/2 enzymes is an early and sensitive
biochemical response to D4 exposure in rat
max can be achieved following 5 days repeated inhalation of
approx. 500 ppm D4
D4 is a Phenobarbital-like inducer of rat hepatic cytochrome
P450 enzymes
dose and time dependent liver enlargement in ♀ rats, maximum
by day 7
induction of several metabolizing enzymes, primarily CYP2B1
D4 induces hepatic cytochrome P450 enzymes
biochemical response similar to phenobarbital
rapid but revesible increase in liver size
induction of several metabolizing enzymes, primarily CYP2B1
D4 induces hepatic cytochrome P450 enzymes
biochemical response similar to phenobarbital
D4 induces CYP enzymes and epoxide hydrolase in a manner
similar to Phenobarbital - i.e. D4 is a PB-like inducer of hepatic
microsomal enzymes in the Fisher 344 rat.
reduced food consumption
reduced body weight and body weight gain
thymic atrophy
vaginal mucification
reduction in corpora lutea score
slight reduction in body weight and food intake at 990 ppm.
slight dose related increase in abs. and rel. liver weight (♀
most sensitive)
slight reduction in thymus and ovarian weight in ♀ at the
highest 2 doses
ovarian atrophy and vaginal mucification in ♀ at 990 ppm
EPA DCN/Ref.
no data 86990000029
1999
no data 86970000723
1996
no data 86970000725
1997
no data McKim JM et al
1997
no data 86950000155
1995
no data 86950000153
1995