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EC number: 201-152-2
CAS number: 78-87-5
repeat dose toxicity of 1,2-dichloropropane has been investigated
extensively by NTP (1986) in a series of GLP-compliant studies using
male and female F344 rats and B6C3F1 mice. Key aspects of the design of
these studies, along with the main findings, are summarized in Table
3.1.5. The results indicate that the liver is a target organ after
gavage administration, with a chronic NOAEL of 125 mg/kg bw/day in
female rats (males unaffected) and a chronic LOAEL of 125 mg/kg bw/day
in male mice (females unaffected). Acanthosis of the stomach (indicative
of persistent local irritation) was noted in mice (rats unaffected) with
a chronic NOEL of 125 mg/kg bw/d in males and a chronic LOEL of 125
mg/kg bw/d in females. Body weight was decreased 14-24% in rats (chronic
NOELmales = 62 mg/kg bw/d, chronic NOEL females = 125 mg/kg bw/d)
whereas mice were unaffected (chronic NOEL = 250 mg/kg bw/d, both
sexes). The overall NOAEL values following chronic administration of PDC
were 62 and 125 m/kg bw/d for male and female rats respectively.
No chronic NOAEL was derived for mice of either sex; the LOAEL was 125
neurological consequences of repeated oral exposure to
1,2-dichloropropane have been investigated in F344 rats (n =
15/sex/group) given 0 (corn oil), 20, 65 or 200 mg/kg bw/day for 13
weeks by gavage (Johnson and Gorzinski, 1988). The study followed U.S.
E.P.A. guidelines and was conducted to the standards of GLP. Prior to
treatment, and at monthly intervals during the study, all animals were
assessed for a number of endpoints including functional observational
battery, hindlimb grip strength, and motor activity. After a 13-week
treatment, 4 rats/sex/dose were randomly selected for terminal
examination (including histopathological examination of brain, spinal
cord and nerve) while the remainder were retained (no further treatment)
for a 9 week recovery period. Transient clinical signs (lacrimation,
blinking, and decreased spontaneous motor activity) were reported on
days 3-4 of treatment, and body weight was slightly decreased at week 13
in both sexes. There were no effects attributable to 1,2-dichloropropane
in the functional observational battery, grip strength, or motor
activity. Results from the gross and microscopic examination of the
brain and nervous system revealed no treatment-related lesions.
apart from a minor effect on body weight (NOAELmales=
20 mg/kg bw/day; NOAELfemales
mg/kg bw/day), no adverse structural or functional neurological
consequences were apparent in rats following 13 weeks gavage
administration of 1,2-dichloropropane at doses up to 200 mg/kg bw/day.
conclusion, results from repeat dose studies indicate that theliveris
a target organ in rodents with a chronic oral NOAEL of 62 -125 mg/kg
bw/d in rats and a chronic LOAEL of 125 mg/kg bw/d in mice (no NOAEL
established). There were no adverse systemic organ effects in rats and
mice following sub-chronic exposure to 150 ppm 1,2-dichloropropane
(NOAEL), whereas red blood cell parameters (regenerative anemia) were
altered in rabbits with a LOAEL of 150 ppm in males and a NOAEL of 150
ppm in females. Body weight was slightly but statistically significantly
decreased in rats only (NOAEL 15 ppm) in these sub-chronic inhalation
studies, with site-of contact (irritative) changes present in stomach
(mouse, NOAEL/LOAEL 125 mg/kg bw/d after oral gavage, dependent on sex)
and nasal tissue (rat, NOAEL 15 ppm after inhalation; rabbits, NOAEL 500
NOAEL: 62 mg/kg bw is
the lowest value among all available studies
Results of repeated toxicity studies did not
lead to the classification of 1,2-dichloropropane for long term effects.
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