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EC number: 202-486-1
CAS number: 96-18-4
In the present study (Gulati 1990) the reproductive toxicity of
1,2,3-trichloropropane was tested in a 2 generation study with unique
test design (continuous breeding protocol) where CD-1 Swiss mice were
treated via gavage with 0, 30, 60 and 120 mg/Kg bw in corn oil.
In the parent generation adverse effects on the reproductive
performance, on sex ratio, on pup weight and on reproductive organ
weights were seen at 60 and 120 mg/Kg bw, at which slight signs of
parental toxicity were noted (moderately raised liver and kidney
weights). The effects on reproductive performance was both time and dose
dependent. In the offspring these effects were confirmed but only for
the 120 mg/Kg group, except for effects on estrus cyclicity that were
seen down to 30 mg/Kg bw. The induced toxicity was regarded to slight to
explain the marked adverse effects in both generations. The cross mating
experiment (Task 3) failed to clearly identify the affected sex, though
the data suggests a slightly greater reproductive toxicity for females.
Based on these results 1,2,3 -trichloropropane is deemed a reproductive
toxicant. Due to the limited set of investigations, a clear NOAEL is
difficult to derive. Following a conservative approach based on the
effects on estrous cyclicity in the F1 generation a LOAEL of 30 mg/Kg bw
This assessment is in-line with the evaluation of the Concise
International Chemical Assessment Document 56 on 1,2,3-TRICHLOROPROPANE
(International Program on Chemical Safety (IPCS) 2003,
In the study 4 different Tasks were performed:
Task 1: dose rage finding test
Task 2: treatment of parent generation 7 d during premating and 98 d
during mating (up to 5 consecutive litters)
Task 3: cross over mating of control animals with mice treated at 120
mg/Kg bw to assess the affected sex
Task 4: mating of F0 offspring (= F1) while treated at the same dose as
their respective parents
The following investigations were performed in the respective task:
Task 1 (pretest): 8 per sex and dose, clinical signs (probably daily),
body weight (day1 and day 14), and water consumption (for week 1 and
Task 2 (F0 continuous breeding): 40 control breeding pairs + 20 breeding
pairs per dose, clinical signs of toxicity (probably daily), parental
body weight (probably weekly, values presented for weeks 1, 2, 3, 6, 10,
14), average consumption of water weekly (values presented for weeks
2,6, 10 and 14), fertility (number producing a litter/number of breeding
pairs), litters per pair, live pups per litter, proportion of pups born
alive, sex of live pups and the pup body weights immediately after birth.
Task 3 (F0 cross-over breeding, treated animals only at 120 mg/Kg bw): 3
groups of 20 pairs each: control males x control females, control males
x high-dose females, and control females x high-dose males, same as for
Task 2 + check for copulatory plug + estrual cyclicity as monitored by
vaginal lavage for 12 days preceding necropsy + necropsy (organ weights,
body weight, epididymal sperm motility, sperm morphology and sperm
count) and histopathology (selected organs, results presented for liver,
kidneys, testes, seminal vesicles, prostates, epididymides and ovaries).
Task 4 (F1 breeding): 0, 30, and 60 mg/Kg bw groups 20 breeding pairs,
120 mg/Kg bw group 10 breeding pairs do to low no of live pups in Task 2
in this dose group, same as for Task 2 + check for copulatory plug +
necropsy (organ weights, body weight, epididymal sperm motility, sperm
morphology and sperm count) and histopathology (selected organs, results
presented for liver, kidneys, testes, seminal vesicles, prostates,
epididymides and ovaries).
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