Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 202-486-1
CAS number: 96-18-4
- Table 1: Final body weights of rats after subacute and subchronic
exposure to 1,2,3 -trichloropropane
Body weight (g) after 10-day exposure
Body weight (g) after 90-day exposure
451 ± 8
529 ± 13
410 ± 13
528 ± 16
436 ± 7
509 .±. 11
417 ± 8
533 ± 16
337 ± 12*
426 ± 13*
253 ± 4
301 ± 5
256 ± 3
301 ± 9
262 ± 4
307 ± 10
260 ± 3
301 ± 6
195 ± 6*
258 ± 7*
Body weights were measured on the day of sacrifice. Values represent
means ± SEM for 10 rats per group. An asterisk indicates means that are
significantly different from the control value at P < 0.05.
- Table 2: Incidence of organ histopathology of rats after subacute and
subchronic exposure to 1,2,3 -trichloropropane
mmol/kg/day x 10 days
mmol/kg/day x 90 days
Mandibular lymph node
Tissues were prepared for histological evaluation by staining with
hematoxylin and eosin. Tissues of 10 animals were evaluated for each
dose group unless otherwise indicated. A dash means that the tissues
were not evaluated.
In the present study (Merrick 1991) the toxicity of
1,2,3-trichloropropane was tested in Sprague Dawley rats in a 90 d
repeated dose study with oral treatment via gavage (5 d/wk) according to
OECD TG 408. Results for a 10 d dose range finding experiment are
A NOAEL could not be derived from the reported results as a raised
prevalence of inflammation-associated diffuse necrosis of the cardiac
myocardium was seen in all dose groups of the 90 d experiment but with
an uncommon dose response pattern.
Animals aged 80 d at study initiation were treated with 1,2,3
-trichloropropane in corn oil, weighted weekly and their water
consumption was determined twice weekly. At terminal sacrifice blood
samples were taken for clinical chemical analysis and hematology. These
animals were subjected to gross necroscopy and full histological
No mortalities and adverse clinical signs were reported. Reduced body
weight gain was found in the males and females of the high dose groups
both in the 10 d and the 90 d study. No treatment related effects were
seen regarding water consumption of treated animals as compared to
controls. Hematologic examination revealed a slightly reduced white
blood cell count in males after the 10-day exposure but no such effect
in females or any of the dose groups in the 90 d study, therefore this
finding is regarded as incidental. For the 10 d study: significantly
increased ALT and AST values at the high dose are reported. Accordingly
also in the 90 d study significantly raised ALT and AST levels at the
high dose in female rats only were determined. Raised values in males of
the 90 d study were compromised by very high ALT and AST levels in male
controls, mirrored by histopathological findings in this control group.
Several absolute organ weights are reduced (heart, spleen, thymus and
lung) in the high doses of both sexes of both studies but as the body
weights are reduced in these groups the more relevant relative organ
weights of heart, lung and spleen (and ovaries in females) showed
generally no differences. Nevertheless the relative thymus weight was
decreased in the high dose groups of both sexes in the 10 d study (but
not in the 90 d study) and generally raised relative liver and kidney
weights in the two highest doses groups in both sexes in both studies
were reported. Effects in the relative brain weights were explained by
the reduced body weights in the high dose groups.
Several non-neoplastic lesions were revealed by the histologic
examination, the most prominent being found in the heart as diffuse
inflammation-associated necrosis of cardiac myocardiumin both sexes in
all treatment groups in the 90 d study but only in the high dose group
in the 10 d study. The prevalence for males was higher then for females
and there is no clear dose response to this effect. The severity of
cardiac lesions is reported to increase dose dependently (no detailed
values given). This cardiac lesions were reported by the authors to
occur also in Long Evans rats and F344 rats if treated for 10 d at 0.8
mmol/Kg bw/d (high dose of the 10 d study).
In thymus atrophy in the high doses groups of both sexes in the 10 d
study is reported, but no effects in the 90 d study, therefore this
effect is not regarded as adverse. For the liver mild centrilubolar
hepatic necrosis in one female and two males of the high dose was
detected in the 10 d study. In the 90 d study in females minimal liver
necrosis in one animal in the 0.05 mmol/Kg dose group and in two animals
of the high dose group was found while in males mild to moderate liver
necrosis with increasing dose related incidence (1 - 4) in the
respective dose groups was detected. The latter findings were confounded
by mild hepatic lesions in four of the male control animals.
Several indications for preneoplastic lesions were also noted as there
are an increased prevalence of bile duct hyperplasia in both sexes in
the high dose group in the 90 d study, plasma cell hyperplasia in the
mandibular lymph nodes at variable extent in control males and females,
but increased incidence in males exposed to high dose after 10 days plus
in the 90 d study a dose dependently increased prevalence of mandibular
lymph node hyperplasia.
Other proliferative and neoplastic lesions in individual animals at high
dose treatment comprised broncho-alveolar adenoma in a male, an
adenocarcinoma of a female mammary gland, a forestomach squamous cell
papilloma in a male and forestomach squamous cell hyperplasia in a male.
No lesions in mesenteric, subcutis, pancreatic, bronchiolar or
mediastinal lymph nodes subchronic exposure conditions.
A derivation of a NOAEL or a LOAEL is not possible for the 90 d study.
All adverse effects occur at the highest dose with two exceptions.
Firstly relative weight effects in the liver and liver enzyme effects
are seen also at the second highest dose (0.1 mmol/Kg/d = 14.74 mg/Kg/d)
but these effects are confounded by a uncommon mild liver necrosis in 4
of the control animals. Secondly a significant prevalence of
inflammation-related degeneration and necrosis of cardiac myocardium was
seen in males of the high dose and to a lesser extent in the females of
this dose level. In both sexes there is no clear dose response: 3/10
males showing inflammation at 0.01 mmol/Kg/d, 2/10 at 0.05, 3/10 at 0.1
and 8/10 at 0.4. The respective prevalences for females are 1/10, 2/10,
1/10 and 8/10.
Prevalences of degeneration and necrosis show a comparable variability.
Using the concept of LOAEL and NOAEL strictly would imply a to set the
LOAEL for this study to the lowest dose (0.01 mmol/Kg/d = 1.47 mg/Kg
bw/d). Nevertheless the complete absence of cardiac effects in a 120 d
gavage study and even a 2 year chronic gavage study at comparable dose
levels (see chapter 7.5.1: Hazleton (1983) / key (120d study on F344
rats) (8 - 250 mg/Kg bw/d) and chapter 7.7: National Toxicology Program
(1993) / Rat and Mouse (3 - 30 and 6 - 60 mg/Kg bw/d, respectively))
renders the correlation between the cardiopathic effects and the 1,2,3
-trichloropropane exposition questionable.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Deze website maakt gebruik van cookies om het surfen zo aangenaam mogelijk te maken.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again