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: 257-856-5 | CAS number: 52334-81-3
The overall mean values (with standard deviations) were as follows:
Low level 0.27 ± 0.14 mg/l
Middle level 0.95 ± 0.16 mg/l
High level 3.87 ± 0.30 mg/l
It was found that it was difficult to keep constant the concentration of the high exposure level: the same flowmeter settings gave apparently different concentrations on different days and there were also frequently considerable variations within a given day. It should also be noted that the animals of groups 2 and 3 (batches C and D only) were inadvertently transposed prior to exposure on day 34 and were therefore exposed to mean concentrations of 0.95 and 0.24mg/l respectively.
General effects: during exposure, it was generally noted that animals in groups 1-3 were normal but that signs of eye and nasal irritation were seen in animals exposed to 4.0mg/l. These animals appeared to be slightly worse during their first day of exposure, but on most days similar observations were made i.e. they were restless, their eyes were partially closed, they had salivation and/or nasal discharge, they were often rubbing at their eyes and noses and grooming themselves or each other, although having a poorly groomed appearance. Tremors were also seen in some animals. The absorbent tray paper under the exposure chambers was wetter for the 4.0mg/l group than for the other groups, suggesting increase urination. The results of the more detailed clinical examinations carried out after exposure are described below but it was noted when returning animals to their cages after exposure that, especially at the top dose, they were wet, ill-groomed and had piloerection. They were also frequently hunched, subdued, vocalised when handled and had tail erection. A few animals exposed to 1.0mg/l were affected especially in the earlier stages of the experiment. The controls and animals exposed to 0.25mg/l appeared normal apart from male 439 which was noted to have partial paralysis of the hind limbs after its first exposure. It was subsequently found that the left limb only was affected and persisted for a further three days. On the first exposure of batch B animals, one animal exposed to 0.25mg/l (which included male 439) had bee trapped in the exposure chamber but it had not been possible to identify it when it was released. It was probable, however, that it was male 439. One animal, male 505 (group 4 batch C) was found dead after its first exposure.
In all groups CTF produced symptoms consistent with effects on both the central and autonomic nervous systems, which persisted after exposure had ended. Although dose related, the clinical effects were minimal in the group exposed to 0.25mg/l. The autonomic effects were consistent with both androgenic and cholinergic stimulation, but it is unlikely that CTF works post synaptically in both cholinergic and androgenic nerves. A more likely explanation is that its action is on ganglia or on the higher nervous system probably by false transmissions or mediator release. The effects of CTF on the central nervous system in this study suggest an anaesthetic or depressive action.
Weigh gains of animals exposed to 0.25mg/l and 1.0mg/l were comparable with those of the control group. Males and females exposed to 4.0mg/l, however, lost weight after two exposures although at the end of the exposure period, body weights of the females were similar to those of the other groups. Weight gain in males was reduced although was comparable with that in the other groups during the second week of the recovery period.
Food consumption was reduced for males exposed to 4.0mg/l during the whole of the exposure period but was comparable with the control group during the recovery period (although measured for one cage of animals only). Food consumption for females exposed to 4.0mg/l was reduced during the first week of exposure but was similar to that of the controls during the rest of the exposure period and was apparently increased during the recovery period. No correction has been made for those animals of groups 2 and 3 which were housed in each other’s cages during a three day period.
Food utilisation during the exposure period showed no reduction in efficiency in the treated groups compared with the controls.
A statistically significant difference was found between the control group and the test group means at 28 days for the following parameters:
a) Haemoglobin. The mean haemoglobin level was slightly reduced in the females exposed to 4.0mg/l.
b) Red cell count. The mean red cell count was slightly reduced in the females exposed to 4.0mg/l.
c) Mean cell haemoglobin concentration. MCHC was slightly reduced in all the female test groups but only at the top dose mean was significantly lower than the control.
d) Lymphocyte count. The mean lymphocyte count was increased in the females exposed to 1.0mg/l. In addition, kaolin-cephalin time was slightly reduced in all female groups but was not statistically significant.
The majority of the above changes were sporadic and even where all test groups were affected (MCHC, female) the change was too small to be of haematological significance.
a) Terminal. There were slight decreases in the glucose levels of the males and females exposed to 4.0mg/l. There were also increases in cholesterol levels of males and females exposed to 4.0mg/l and of females exposed to 1.0mg/l with associated increases in triglyceride levels of males and females exposed to 4.0mg/l. No other effects were observed.
b) Seven-day recovery. No difference between control and treated groups were seen.
a) Terminal. There was a small decrease in the volume excreted together with an increase in specific gravity of the females exposed to 4.0mg/l. A dose-related decrease in pH was seen in females exposed to 1.0 and 4.0mg/l. All male treated groups had some evidence of ketones present. The protein level of the males exposed to 4.0mg/l was slightly lower than that of the other groups.
b) Seven day recovery. The protein level of the males which had been exposed to 4.0mg/l was still lower than that of the other group and there was still some evidence of ketones present in males which had been exposed to 1.0 and 4.0mg/l and females which had been exposed to 4.0mg/l.
Macroscopic Findings: The male exposed to 4.0mg/l (no. 505) which was found dead had froth in its trachea and an ulcer in the pyloric region of the stomach (described as depressed area in mucosa, entire surface of pyloric region irregular and altered blood present in the ileum). There were no other findings related to treatment either at the end of the exposure or recovery period.
At the end of the exposure period, liver, kidneys, and adrenals showed statistically significant increases in both organ weights and organ/bodyweight ratios. These were usually found in both sexes and appeared to be dose-related. In addition, spleen weights were decreased. At the end of the recovery period there were isolated statistically significant differences but all except for the heart in females exposed to 4.0mg/l were decreases. There appeared, therefore, not to be any relationship with the changes found at the end of the recovery period and those found at the end of the exposure period.
The main target organ was the liver. After four weeks exposure to 4.0mg/l, most animals showed mild diffuse hepatic degeneration in the form of granular eosinophilic cytoplasm of hepatocytes, displacement of basophilic granules, swollen hepatocytes and apparent increase in mitotic figures in both sexes. In addition, increased fatty vacuolation occurred in females. Half of the animals exposed to 1.0mg/l showed hepatic degenerative lesions similar to those seen in animals exposed to 4.0mg/l but the changes were mainly focal. Almost half showed slight fatty vacuolation. Of the animals exposed to 0.25mg/l, three only showed focal hepatic degeneration. Almost half showed slight fatty vacuolation. No hepatic degeneration was seen in the control rats but some livers showed slight fatty vacuolation.
After a two week recovery period, half the rats previously exposed to 4.0 mg/l showed focal to diffuse hepatic degenerative lesions and only one male showed moderate fatter vacuolation. Almost half the livers from the middle exposure group showed focal hepatic degenerative lesions and half the male livers showed slight fatty vacuolation. All the livers from the group 2 animals appear to the normal in both sexes.
No degenerative lesions were seen in the controls and only one male rat showed slight fatty vacuolation.
Hepatocyte degeneration was still apparent in some animals in groups 3 and 4. The livers of the group 2 rats were within normal limits.
In addition more that half the animals exposed to 4.0mg/l showed a mild degree of tracheitis while the controls showed no such lesion. Although there were no other treatment-related effects, there was peribronchial lymphocyte infiltration in almost all controls and in animals exposed to 4.0mg/l, which was attributed to a virus infection. The animal that died at the end of its third exposure (male 505, group 4) had acute gastritis and duodenitis but these findings were considered not to be dose related.
Groups of 16 male and 16 female rats were exposed for six hours a day, five days a week for four weeks to 0, 0.25, 1.0, 4.0mg/l (0, 33, 132 or 529ppm) 2-chloro-5-trifluoromethyl pyridine (CTF). The atmospheric concentration of CTF was monitored by infra-red spectroscopy.
The animals were observed during and after exposure and were given detailed clinical observations at intervals during the experiment. Bodyweight and food consumption were measured regularly. Urine samples were taken terminally. The day following the last exposure, 12 males and 12 females per group were killed and, after cardiac blood samples had been taken for clinical chemistry and haematology, each animal was given a post mortem examination. Selected organs were weighed and samples of tissues preserved for histopathological examination. The remaining 4 males and 4 females per group were retained for a two week recovery period. After one week of this period, tail vein blood samples and urine samples were taken for clinical chemistry. At the end of the recovery period, the animals were killed and subjected to a post mortem examination during which again organs were weighed and tissues take for histopathology.
It was found that there were dose-related clinical abnormalities consistent with effects on the central and autonomic nervous systems and, at the top exposure level, irritant effects on mucous membranes. Bodyweight gain was reduced in the animals exposed to 4.0mg/l, particularly in males, and was associated with reduced food consumption. There were no haematological effects but there were biochemical ones, the major changes being an increase in triglyceride and cholesterol levels in the high exposure group and a slight increase in ALT activity in the females of this group.
At post mortem examination, liver weights showed a dose-related increase. Histologically, the livers showed dose-related degenerative changes (without necrosis) which became more diffuse as the dose increased, and fatty vacuolation which similarly became less marked with decreasing dose. Adrenal and kidney weights were also increased at the top dose and mild tracheitis was seen histologically. All effects recovered in the 0.25mg/l group and recovered or showed signs of recovery at higher levels.
It is concluded that CTF is irritant to mucous membranes at high levels, affects the nervous system and is also toxic specifically to the liver, although not severely so at the exposure levels tested. Although there is no true ‘no effect’ level in this study, the 0.25mg/l level is considered to be a minimal effect level.
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.
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.
Close Do not show this message again