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EC number: 810-258-3
CAS number: -
From the findings of an OECD 422 study, the parental NOAEL for the test animals was considered to be 100 mg/kg/day; however, findings at 500 and 1000 mg/kg/day were confined to salivation, and kidney findings which may be reversible and not relevant in man. The neonatal NOEL was considered to be 500 mg/kg/day. As the parental findings in this study are thought not to be relevant in man, the parental NOAEL for man could be considered to be 1000 mg/kg/day.The above results, which were obtained in test animals that were exposed to the registered substance for approximately 60 days will eventually be combined with those of the on-going OECD 416 study (IUCLID see section 7.8.14. Toxicity to reproduction, Preliminary 2- generation repro study, HF-1000.002, that includes animals dosed for over 100 days. Together this information will provide the necessary data without the need to conduct an additional test in vertebrate animals (the 90-day test). Such data also provide the basis for selecting dose levels for chronic studies (though these results do not warrant the need for such studies) and for establishing safety critera for human exposure to the registered substance as appropriate.
The objective of this study was to assess
the toxicity of the test item in the rat after oral administration. The
study was designed to assess possible effects on reproduction and/or
development. The males were treated for 2 weeks prior to mating, through
to necropsy (ca 4 weeks of treatment). Females were treated for 2 weeks
prior to mating, then through mating, gestation and until at least Day 4
of lactation (ca 6 weeks of treatment). Recovery males and females had a
14 day recovery period prior to termination. The recovery animals were
necropsied and the organ weight and histopathology data were compared to
those of the main study animals.
The animals were monitored daily for any
signs of ill health or reaction to treatment. Detailed functional
observations were performed weekly, with additional functional
observations performed on 5 males and 5 females per group on one
occasion; week 4 for males and during early lactation for females.
Blood samples were also taken from 5 males
and 5 females per group for laboratory investigations. Males were
sampled during week 4 and females were sampled during lactation. In
addition, histopathology was conducted on tissues from 5 males and 5
from Control and High dose groups.
Treatment with HF-1000 was associated with
salivation in animals treated at 500 and 1000 mg/kg/day. The salivation
was generally evident immediately after dosing and was evident up to ca
2 hours post dose and may have been due to an unpleasant taste
associated with the test item.
The type and distribution of neurotoxicity
observations, the haematology parameters and the coagulation and
clinical chemistry parameters did not indicate any association with
At 500 and 1000 mg/kg/day, there was a
statistically significant increase in the kidney weights of the main
study males, however the kidney weights of the recovery males (1000
mg/kg/day) were similar to those of Controls.
Histopathology findings in the male kidneys
(basophilic tubules and hyaline droplets) were noted in main study males
treated at 500 and 1000 mg/kg/day. There were associations between
increased hyaline droplets in the proximal renal tubules, increased
basophilic tubules and the increased kidney weights at these levels. The
findings in recovery males were confined to 2/10 with basophilic tubules
compared to 1 in Controls.
The hyaline droplets that form in the male
rat renal tubules following the administration of materials such as
HF-1000 (volatile hydrocarbon) contain alpha-2microglobulin, and are
unlikely to occur with hydrocarbon administration in man, as little or
none of this protein is present in man, Greaves (2007).
Mating performance and pregnancy performance
were similar across the groups.
At 1000 mg/kg/day, there was an increase in
the number of animals giving birth to dead pups and also in the number
losing more than 3 pups over Days 0-4 of lactation, compared with
Controls. Therefore, for the neonatal toxicity, the Lowest Observed
Adverse Effect Level (LOAEL) was 1000 mg/kg/day and the No Observed
Effect Level (NOEL) was considered to be 500 mg/kg/day.
From the findings on this study, the
parental NOAEL was considered to be 100 mg/kg/day, however, findings at
500 and 1000 mg/kg/day were confined to salivation, and kidney findings
which may be reversible and not relevant in man. The neonatal NOEL was
considered to be 500 mg/kg/day.
As the parental findings in this study are
thought not to be relevant in man, the parental NOAEL for man could be
considered to be1000 mg/kg/day.
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.
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