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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Jun 2006 to Oct 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Sponsor batch no: 151105Purity: 99.9%

Test animals

Species:
rat
Strain:
other: Crl:WI(Han)
Sex:
female
Details on test animals and environmental conditions:
Female (nulliparous, non-pregnant) rats of the Crl:Wl(Han) strain were obtained from Charles River UK Ltd, Margate. All animals were given a clinical inspection for ill health on arrival and a samp le was weighed. Rats were arbitrarily selected from the delivery boxes and allocated to the appropriate number of cages using a sequence that reduced selective bias. Groups of fasted animals were treated as follows: Dose Level (mg/kg) Concentration(mg/lmL) Dose Volume ml/kg) Number of Animals 2000 200 10 3 2000 200 10 3Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals. The Study Director selected the starting dose level that was considered to be most likely cause the deaths of one or two animals. Once the treatment-re\at ed mortality caused by the first dosing regime was established, the regime appropriate for a second group of three rats was read from a flow diagram. Successive groups of rats were treated according to the mortality affecting the previous treated group until the flow diagram indicated that the Globally Harmonised Classification System (GHS) could be applied to the test article.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
1% aqueous methyl cellulose
Details on oral exposure:
Doses were administered orally, by gavage using plastic syringes and rubber catheters. Each rat was dosed once on Day 1, by passing the tip or a catheter along the oesophagus and instilling the test article into the gastric lumen.
Doses:
The dose volume was 10 mL/kg.
No. of animals per sex per dose:
3 per dose
Control animals:
no
Details on study design:
Dose levels were expressed gravimetrically and in terms of test article received (without regard to purity or active content). Individual doses (mL) were calculated using the fasted body weights of the rats on the morning of dosing (Day 1) and the dose volume of 10 mL/kg. The condition of the animals was assessed daily throughout the acclimatisation period of 7 to 9 days . A second inspection was performed prior to study commencement to ensure the animals were suitable for the study. Overtly healthy animals were arbitrarily allocated to the study groups at least one day prior to dosing. A number written on the tail in indelible ink on the day before dosing individually identified the rats. A colour-coded card on each cage gave information including study number, group number, animal numbers and sex.At the start of the study the rats were 8 to 9 weeks of age. The weight variation did not exceed ±20% of the mean weight.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels: Piloerection was observed in all three animals in the first group at 2,3 and 4 hours post-dose. No other clinical signs were noted.
Body weight:
All rats achieved bodyweight gains during the first and second weeks of the study
Gross pathology:
No abnormalities were noted at necropsy

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute median lethal oral dose level of the test article, Beta Ketosulflde, was found to exceed 2000 mg/kg.
Executive summary:

This study was conducted in compliance with Method B1 tris of Commission Directive 2004/73/EC and OECD Guidelines for Testing of Chemicals, Method 423 (adopted 17 Dec 2001).

This study was conducted to assess the acute toxicity of the test article, BetaKetosulfide following a single oral administration to small groups of rats. The study design provides information for hazard assessmentand classification and enables a chemical to be assigned to toxicity classes but severely restricts animal usage.

Groups of three female fasted rats were given the test article as a single dose on Day1 by oral gavage at a dose level of 2000mg/kg. The test article was dispersed in 1% aqueous methyl cellulose and administered at a dose volume of10mg/kg. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths following a single oral dose of Beta Ketosulfide among rats dosed at 2000mg/kg. Piloerection was observed in all three animals in the first group at 2,3 and 4 hours post dose. No other clinical signs were noted.

All rats achieved body weight gains during the first and second weeks of the study. No abnormalities  were  noted  at  necrospsy.  The  acute  median  lethal  oral  dose  level  of  the test article, BetaKetosulfide, was found to exceed 2000mg/kg.