Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: granular
Remarks:
Granular white powder
Details on test material:
Granular white powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Male and female Sprague-Dawley CD Wit CD" (SD) kiS BR-) strain rats were supplied by
Charles River (UK) Ltd. Margate. Kent, UK. On receipt the animals were randomly allocated to
cages. The females were nulliparous and non-pregnant. After an aclimatisation period of at least
flve days the animals were selected at random and given a number unique within the study by
indelible ink-marking on the tail and a number written on a cage card. At the start of the study the
animals weighed at least 200g and were approximately eight weeks of age.
The animals were housed in groups of three by sex in solid-floor polypropylene cages furnished
with woodflakes. With the exception or an overnight fast immediately before dosing and for
approximately two to four hours after dosing; free access to mains drinking Nvater and lud (Rat
and Mouse Expanded Diet No.1, Special Diets Services Limited. Witham, Essex. UK) was
allowed throughout the study. The diet. drinking water and bedding were routinely analysed and
were considered not to contain any contaminants that would reasonably he expected to affect the
purpose or integrity of the stub...
The temperature and relative humidity were set to achieve limits of 19 to 25"C and 30 to 70%
respectively. Any occasional deviations from these targets were considered not to have affected
the purpose or integrity of the study.The rate of air exchange was at least fifteen changes per
hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00
to 18,00) and twelve hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
All animals were dosed once only by gavage. usinv a metal cannula attached to a
graduated syringe. The volume administered to each animal was calculated according to the
fasted bodyweight at the time of dosing. Treatment of animais was sequential. Sufficient time
was allowed between each sex to confirm the survival of the previously dosed animals.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
three
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing
and subsequently once daily for fourteen days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
N/A

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths
Clinical signs:
I lunched posture and lethargy were noted in females two to four hours after dosing with hunched
posture noted one day after dosing. An isolated incident of emaciation was noted in one female
on Day 8 of the study . The males showed no signs of systemic toxicity.
Body weight:
All animals showed expected gains in hodyweight over the study period except for one female
which showed a bodyweight loss during the first week hut expected gain during the second week
or 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 oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD (Cri:
CD (SD) I(iS BR) strain rat was estimated as being greater than 2000 mg/kg bodyweight.
The test material does not meet the criteria for classification according to EU labelling regulations
Commission Directive 93/21/EEC, and subsequently Commission Regulation 1272/2008/EC
Executive summary:

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD { Cri: (SD} 1G HR t strain rat. The method was designed to meet the requirements of the following: • OECD Guidelines for the Testing of Chemicals No, 423 "Acute Oral Toxicitv - Acute Toxic Class Method - (adopted 22 March 1996.} • Commission Directive 96754/EC Method 131 tris Acute Toxicity (Oral) - Acute Toxic Class Method.

A group of three fasted females was treated with the test material at a dose level of 2000 mg/kg bodyweight. This was followed by a group of three fasted animals of the other sex at the same dose level.

The test material was administered orally as a suspension in arachis oil BP. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths.

Signs of systemic toxicity noted in females were hunched posture. lethargy and an isolated incident of emaciation. The males showed no signs of systemic toxicity.

All animals showed expected gains in bodyweight over the study period except for one female which showed a hodyweight loss during the first week but expected gain during the second week of the study.

No abnormalities were noted at necropsy

Conclusion. The acute oral median lethal dose (1.1) 5 0 of the test material in the Sprague-Dawley CD (Crl: CD (SD) IGS BR) strain rat was estimated as being greater than 2000 mg/kg bodyweight. The test material does not meet the criteria for classification according to EU labelling regulations Commission Directive 93/21/EEC and subsequently Commission Regulation 1272/2008/EC.