Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 September 2000 to 12 October 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: Grey powder
- Storage conditions: Room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 5 - 7 weeks
- Weight at study initiation: 92 - 115 g
- Fasting period before study: overnight prior to and approximately 4 hours following dosing
- Housing: in groups of three by sex in metal cages with mesh floors
- Diet: Standard laboratory rodent diet ad libitum (Special Diet Services RM1(E) SQC expanded pellet)
- Water: ad libitum
- Acclimation period: 5 days (min.)
- Source: Harlan UK Ltd., Bicester, Oxon, England


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 ºC
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours artificial light (0600 - 1800 hours)

IN-LIFE DATES: From 26 September 2000 to 12 October 2000

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1 % w/v aqueous methylcellulose
Details on oral exposure:
VEHICLE - 1 % w/v aqueous methylcellulose

DOSE VOLUME APPLIED: 10 mL/kg bw

TEST MATERIAL PREPARATION: the test material was formulated at a concentration of 20 % w/v in 1 % w/v aqueous methylcellulose and administered at a volume of 10 mL/kg bw. The test material was prepared on the day of dosing.

The appropriate dose volume of the test material was administered to each rat by oral gavage using a plastic syringe and catheter (8 ch). The day of dosing was designated day 1.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females; 3 males
Control animals:
no
Details on study design:
- Treatment procedure: a group of three fasted female rats received the limit dose. As results at this dosage indicated the acute lethal oral dose to be greater than 2000 mg/kg bodyweight, in compliance with the study guidelines, a group of three fasted males was dosed at 2000 mg/kg to confirm the results and complete the study.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality was checked at least twice daily while animals were observed for clinical signs soon after dosing and at frequent intervals for the remainder of day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day. The nature and severity of the clinical signs and time were recorded at each observation. The bodyweight of each rat was recorded on days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: yes - all animals were killed on day 15 by carbon dioxide asphyxiation and subjected to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
Clinical signs of reaction to treatment were confined to piloerection and hunched posture, seen in all rats, with abnormal gait observed in all females. Recovery of rats, as judged by external appearance and behaviour, was complete by either day 2 (females) or day 3 (males).
Clinical signs are summarised in Table 2.
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
The data is summarised in Table 3.
Gross pathology:
No abnormalities were revealed at the macroscopic examination at study termination on day 15.

Any other information on results incl. tables

Table 2: Signs of Reaction to Treatment

Clinical signs No of rats in groups of 3 showing signs
Male Female
Piloerection 3 3
Hunched posture 3 3
Abnormal gait 0 3

Table 3: Individual Bodyweights and Bodyweight Gains

Dose (mg/kg) Sex Animal No. Bodyweight (g) on day Bodyweight gains (g) on day
1* 8 15 8 15
2000 Male 4 109 185 237 76 52
5 100 164 213 64 49
6 115 184 237 69 53
Mean 108 178 229
Female 1 98 142 166 44 24
2 92 134 157 42 23
3 98 137 160 39 23
Mean 96 138 161

*Prior to dosing

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test accoridng to OECD 423, the acute median lethal oral dose to rats of the test material was demonstrated to be greater than 2000 mg/kg bw. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
Executive summary:

The acute oral toxicity of the test material was determined in accordance with the standardised guidelines OECD 423 and EU Method B.1. During the test, 3 male and 3 female rats received a single oral gavage dose of 2000 mg/kg bw test material, formulated at a concentration of 20 % w/v in 1 % w/v aqueous methylcellulose and administered at a volume of 10 mL/kg bw. During the study, animals were dosed and assessed for signs of toxicity for 14 days following dosing. Bodyweights were recorded at weekly intervals during the study. All animals were killed on day 15 for macroscopic examination post-mortem.

None of the animals died during the study and no significant clinical signs were observed. Furthermore, all animals gained weight during the study and no abnormalities were revealed at the macroscopic examination at study termination on day 15. The acute median lethal oral dose to rats of the test material was therefore demonstrated to be greater than 2000 mg/kg bw.