Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 Feb - 04 Mar 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

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 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF Japanese test guidelines (2000)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Alpha-Chloro C-6 Monomer
- Physical state: colourless liquid
- Expiration date of the lot/batch: 2004-08-31
- Stability under storage conditions: stable
- Storage condition of test material: in refrigerator in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 10-11 weeks
- Weight at study initiation: 220-255 g
- Fasting period before study: food was withheld overnight (for a maximum of 20 h) prior to dosing until 3-4 h after administration of the test substance
- Housing: group housing of 3 animals per sex and cage in labelled Macrolon cages (type IV, height 18 cm) containing purified sawdust as bedding material (Woody-Clean type 3/4; Tecnilab-BMI BV, Someren, The Netherlands)
- Diet: standard pelleted laboratory animal diet (Altromin VRF 1, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 +/- 3.0
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: From 2004-02-12 To 2004-03-04

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DOSE VOLUME APPLIED:
2000 mg/kg bw: 1.3 mL/kg bw
300 mg/kg bw: 0.19 mL/kg bw
dose volume calculated as dose level according to specific gravity

CLASS METHOD (if applicable)
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg bw. The absence or presence of mortality of aminals dosed at one step determined the next step, based on the procedure defined in the test guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
Doses:
2000 mg/kg bw
300 mg/kg bw
No. of animals per sex per dose:
3 females per step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were weighed on Day 1 (prior to the administration) and on Days 8 and 15. A careful clinical examination was made several times on the day of dosing. Thereafter, animals were observed for clinical signs once daily until the end of the 14-day observation period.
- Necropsy of survivors performed: yes

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 experimental
Sex:
female
Dose descriptor:
LD50
Effect level:
1 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut-off according to OECD 423
Mortality:
Step 1 – 2000 mg/kg bw: 2/3 females died (both 4 h after tratment)
Step 2 – 300 mg/kg bw: 0/3 females died
Step 3 – 300 mg/kg bw: 0/3 females died
Clinical signs:
2000 mg/kg bw: Lethargy, hunched posture, uncoordinated movements, slow breathing, shallow respiration, piloerection, hypothermia and/or ptosis (all females). The surviving animal had recovered from the symptoms on day 5.
300 mg/kg bw: Hunched posture on days 1 and/or 2 (all females).
Body weight:
A slightly low body weight gain was noted for one female at 300 mg/kg bw between days 8 and 15.
The body weight gain shown by the other surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

Table 1. Clinical signs and mortality

Step

Dose
[mg/kg bw]

Toxicological results*

1

2000

2/3/3

2

300

0/3/3

3

300

0/3/3

 * first number = number of dead animals

 second number = number of animals with clinical signs

 third number = number of animals used

         

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: Acute Tox. 4., H302
DSD: Xn, R22