Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Oct 22 1986 - Nov 17 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
conducted according to GLP, but no information on test substance characterization available

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Adopted 12 May 1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
Guideline of the Commission 25 April 1984
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
α-chloro-o-xylene
EC Number:
209-013-8
EC Name:
α-chloro-o-xylene
Cas Number:
552-45-4
Molecular formula:
C8H9Cl
IUPAC Name:
1-(chloromethyl)-2-methylbenzene
Test material form:
liquid
Specific details on test material used for the study:
clear, yellow fluid
ca. 99% pure

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoeachst AG, Kastengrund, SPF-Zucht
- Age at study initiation: males 7 weeks, females 8 weeks
- Weight at study initiation: males 187 g (± 10 g), females 182 g (± 7g)
- Fasting period before study: ca. 16 hours before and 3-4 hours after application
- Housing: macrocolon cages (Type 4) in groups of 5
- Diet (e.g. ad libitum): ad libitum, Rat diet Altromin 1324 (Altromin-GmbH, Lage/Lippe)
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): no information
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sesame oil (Oleum Sesami Ph.Euri.III, Fa. Mainland Pharmazeutische Fabrik GmbH, Ffm.)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 6.3, 8.0, 9.0, 10.0 % to achieve 630, 800, 900, and 1000 mg/kg bw, respectively

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:
Based on previous dose-finding experiments, the following doses were tested:
630, 800, 900, 1000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations at least daily, weighings were conducted weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
LD50, 95% confidence were calculated using probit analysis

Results and discussion

Preliminary study:
Application of 100, 3150, and 5000 mg/kg bw test substance to one male and one female each. All animals but one male in the 1000 mg/kg bw dose level group died. Clinical signs included cowering position, decreased spontaneous activity, ruffled fur, irregular breathing, salivation, narrowed eyelids, diarrhea, drawn-in flanks, hyperemia, unccordinated and remarkable gait. Additionally, females of the 1000 and 3150 mg/kg groups showed decreased reflexes, depressed breathing rates, staggering, and crawling.
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
775 mg/kg bw
Based on:
test mat.
95% CL:
>= 555 - <= 893
Sex:
female
Dose descriptor:
LD50
Effect level:
697 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
> 800 - < 900 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 630 - < 800 mg/kg bw
Based on:
test mat.
Clinical signs:
other: Males and females of all dose levels showed the following symptoms starting the day of application: reduced spontaneous activity, cowering position, drawn-in flanks, uncoordinated and remarkable gait, irregular breathing, ruffled fur, narrowed eyelids, di
Gross pathology:
deceased animals:
- liver: bright spots, yellow beige spots
- lungs: blood
- stomach: petechial bleeding in the stomach wall
- small intestine: yellow-beige discoloration
- pancreas: reddened

surviving animals:
no macroscopic changes observed

Any other information on results incl. tables

Mortalities:

dose

[mg/kg bw]

male animals

female animals

absolute

relative [%]

absolute

relative [%]

630

1 / 5

20

1 / 5

20

800

1 / 5

20

5 / 5

100

900

5 / 5

100

-

-

1000

5 / 5

100

4 / 5

80

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the effects observed and laying down the criteria specified in Regulation (EC) 1272/2008 (CLP), classification as harmful if swallowed (H302) is warranted.