α-chloro-o-xylene

Acute Toxicity: oral

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Adopted 12 May 1981

Deviations:

no

Test guideline 2

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

Test material information

Constituent 1

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 levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

775 mg/kg bw

Based on:

test mat.

95% CL:

>= 555 - <= 893

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

697 mg/kg bw

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

> 800 - < 900 mg/kg bw

Based on:

test mat.

Effect levels 4

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.