Reaction mass of m-cresol and 2-chloro-m-cresol and 6-chloro-m-cresol

Acute Toxicity: oral

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:

other: GLP compliant OECD 423 guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(2001)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

2009-02-09, North Rhine-westphalia

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Preventol KMX

IUPAC Name:

Preventol KMX

Details on test material:

- Name of test material (as cited in study report): Preventol KMX
- Physical state: colorless liquid
- Analytical purity: 100%
- Lot/batch No.: CHK 2109
- Expiration date of the lot/batch: 2011-09-21
- Stability under test conditions: Ensured by the sponsor
- Storage condition of test material: At room temperature due to product information by the sponsor

Test animals

Species:

rat

Strain:

other: Wistar HsdCpb:Wu

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan GmbH, 5960 AD Horts, Netherlands
- Age at study initiation: approx. 8 - 12 weeks (assumed by the body weight)
- Weight at study initiation: 156 g - 174 g
- Housing: grouped
- Diet: Provimi Kliba 3883 PM S15 Maus/Ratte Haltung, Kaiseraugust Switzerland; ad libitum, except for the day before administration of the test substance. Food was withheld from the animals for 16- 24 h before and 2-4 h after administration of the test substance.
- Water: tap water; ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 55 ± 5%
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG400

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 females at 2000 mg/kg bw
2x3 females at 300 mg/kg bw

Control animals:

no

Details on study design:

- Starting dose: 2000 mg/kg bw
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs and mortality were determined several times at the day of application (defined as day 1) and at least once daily thereafter. The weight gain was checked weekly.
Animals which died or were sacrificed in a moribund state were weighed and subjected to gross pathology
- Necropsy of survivors performed: yes

Statistics:

A validated LAN-linked computer system was used for data collection, processing and evaluation.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2/3 animals of the high dose group died during the observation period.
No mortalities occured at 300 mg/kg bw.

Clinical signs:

Clinical signs at 2000 mg/kg bw comprised of: decreased motility, lateral position, abdominal position, tremor, narrowed palpebral fissure, piloerection and labored breathing.
No clinical signs were observed in animals of the 300 mg/kg bw dose group.

Body weight:

No significant effects on body weight or body weight gain were noted.

Gross pathology:

Gross pathology of the two animals which died during the observation period revealed dilated intestine/stomach (gas filled). The animal of the high dose group sacrificed at study termination showed a spotted lung.
No gross pathological changes were noticed in any animal treated with 300 mg/kg bw.

Any other information on results incl. tables

Table 1: Table for acute oral toxicity.

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Females
2000	2/3/3	10 min – 7 h	3 h – 6 h	67
300 (1^st )	0/0/3	--	--	0
300 (2^nd )	0/0/3	--	--	0
LD50 = >300 – 2000 mg/kg

* 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 oral Cat 4, H302
DSD: Xn, R22