2,6-dichlorobenzyl chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Oktober 1986 - November 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

12 May 1981

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,6-dichlorobenzyl chloride

EC Number:

217-940-4

EC Name:

2,6-dichlorobenzyl chloride

Cas Number:

2014-83-7

Molecular formula:

C7H5Cl3

IUPAC Name:

2,6-dichlorobenzyl chloride

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- males approx 7 weeks old, females 8 weeks
- fed with Altromin 1234 ad libitum except that they are fasted 16 hours befor and 3 - 4 after application

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Doses:

Dose finding: 1000 mg/kg BW, 3000 mg/kg BW, 5000 mg/kg BW
Main study: 1250 mg/kg BW, 2000 mg/kg BW, 3150 mg/kg BW

No. of animals per sex per dose:

Dose finding: 1
Main study: 5

Control animals:

no

Details on study design:

- Duration of observation period following administration
21 days, weekly weight check

- Necropsy of survivors performed: yes
All test animals were subjected to gross necropsy and result were recorded for each animal.

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Impairment of locomotor system and breathing, narrowed to closed palpebral fissure, lacrimation, drooling, palpebral fissure and snout encrusted with blood, diarrhea, hyperemia, hypersensitivity against touch, shivering, spasm, daze feeling as well as genereally lowered state of health.
At higher doses also speraded hind legs, swaying motion. These findings were not reversible withing 21 days, histopatologic investigations showed selective degeneration of granule cells in cerebellum.
Dead animals showed petechial bleeding in stormach wall, diacnostic findings in pankreas, kidneys, liver and melt. No macroscopic visible obervation in animals that were sacrified at end of the study.
Body weight development of surviving animals was decreased withing the first week, after 14 days all animals exceeded their starting weight.

Statistics:

probit analysis

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 100 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

2 120 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

2 080 mg/kg bw

Based on:

test mat.

Mortality:

1250 mg/kg BW: 1/5 (male) and 0/5 (female)
2000 mg/kg BW: 2/5 (male) and 3/5 (female)
3150 mg/kg BW: 4/5 (male) and 4/5 (female)

Clinical signs:

Impairment of locomotor system and breathing, narrowed to closed palpebral fissure, lacrimation, drooling, palpebral fissure and snout encrusted with blood, diarrhea, hyperemia, hypersensitivity against touch, shivering, spasm, daze feeling as well as genereally lowered state of health.
At higher doses also speraded hind legs, swaying motion. These findings were not reversible withing 21 days, histopatologic investigations showed selective degeneration of granule cells in cerebellum.

Body weight:

Body weight development of surviving animals was decreased withing the first week, after 14 days all animals exceeded their starting weight.

Gross pathology:

Dead animals showed petechial bleeding in stormach wall, diacnostic findings in pankreas, kidneys, liver and melt. No macroscopic visible obervation in animals that were sacrified at end of the study.

Applicant's summary and conclusion

Interpretation of results:

other: STOT SE 2

Conclusions:

LD50 of 2,6-dichlorobenzyl chloride is 2100 mg/kg body weight after single oral administration to Wistar rats for both sexes.
While the substance is not classified as acute toxic, observation of irreversible damage in brain at 2000 mg/kg body weight and 3150 mg/kg body weight in the surviving animals leads to classification as STOT SE 2.

Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item 2,6-dichlorobenzyl chloride when administered as a single oral dose to Wistar rats.

The procedure according to the OECD-Guidline 401 (Acute Oral Toxicity) was used. A prestudy using one male and female each was performed at 1000 mg/kg BW, 3000 mg/kg BW and 5000 mg/kg BW. At the lowest dose both animals survived, at the highest dose both died. At 3000 mg/kg BW the female died.

The doses in the main study were set as 1250 mg/kg BW, 2000 mg/kg BW and 3150 mg/kg BW. Deaths were as follows:

Dose [mg/kgBW]	Death male	Death female
1250	1/5	0/5
2000	2/5	3/5
3150	4/5	4/5

Animals were observed for 21 days after exposure, body weight was checked on weekly basis. After observation period all surviving animals were sacrified. Necropsy was performed.

The following clinical signs were observed:

Impairment of locomotor system and breathing, narrowed to closed palpebral fissure, lacrimation, drooling, palpebral fissure and snout encrusted with blood, diarrhea, hyperemia, hypersensitivity against touch, shivering, spasm, daze feeling as well as genereally lowered state of health.

At higher doses also speraded hind legs, swaying motion. These findings were not reversible withing 21 days, histopatologic investigations showed selective degeneration of granule cells in cerebellum.

Dead animals showed petechial bleeding in stormach wall, diacnostic findings in pankreas, kidneys, liver and melt. No macroscopic visible obervation in animals that were sacrified at end of the study.

Body weight development of surviving animals was decreased withing the first week, after 14 days all animals exceeded their starting weight.

LD50 was examined as 2100 mg/kg BW for both sexes, 2080 mg/kg BW for males, 2120 mg/kg BW for females. The substance is not classified as acute toxic but given the irreverible degeneration in animals brains, the substance is classified as STOT SE 2.