diethyleneglycyl bis (chloroacetate)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-08-23 to 2000-09-13

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1996

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

1996

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

1998

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-{2-[(2-chloroacetyl)oxy]ethoxy}ethyl 2-chloroacetate

Cas Number:

106-78-5

Molecular formula:

C8H12O5Cl2

IUPAC Name:

2-{2-[(2-chloroacetyl)oxy]ethoxy}ethyl 2-chloroacetate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

HsdCpb:WU / SPF-bred

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, District of Paderborn
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Age at study initiation: approx. 8 - 9 weeks
- Weight at study initiation: 190-234 g males, 160-71 g females
- Fasting period before study: approx. 17 hours ±2 hours
- Housing: polycarbonate cages; bedding low-dust wood granules type BK 8/15
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2.0°C
- Humidity (%): approx. 55 ± 5%
- Air changes (per hr): approx. 15-20 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours, illumination from 5 a.m. to 5 p.m.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: demineralized water with the aid of Cremophor EL 2% (v/v)

Details on oral exposure:

VEHICLE
- demineralized water with the aid of Cremophor EL 2% (v/v)

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body

Doses:

25, 200 and 2,000 mg/kg bw

No. of animals per sex per dose:

6 males and 9 females

Details on study design:

- Appearance and behavior were recorded several times on the day of treatment, and at least once a day thereafter. Where signs occurred, the type, period and intensity (1 = weak, 2 = moderate up to strong) were determined individually.
- During clinical observation all abnormal findings were registered and particular attention is paid to the following organ systems, localizations and physiological functions:
Appearance: fur, skin color, edemas, eyes, lacrimation, nasal discharge, salivation etc.
Behavior: grooming, vocalization, excitement, aggression, digging and preening movements, cannibalism etc.
Nervous system: reactivity, motility, reflexes, gait, paralysis, spasms, tremors etc.
Respiration: where assessable, e.g. frequency etc.
Cardiovascular system: where assessable, e.g. heart rate, pallor etc.
Posture: ventral, lateral recumbency etc.
Gastrointestinal functions: appearance of feces etc.
- Post-treatment Observation: The post-treatment observation period lasted for at least 14 days
- Body Weights: The body weights of the rats are recorded on day 1 before administration and then weekly. Additionally, all animals that died or are sacrificed are weighed.
- Necropsy: After the end of the post-treatment observation period the animals are anesthetized by inhaling diethyl ether and sacrificed. They are then subjected to a gross pathology examination, as are any animals which may have died intercurrently.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 30 - < 50 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 50 - < 200 mg/kg bw

Based on:

test mat.

Mortality:

A dose of 25 mg/kg was tolerated by males and females without mortalities.
200 and 2,000 mg/kg were lethal for all females and 200 mg/kg for two males. The animals died on day 1 of the study.

Clinical signs:

other: A dose of 25 mg/kg was tolerated by males and females without clinical signs. At 200 mg/kg and above in both sexes the motility and the reactivity were decreased, gait uncoordinated, breathing labored, and the animals lay in abdominal position. Additional

Gross pathology:

In animals that died during the observation period dark-red discolored livers and slightly collapsed lungs were detected.
No gross pathologic changes were observed in animals sacrificed at the end of the study period

Any other information on results incl. tables

Table 1

Dose (mg/kg b.w.)	Toxicological results*			Duration of signs	Time of death	Mortality [%]
male
25	0	0	3	–	–	0
200	2	3	3	2h – 2d	5h	67
female
25	0	0	3	–	–	0
200	3	3	3	2h – 5h	3h – 5h	100
2000	3	3	3	10´ – 2h	40´ – 2h	100

* 1st column= number of dead animals; 2nd column = number of animals with signs; 3rd column= number of animals in the group

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

L050 rat: >30 <50 mg/kg bw