Ethyl 6,8-dichlorooctanoate

Endpoint summary

Description of key information

Effects of the test substance were noted in the high and the mid dosed amimals of both sexes at observations in life, and clinical chemistry, organ weight determination and at histopathological examination.

Two major effects of the test substance were thereby elucidated:

Firstly, the test substance caused salivation for a short time after administration. This could be due to a vagotonic effect or to an extremely poor palatability, as minimal amounts to the test may be deposited in the oral cavity even at a careful gavage.

Secondly, the test substance is hepatotoxic. Findings at clinical chemistray, organ weight determiantion and histopathology together indicate the presence of a mild hepatocellular degeneration.

Some other significant differences or abnormal findigs are considered to be incidental significances (e. g. in the feed consumption, heart weight changes etc.) or secondary changes (adrenal weight increase due to chronic stress).

The changes noted did not become life threatening.

The hepatic changes partly persisted until the end of the recovery period, but were clearly reduced in severity.

There was no marked sex differende in the dose response.

Toxic effects were present in the mid and the high dosed group of both exes, none were observed in the low dosed group.

Based on the results of the study, the NOAEL is 60 mg 6,8 Dichloroethylcaprylate per kg body weight and day in rats of both sexes

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-01-14 to 2000-05-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Specific details on test material used for the study:

Batch: Ds 1099

Species:

rat

Strain:

Fischer 344

Remarks:

"CDF (F344)/CRLBR, SPF." as cited in Report

Sex:

male/female

Details on test animals or test system and environmental conditions:

Room temperature Average 20.7°; humidity average 49.2%

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5% Solution in Water

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 days

Frequency of treatment:

once a day

Dose / conc.:

0 mg/kg bw/day (nominal)

Dose / conc.:

60 mg/kg bw/day (nominal)

Dose / conc.:

190 mg/kg bw/day (nominal)

Dose / conc.:

600 mg/kg bw/day (nominal)

Dose / conc.:

600 mg/kg bw/day (nominal)

Remarks:

recovery group

No. of animals per sex per dose:

5 male and 5 female

Control animals:

yes, concurrent vehicle

Positive control:

no

Observations and examinations performed and frequency:

Body weight; chromodqakryorrhoea, diarrhoea, salivation, behaviour, feed consumption

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

effects observed, non-treatment-related

Description (incidence and severity):

Feed consumption of high dose recovery males and female was significantly hgher in teh last week of the dosing period (Day 21 through 28) compared to the controls this significance is not given toxicological importance.

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

eosinophil granulocytes females higher in Low dose
cholesterol males lower in mid dose and high dose
cholesterol females lower in mid dose and high dose
alkaline phosphatase females higher in mid dose
ALT females higher in mid dose and high dose
AST females higher in mid dose and high dose
BUN females higher in mid dose and high dose
Na+ females lower in high dose

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

liver weight males higher in mid dose and hgh dose
liver weight females higher in mid dose and hgh dose
adrenals weight males higher in high dose after recovery
heart weight males lower in mid dose

Key result

Dose descriptor:

NOAEL

Effect level:

60 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

organ weights and organ / body weight ratios

Critical effects observed:

not specified

Conclusions:

Based on the results of the study, the NOAEL is 60 mg 6,8 Dichloroethylcaprylate per kg body weight and day in rats of both sexes

Executive summary:

Effects of the test substance were noted in the high and the mid dosed amimals of both sexes at observations in life, and clinical chemistry, organ weight determination and at histopathological examination.

Two major effects of the test substance were thereby elucidated:

Firstly, the test substance caused salivation for a short time after administration. This could be due to a vagotonic effect or to an extremely poor palatability, as minimal amounts to the test may be deposited in the oral cavity even at a careful gavage.

Secondly, the test substance is hepatotoxic. Findings at clinical chemistray, organ weight determiantion and histopathology together indicate the presence of a mild hepatocellular degeneration.

Some other significant differences or abnormal findigs are considered to be incidental significances (e. g. in the feed consumption, heart weight changes etc.) or secondary changes (adrenal weight increase due to chronic stress).

The changes noted did not become life threatening.

The hepatic changes partly persisted until the end of the recovery period, but were clearly reduced in severity.

There was no marked sex differende in the dose response.

Toxic effects were present in the mid and the high dosed group of both exes, none were observed in the low dosed group.

Based on the results of the study, the NOAEL is 60 mg 6,8 Dichloroethylcaprylate per kg body weight and day in rats of both sexes

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

60 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

one short term repeated dose toxicity study has been performed according to guideline.

Organ:

liver

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the study result a classification as STOT RE cat 2 / H373 is necessary