O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2 March 1983 to 6 May 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

not applicable

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate

EC Number:

255-255-2

EC Name:

O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate

Cas Number:

41198-08-7

Molecular formula:

C11H15BrClO3PS

IUPAC Name:

4-bromo-2-chlorophenyl ethyl (propylsulfanyl)phosphonate

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Analytical verification of doses or concentrations:

no

Details on mating procedure:

Rabbits were paired 1:1, with does placed in the buck's cage. When mating was observed the dose was weighed and lutenizing hormone was injected into the marginal ear vein. The doe was then returned to her cage.

Duration of treatment / exposure:

GD 6 -18/ oral gavage

Frequency of treatment:

daily

Duration of test:

12 days

No. of animals per sex per dose:

16 females

Control animals:

yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

ca. 90 mg/kg bw/day (nominal)

Based on:

not specified

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

ca. 175 mg/kg bw/day (nominal)

Based on:

not specified

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

175 mg/kg bw/day

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: the test material was devoid of embroyonic or teratogenic activity in New Zealand White rabbits up to a maximum dose of 175 mg/kg/day

Overall developmental toxicity

Developmental effects observed:

no

Lowest effective dose / conc.:

175 mg/kg bw/day

Treatment related:

not specified

Applicant's summary and conclusion

Conclusions:

In conclusion, CGA 15324 technical was devoid of embroyonic or teratogenic activity in New Zealand White rabbits up to a maximum dose of 175 mg/kg/day. The maternal NOAEL was deemed to be 90 mg/kg/day due to reduced food consumption at 175 mg/kg/day.

Executive summary:

The embryotoxic and teratogenic potential of CGA-15324 Technical was evaluated in albino rabbits. The test material was administered by gavage to inseminated female rabbits at dose levels of 0, 30, 60, 90 or 175 mg/kg/day from day 6 through to 18 of gestation. Each dose level consisted of 16 does. On GD 30 does were euthanised and laparohysterectomies were performed.

 

Maternal mortality was observed in the control (1); 60 (2) and 175 (9 does) mg/day groups. Changes in clinical signs were observed in all groups. These changes were observed consistently in the high dose group and consisted of anorexia (reduced food intake), diarrhoea,soft stool and oral and perianal discharges.

 

The lesions observedin the animals that died on the study were necropsied, primarily involved yellow discolouration of the mesentery in the gastric region and pinpoint haemorrhages in the stomach. No gross lesions were observed in any of the animals suriviving to laparohysterectomy.

 

No statisitically significant differences were observed between the control and treated groups for bodyweight gain during gestation, maternal mortality, or mean copora lutea. Because the 175 mg/kg/day group constituted the maternal multi-dose LD50, the mortality observed in the high dose group was considered biologically relevant.

 

No significant differences were observed for the following measures of prenatal toxicity: mean number of implantations; litter size; foetal body weight; or embryolethality. No significant differences were detected between the control and treated groups for malformations or variations.

 

In conclusion, CGA 15324 technical was devoid of embroyonic or teratogenic activity in New Zealand White rabbits up to a maximum dose of 175 mg/kg/day. The maternal NOAEL was deemed to be 90 mg/kg/day due to reduced food consumption at 175 mg/kg/day.