Chlorpyrifos

Endocrine disrupter mammalian screening – in vivo (level 3)

Administrative data

Endpoint:

endocrine disrupter mammalian screening – in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 440 (Uterotrophic Bioassay in Rodents: A Short-term Screening Test for Oestrogenic Properties)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: US EPA Guideline No. 890.1600

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Chlorpyrifos

EC Number:

220-864-4

EC Name:

Chlorpyrifos

Cas Number:

2921-88-2

Molecular formula:

C9H11Cl3NO3PS

IUPAC Name:

O,O-diethyl O-3,5,6-trichloropyridin-2-yl phosphorothioate

Test material form:

solid

Specific details on test material used for the study:

Chlorpyrifos Technical (milled)
Lot# KC28161419, TSN101285
Purity: 99.8%

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

State:

immature female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

3 days

Frequency of treatment:

once a day

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

0.5 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

1.5 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

4 mg/kg bw/day (nominal)

No. of animals per sex per dose:

6

Control animals:

yes, concurrent vehicle

Positive control:

17α-ethynyl estradiol (EE)

Examinations

Observations and examinations performed and frequency:

Daily observations and body weight measurements were recoreed.
On TD 4 (PND 22), animals were examined for precocious vaginal opening, weighed, euthanized, and the uteri were excised and weighed
before and after blotting.

Results and discussion

Endocrine disrupting potential:

negative

Maximum tolerated dose level exceeded:

yes

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

There were no significant differences in body weights at any dose level of chlorpyrifos. However, average body weight gains in 4 mg/kg bw/day chloropyrifos rats were decreased by 37.5% (TD 1- 2), 31.4% (TD 1-3), and 22.6% (TD 1- 4) compared with the vehicle control group. These results indicated that a maximum tolerated dose was achieved in this study. There were no significant treatment-related effects on body weight gains at dose ≤ 1.5 mg/kg bw/day chlorpyrifos. There were no significant differences in the body weights or body weight gains between the positive control group and the vehicle control group.

Organ weight findings including organ / body weight ratios:

no effects observed

Details on results:

Precocious vaginal opening was not observed in any rats on the day of termination (PND 22) as noted in the study file.

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

4 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: negative

Applicant's summary and conclusion

Conclusions:

Test substance was negative in the uterotrophic assay.

Executive summary:

To provide information on the potential for estrogenicity following short term exposure to chlorpyrifos, groups of 6 immature female Crl:CD(SD) rats were administered chlorpyrifos by oral gavage at dose levels of 0 (vehicle control), 0.5, 1.5, or 4 mg/kg bw/day beginning on postnatal day (PND) 19. A positive control group of 6 rats was exposed to 17α-ethynyl estradiol (EE) daily by gavage at 10 μg/kg bw/day. Rats in all treatment groups were dosed once daily for three days. On test day (TD) 4 (PND 22), animals were examined for precocious vaginal opening, weighed, euthanized, and the uteri were excised and weighed before and after blotting.

 

There was no animal mortality or treatment-related clinical signs observed in this study. There were no treatment-related changes in body weight in any chlorpyrifos-dosed animals and no significant differences in body weight gains at chlorpyrifos doses less than or equal to 1.5 mg/kg bw/day. At 4 mg/kg bw/day, body weight gain was significantly lower than the vehicle control group during TD 1- 3. Body weight gains for the 4-day study period at 4 mg/kg bw/day were decreased by 22.6% compared to the vehicle control group. There were no treatment-related effects on uterine weights in any chlorpyrifos-treated group compared to weights of the vehicle group with the terminal body weight as a covariate. The positive control group had the expected uterine weight increases without any significant change in body weight or body weight gain. No animal in this study had precocious vaginal opening. Uterine weights of the vehicle-treated animals met the performance criteria outlined in the applicable test guidelines, indicating acceptable assay sensitivity.

 

Overall, under the conditions of this study, there was no indication of estrogenicity from chlorpyrifos at doses ≤ 4 mg/kg bw/day, the highest dose level tested in female immature rats.