ethyl 2-(4-phenoxyphenyl)lactate

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

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:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.34 (One-Generation Reproduction Toxicity Test)

Deviations:

no

GLP compliance:

yes

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-220-9

EC Name:

-

Cas Number:

132584-17-9

Molecular formula:

C17 H18 O4

IUPAC Name:

ethyl 2-hydroxy-2-(4-phenoxyphenyl)propanoate

Test material form:

liquid

Specific details on test material used for the study:

Purity: 87.8%
Batch: MAY94MB002/005

Test animals

Species:

rat

Strain:

other: CR1:WI(Han)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

yes

Frequency of treatment:

Dosing regime (males): 7 days/week
Dosing regime (females): 7 days/week

Details on study schedule:

Number of litters per dose/conc.: 1 at mg/kg or mg/l

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

500 mg/kg bw/day (nominal)

Remarks:

Dose level started at 1000 mg/kg but was reduced to 500 mg/kg on day 3 of week 4

No. of animals per sex per dose:

Male: 20 animals at 1000 mg/kg or mg/l
Male: 20 animals at 500 mg/kg or mg/l
Female: 20 animals at 500 mg/kg or mg/l

Control animals:

yes

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

Administration of JG303 at 1000 mg/kg/day was found to be
poorly tolerated by male rats in terms of reduced food
intake and body weight loss. Therefore, males were not dosed
on Day 2 of Week 4 and dose level was reduced from day 3 of
Week 4 to 500 mg/Kg/day.

There was some apparent distress during treatment indicated
by salivation, paddling, mouth-rubbing and a slight raising
of the tail immediately after dosing in treated males from
Week 2 until the end of the study and in treated females
from Week 1 until the end of the study. These findings were
considered to be caused by taste aversion rather than
systemic toxicity.

From Week 4 of treatment the test males were observed as
having increased water consumption compared to controls and
they were provided with one extra water bottle per cage for
the rest of the study.

Overall, treated males lost weight between Weeks 2 and 3,
prior to reduction in the dose level from 1000 to 500
mg/kg/day. After this change to the dose level, mean body
weight gain in the males was similar to controls. There was
a treatment-related decrease in body weight gain in treated
females compared to controls from Day 14 of gestation until
Day 4 of lactation.

Mean food intake for treated males was lower than controls
over the first three weeks of dosing, but recovered after
the dose level was reduced. There was a reduction in food
intake in treated females over the entire lactation period,
compared to controls.

At necropsy seventeen treated males and six treated females
had macroscopically abnormal findings of the kidney that
included green, pale, irregular surface and large. These
findings were considered likely to have been caused by
treatment but their toxicological significance is unclear.
There were no microscopic findings in treated animas due to
effects of the test article.

In summary, JG303 was well tolerated by males and females at
500 mg/kg/day, but this was considered to be the maximum
tolerated dose level.

Effect levels (P0)

Dose descriptor:

NOEL

Effect level:

500 mg/kg bw/day (nominal)

Results: F1 generation

Details on results (F1)

Effects on F1 generation:
Mean number of implantations sites and consequently mean
number of pups born was significantly lower in treated
females (9.2 and 8.4, respectively) compared to controls
(11.8 and 11.1, respectively). There was no significant
difference between groups in birth weights or survival of
pups born. During lactation mean body weight gain in pups
from the treatment group was significantly lower than
controls. These were considered to be effects of treatment.

Overall reproductive toxicity

Key result

Reproductive effects observed:

no

Applicant's summary and conclusion

Conclusions:

JG303 was well tolerated by males and females at 500 mglkg/day, and in view of the post-treatment distress caused by apparent taste aversion, 500 mglkg/day can be considered to be the effective no observed toxic effect level. The slight reduction in implantation and reduction in body-weight gain of offspring in the treated group at the apparent highest tolerated dose level is not considered to warrant classification of substances as hazardous in relation to reproductive effects.