Triethyl phosphite

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Adopted according to OECD SIDS (publicly available peer reviewed source). Original document not available.

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

SIDS Initial Assessment Report For SIAM 16 (Triethyl Phosphite), 2003 Paris.

Author:

OECD

Year:

2003

Bibliographic source:

UNEP Publications

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Triethyl phosphite

EC Number:

204-552-5

EC Name:

Triethyl phosphite

Cas Number:

122-52-1

Molecular formula:

C6H15O3P

IUPAC Name:

triethyl phosphite

Details on test material:

Purity: 99.3%

Test animals

Species:

rat

Strain:

other: SPF bred Wistar rats (Hsd Cpb:WU)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Weight:
Males: between 318 and 353 g
Females: 192-214 g
Age: 11 weeks (m), 12 weeks (f)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Polyethylenglycol 400

Details on mating procedure:

- M/F ratio per cage: 1:1
- Length of cohabitation: overnight

Duration of treatment / exposure:

Two weeks before mating, during the 2 week mating and 1-week remating period, during gestation, lactation and up to the day before necropsy
(males were necropsied on day 36 to 37 of treatment, females between day 4 to 6 post partum).

Frequency of treatment:

Once daily.

Details on study schedule:

Duration of test: 12 weeks

Doses / concentrations

Remarks:

Doses / Concentrations:
10, 80, 320, 640 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

treatment group: 12 males and 12 females.
control group: 15 males and 15 females.

Control animals:

yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:

PARAMETERS: Mortality, observation, body weight, food consumption, water consumption, time to insemination, insemination index, fertility index, duration of gestation, gestation index, number of corpora lutea, number of implantations.

Litter observations:

F1 pups: appearance (including externally visible malformations), general behaviour, mortality, sex ratio at birth, individual weights at birth and on day 4 after birth.

Postmortem examinations (parental animals):

Necropsy, histopathology (testes, epididymides, ovaries, mammae, uterus, vagina and organs with macroscopically altered tissues).

Statistics:

ANOVA, chi-square. Fisher`s exact test, F-test and additional t-test or Welch-t-test, significance levels p=0.05 and 0.01.

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

MORTALITY
F0
640 mg/kg: male, 1/12 (d 20, not treatment related)
640 mg/kg: female, 12/12 (d 23-25 =mating or early gestation, moribund)


OBSERVATION:
F0:
salivation (all groups including control, immediately after dosing, dose dependently increased incidence)
640 mg/kg:
male: tremors (1/11), piloerection (6/11), sunken sides (6/11), skin lesion (1/11)
female (all): hypoactivity, piloerection, sunken sides, circling behavior, skin lesion, loss of weight, recumbency,
320 mg/kg:
female (1/12): hypoactivity, piloerection, sunken sides, high stepping gait


BODY WEIGHT GAIN:
F0:
males and females: 640 mg/kg: transient increase, then severe decrease; overall: no weight gain at all = >14% decrease relative to control in males and females slight effects in individuals at 80 (before the increase of weight due to gestation) and 320 mg/kg bw


FOOD CONSUMPTION:
males: no effect
females: possibly slight reduction during lactation at 80 mg/kg bw (highest dose at that time; no surviving pups at 320 mg/kg bw)

WATER CONSUMPTION:
males + females: no effect

NECROPSY: 640 mg/kg: female: small spleen in moribund rats

ORGAN WEIGHTS:
testes: 640 mg/kg: abs: slight decrease (Control: 1.637g, treated: 1.321g); rel: slight increase (Control:0.868%, treated: 0.981%)
Relative testes weights (%) were 0.87, 0.89, 0.91, 0.85, 0.98** for controls, 10, 80, 320 and 640 mg/kg bw/day groups, respectively; there was no significnat difference in absolute testes weights between the groups.

HISTOPATHOLOGY:
(reproductive organs + macroscopically altered tissues)
males: 640 mg/kg: testes: min.-slight cell degeneration
females: 640 mg/kg: mammary gland: slight proliferation/ secretion, vagina+cervix: mucification
spleen: reduced lymphoid cellularity (perimortal)
males+females: <=320 mg/kg: no treatment related effects

TIME TO INSEMINATION:
increase at 320 mg/kg

INSEMINATION INDEX:
0 - 320 mg/kg: 100%
640 mg/kg: 41,7 %

FERTILITY INDEX:
0 mg/kg : 60 %
10 mg/kg : 75%
80 mg/kg : 100%
320 mg/kg: 58,3 %
640 mg/kg: no surviving dam

DURATION OF GESTATION:
reduction at 320 mg/kg

GESTATION INDEX:
0 mg/kg : 100 %
10 mg/kg : 100 %
80 mg/kg : 100 %
320 mg/kg: 28,6 %
640 mg/kg: no surviving dam

NUMBER OF CORPORA LUTEA, NUMBER OF IMPLANTATIONS: no effects
LITTER SIZE: no effect

Effect levels (P0)

1

Dose descriptor:

NOAEL

Remarks:

Fertility

Effect level:

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

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Reduction of gestation index.

2

Dose descriptor:

NOAEL

Remarks:

Fertility

Effect level:

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

Based on:

test mat.

Sex:

male

Basis for effect level:

other: Mortality at 640 mg/kg bw.

Results: F1 generation

Details on results (F1)

SEX RATIO OF PUPS: 320 mg/kg: reduction of males (equivocal due to small number of pups)
FETAL DEVELOPMENT: In F1 developmental parameters were not affected by treatment up to and including doses of 80 mg/kg bw/day, while evaluation was not possible at higher doses as there were no surviving pups. No externally malformed pups were observed.

MORTALITY
F1:
320 mg/kg: 13/13 (1 day after birth)

OBSERVATION:
F1:
>= 320 mg/kg bw/day: hypothermia, low birth weight

BODY WEIGHT GAIN:
F1:
<= 80 mg/kg: no effect

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Mortality in the 320 mg/kg bw dose group.

Overall reproductive toxicity

Reproductive effects observed:

not specified