2'-aminoacetophenone

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Maternal Ingestion of Ortho-Aminoacetophenone During Gestation Affects Intake by Offspring

Author:

Nolte, D.L. and Mason, J.R.

Year:

1995

Bibliographic source:

Physiology & Behavior, Vol. 58, No. 5, pp. 925-928

Materials and methods

Principles of method if other than guideline:

- Principle of test: The effect of maternal ingestion of the test substance via drinking water during gestation on substance intake by offspring via drinking water
- Short description of test conditions: Pairs of male and female mice were given the test substance at 0.1% in drinking water or tap water (negative control) from mating until gestation day 18. All litters were reduced to 6 male pups on postparturition day 11, and 15 litters each from the test and control groups were selected for subsequent behavioural testing. Litters were weaned on postparturition day 21.
From each litter consisting of 6 males, 3 pups were selected for behavioural testing at weaning from postnatal day 25 (first cohort), the remaining 3 pups were subject to behavioural testing as subadults from postnatal day 87 (second cohort). Parental males were likewise tested after having been separated from the females on gestation day 18 (third cohort).
- Parameters analysed / observed: For behavioural testing, following an adaptation and pre-treatment period without test substance exposure, each cohort was divided into 3 subcohorts which were presented the test substance at 0.1, 0.25 and 0.5% in drinking water for 3 h, respectively. Water intake was measured and compared to the 3-hour water intake measured during the pre-treatment period in order to determine the relative avoidance both per test substance concentration and treatment during gestation.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2'-aminoacetophenone

EC Number:

209-002-8

EC Name:

2'-aminoacetophenone

Cas Number:

551-93-9

Molecular formula:

C8H9NO

IUPAC Name:

1-(2-aminophenyl)ethan-1-one

Test material form:

solid: crystalline

Test animals

Species:

mouse

Strain:

CF-1

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 90-95 days
- Housing: animals were caged as pairs during mating and gestation up to gestation day 18, and individually thereafter.
- Diet: Wayne Rodent Blox, ad libitum
- Water: tap water, ad libitum (except during adaptation and pre-treatment period)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: the test substance was mixed with tap water to prepare a 0.1% (w/w) stock emulsion.

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

- Impregnation procedure: cohoused
- M/F ratio per cage: 1/1
- Length of cohabitation: from mating to gestation day 18
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy

Duration of treatment / exposure:

from mating to gestation day 18

Frequency of treatment:

continuous

Duration of test:

Parental animals were treated with the test substance until gestation day 18.
Offspring males were subject to behavioural testing from post-natal day 25 (first cohort), and post-natal day 87 (second cohort).
Parental males were subject to behavioural testing after gestation day 18 (third cohort).

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.1 other: %

Remarks:

during mating and gestation (parental animals)

Doses / concentrations 2

Dose / conc.:

0.1 other: %

Remarks:

for behavioural testing (offspring and parental males)

Doses / concentrations 3

Dose / conc.:

0.25 other: %

Remarks:

for behavioural testing (offspring and parental males)

Doses / concentrations 4

Dose / conc.:

0.5 other: %

Remarks:

for behavioural testing (offspring and parental males)

No. of animals per sex per dose:

Parental animals (control): 22 pairs
Parental animals (test group): 22 pairs
Offspring: 6 males per litter (out of 15 litters)

Control animals:

yes, concurrent no treatment

Details on study design:

- Dose selection rationale: The test substance is known to be aversive to mice. The substance has been reported to reduce fluid intake by mice and to virtually eliminate ingestion at concentrations 1% and above.

Results and discussion

Any other information on results incl. tables

All subcohorts within an age cohort ingested similar amounts of water during the pretreatment period. At 26 days of age, pups born to mothers that ingested the test substance during gestation ingested more test substance-treated water than did offspring from mothers given water (F = 11.2070, df 1.84, P = 0.0016). Further, regardless of exposure, there was an inverse relationship between intake and test substance concentration (F = 259.249, df 2.84, P < 0.0001). There was not an interaction between exposure and test concentration (F = 0.703, df 2.84, P > 0.35).

Offspring tested at 88 days of age responded similarly to those tested at 26 days of age. Prior experience with the test substance enhanced their intake during the treatment period (F = 8.555, df 1.83, P = 0.0047), mice restricted their intake with increasing test concentrations (F = 113.701, df 2.83, P < 0.0001) and no interaction between exposure and concentration occurred (F = 0.352, df 2.83, P > 0.35).

Adult experiences with the test substance, however, did not enhance their intake during subsequent trials (F = 0.733, df 1.35, P > 0.35). As with the other cohorts, there was a test substance concentration effect (F = 30.310, df 2.35, P < 0.0001) but no exposure by concentration interaction (F = 0.884, df 2.35, P > 0.35).

Applicant's summary and conclusion

Conclusions:

Mice restricted their intake of all concentrations of the test substance regardless of treatment during gestation. This result is consistent with the notion that the test substance is avoided by mice at concentrations ranging from 0.25-1.0%. Nevertheless, the data also demonstrate that prenatal experience with the test substance was associated with increased ingestion of the test substance.