Fatty acids, sunflower-oil, conjugated, maleated,reation products with diethanolamine, maleated tall-oil fatty acids and triethanolamine

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:

other: Range-finding study, acceptable, well-documented study report which meets basic scientific principles

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Range-finding study

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-iminodiethanol

EC Number:

203-868-0

EC Name:

2,2'-iminodiethanol

Cas Number:

111-42-2

Molecular formula:

C4H11NO2

IUPAC Name:

2,2'-iminodiethanol

Details on test material:

- Name of test material (as cited in study report): Diethanolamine
- Batch: sample 929 from container B 810
- Physical state/appearance: Liquid / colorless
- Purity: >98.7%
- Homogeneity: homogeneous
- Stability: The stability under storage conditions was confirmed by reanalysis
- Storage conditions: Room temperature, without light and oxygen under N2

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K Thomae GmbH, Biberach Germany
- Age at study initiation: 68-70 days
- Weight at study initiation: ca. 214 g
- Housing: individual in wire mesh cages
- Diet: Kliba rat/mouse laboratory diet, Klingenthalmühle AG Kaiseraugst, Switzerland ad libitum
- Water: Tap water ad libitum
- Acclimation period: 5 days
- Adaption period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

nose/head only

Vehicle:

unchanged (no vehicle)

Details on exposure:

The test substance was supplied to a two-component atomizer at a constant rate by means of a metric pump. An aerosol was generated by means of compressed air and passed into the inhalation system.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Concentrations: Target: 0; 0.1; 0.2; 0.4 mg/l (analytical determined: 0; 0.11; 0.21; 0.40 mg/l)

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/1-4
- Length of cohabitation: 4 pm - 7.30 am
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy:sperm in vaginal smear referred to as day 0 of pregnancy

Duration of treatment / exposure:

gestation days 6 - 15

Frequency of treatment:

6h/day

Doses / concentrations

Remarks:

Doses / Concentrations:
0; 0.1; 0.2; 0.4 mg/l (analytical determined: 0; 0.11; 0.21; 0.40 mg/l, head nose exposure)
Basis:
nominal conc.

No. of animals per sex per dose:

10 females

Control animals:

yes, concurrent vehicle

Details on study design:

Duration of test: 20 days

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Test group 0.4 mg/l: absolute and relative liver weight increased increase in sodium and creatinine serum concentrations decrease in cholesterol and triglycerides serum concentrations;
Test group 0.2 mg/l: relative liver weight increased increase in sodium and creatinine serum concentrations decrease in cholesterol and triglycerides serum concentrations;
Test group 0.1 mg/l: No treatment related effects.

Effect levels (maternal animals)

Dose descriptor:

NOAEC

Effect level:

0.2 mg/L air

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Test group 0.4 mg/l: significantly increased mean placental weights
Test group 0.2 mg/l: significantly increased mean placental weights

Effect levels (fetuses)

Remarks on result:

not determinable because of methodological limitations

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

no

Any other information on results incl. tables

Results summay:

The exposure of pregnant female Wistar to an aerosol of Diethanolamine in a head/nose exposure systems for 6 h/day on day 6 through day 15 post coitum at concentrations of 0; 0.1; 0.2; 0.4 mg/l led at 0.4 mg/l to a marked indication of hepatotoxic effects (increase of absolute and relative liver weights, decrease in cholesterol and triglyceride serum concentration, increase in transaminase AST). At 0.2 mg/l relative liver weight was still increased and cholesterol and triglycerides decreased.

These findings were considered as clear indications for maternal toxicity.

Detailed results:

- Concentrations:
Target        Measured        MMAD (GSD)
0.1 mg/l,       0.11 mg/l        0.6 µm (4.5)
0.2 mg/l        0.21 mg/l        0.1.2 µm (3.6)
0.4 mg/l        0.40 mg/l        0.0.6 µm (4.5)

- Mortalities, clinical findings, body weight:
No deaths nor treatment related finding

Weight of placentae

No substance related effects were observed. The marginal,however statistically significant  decrease in the mean placental weights in test groups 2 and 3 is without any biological relevance.