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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific prnciples.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
2007
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
Groups of 25 time-mated female Sprague–Dawley rats were given 0, 100, 300, or 1000 mg DIPA/kg/day on gestation days 6 through 20 by oral gavage.
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Diisopropanolamine
- Analytical purity: ranged from 98.8 % - 99.6 %

Test animals

Species:
rat
Strain:
other: CRL:CD(SD)
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Inc. (Kingston, New York and Raleigh, North Carolina)
- Diet: LabDiet #5002 Certified Rodent Diet (PMI Nutrition International, St. Louis, MO) ad libitum
- Water: tap water ad libitum



ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25 °C
- Humidity (%): 45-60 %
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
yes
Details on mating procedure:
- Impregnation procedure: purchased timed pregnant
Duration of treatment / exposure:
Gestation days 6-20
Frequency of treatment:
daily
Duration of test:
21 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 300 or 1000 mg/kg bw/day
Basis:
nominal conc.
No. of animals per sex per dose:
25 (females only)
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21
- Organs examined: The weights of the kidneys, liver and gravid uteri were obtained and the kidneys, liver and all gross lesions were preserved in 10% NBF.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes

Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: Yes: half per litter
Statistics:
Means and standard deviations were calculated for all continuous data. These parameters were first examined for equality of variance using Bartlett’s test (a = 0.01; Winer, 1971). If the results of the Bartlett’s test were significant, the data were transformed in an attempt to obtain equality of variances. The order of transformations used was the common log, the inverse and the square root with the best fit used for subsequent statistical testing. Maternal body weight, weight gain, feed consumption, organ weights and fetal body weights were analyzed using parametric or non-parametric ANOVA followed by Dunnett's or Wilcoxon's test for comparison to controls; pre- and post-implantation loss were evaluated using a Censored Wilcoxon's test; Corpora lutea, implantations and litter size were analyzed using non-parametric ANOVA follewed by Wilcoxon's test; pregnancy rates were evaluated using Fisher exact probability test; and fetal sex ratios were analyzed using a binomial distribution test. As statistical interactions (i.e., time by dose or sex by dose) were identified in several of the tests, the alpha levels for interaction terms were set a priori at 0.01–0.10, with Bonferroni’s correction. The alpha level for comparison of individual dose groups to controls was set a priori at 0.05.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: fetotoxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion