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Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data from secondary source

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
Reregistration Eligibility Decision (RED) for test material
Author:
US EPA
Year:
1998
Bibliographic source:
Prevention, Pesticides Toxic Substances ,US EPA archive document ,September 1998 )
Reference Type:
secondary source
Title:
Reproductive and developmental toxicity study of test material
Author:
HSDB
Year:
2018
Bibliographic source:
.S. National Library of Medicine, National Institutes of Health, Health & Human Services, 2018

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Developmental toxicity study of test material was performed on female CD rats.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
N,N-diethyl-m-toluamide
EC Number:
205-149-7
EC Name:
N,N-diethyl-m-toluamide
Cas Number:
134-62-3
Molecular formula:
C12H17NO
IUPAC Name:
Diethyltoluamide
Details on test material:
- Name of test material (as cited in study report):DEET (N,N-Diethyl-Meta-Toluamide),- Molecular formula :C12H17NO- Molecular weight : 191.272g/mol- Substance type: Organic

Test animals

Species:
rat
Strain:
other: CD
Details on test animals or test system and environmental conditions:
No data available

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on exposure:
No data available
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
mated female used
Duration of treatment / exposure:
14 days (from days 6 to 15 of gestation)
Frequency of treatment:
daily
Duration of test:
No data available
Doses / concentrations
Remarks:
0, 125, 250or 750 mg/kg/day
No. of animals per sex per dose:
Total:1000 mg/kg bw/day:25 females 125 mg/kg bw/day:25 females 250mg/kg bw/day:25 females 750mg/kg bw/day: 25 females
Control animals:
yes, concurrent vehicle
Details on study design:
No data available

Examinations

Maternal examinations:
Parental animals observation and examinationsCAGE SIDE OBSERVATIONS: yes DETAILED CLINICAL OBSERVATIONS: Yes Time schedule: BODY WEIGHT: YesTime schedule for examinations: FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: no Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data availableWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data Time schedule for examinations: OTHER:
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes Examinations included: - Gravid uterus weight: Yes - Number of corpora lutea: No data - Number of implantations: No data - Number of early resorptions: No data - Number of late resorptions: No data - Other:
Fetal examinations:
- External examinations: Yes: all per litter - Soft tissue examinations: Yes: all per litter - Skeletal examinations: Yes: all per litter - Head examinations: No data
Statistics:
No data available
Indices:
No data available
Historical control data:
No data available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Clinical signs such as hypoactivity, ataxia, decreased muscle tone, foot splay, perinasal encrustation, and perioral wetness were observed; some of these signs were suggestive of neurotoxicity in this dose group because none of these signs were seen in the controls. Some of these clinical signs were seen only sporadically in the other treated groups.
Dermal irritation (if dermal study):
not specified
Mortality:
mortality observed, treatment-related
Description (incidence):
In the 750mg/kg /day dose group dams, there was an increase in mortality rate,
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
In the 750mg/kg /day dose group dams, there was an a reduction in body weight gain
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
In the 750mg/kg /day dose group dams, there was an a reduction in food consumption,
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
an increase in mean liver weights.
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
effects observed, treatment-related
Description (incidence and severity):
A slight increase in percent post-implantation loss was seen in the 750mg/kg/day dose group
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
not specified

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
> 250 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
body weight and weight gain
clinical signs
food consumption and compound intake
mortality
organ weights and organ / body weight ratios
pre and post implantation loss
Remarks on result:
other: overall no toxic effects observed

Maternal abnormalities

Abnormalities:
not specified
Localisation:
not specified

Results (fetuses)

Fetal body weight changes:
effects observed, treatment-related
Description (incidence and severity):
a statistically-significant decrease in mean fetal body weight/litter was seen in the 750mg/kg /day dose group
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Reduction in number of live offspring:
not specified
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Description (incidence and severity):
The incidence of external variations and/or malformations were comparable in the control and treatment groups
Skeletal malformations:
no effects observed
Description (incidence and severity):
The incidence of skeletal variations and/or malformations were comparable in the control and treatment groups
Visceral malformations:
no effects observed
Description (incidence and severity):
The incidence of visceral variations and/or malformations were comparable in the control and treatment groups
Other effects:
not specified

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
reduction in number of live offspring
external malformations
skeletal malformations
visceral malformations
Remarks on result:
other: overall no developmental toxic effects observed

Fetal abnormalities

Abnormalities:
not specified
Localisation:
other: not specified

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified
Relation to maternal toxicity:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
No Observed Effect Level (NOEL) for developmental toxicity was considered to be 250mg/kg/day, When female CD rats were treated with test material orally.
Executive summary:

Developmental toxicity study of test material was performed on mated female CD rats. Undiluted test material in dose concentration0, 125, 250, or 750 mg/kg/day were administered via oral gavage route from days 6 to 15 of gestation.Control animals received corn oil .Twenty-five mated female rats per group were used in study. Clinical signs, body weights, food consumption, maternal liver and gravid uterine weights, maternal ovarian and uterine examination were noted. fetal external examinations and internal soft-tissue and skeletal examinations were carried out.In the 750mg/kg/day dose dams clinical signs such as hypoactivity, ataxia, decreased muscle tone, foot splay, perinasal encrustation, and perioral wetness were observed; some of these signs were suggestive of neurotoxicity in this dose group because none of these signs were seen in the controls. Some of these clinical signs were seen only sporadically in the other treated groups. In the high-dose dams, there was an increase in mortality rate, a reduction in body weight gain and food consumption, and an increase in mean liver weights. A slight increase in percent post-implantation loss was seen in the 750mg/kg/day dose group and a statistically-significant decrease in mean fetal body weight/litter was seen in the 750mg/kg/day dose group. No additional compound-related effects were found.The incidence of external, visceral, and skeletalvariations and/or malformations were comparable in the control and treatment groups. HenceNo Observed Effect Level (NOEL) for developmental toxicity was considered to be 250mg/kg/day,When femaleCD rats were treated withtest material orally.