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EC number: 218-792-3 | CAS number: 2235-46-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicity to reproduction
Administrative data
- Endpoint:
- two-generation reproductive 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:
- 1 998
- 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:
- 2 018
- Bibliographic source:
- U.S. National Library of Medicine, National Institutes of Health, Health & Human Services, 2018
- Reference Type:
- secondary source
- Title:
- Toxicological Profile for test material
- Author:
- Agency for Toxic Substances and Disease Registry
- Year:
- 2 017
- Bibliographic source:
- Toxicological Profile for test material ,ATSDR, August 2017
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- Reproductive and Developmental toxicity study of test material was performed on Sprague Dawley rats.
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- No data available
Test material
- 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 :191.2723g/mol - Substance type: Organic
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- No data available
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data available
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- not specified
- Details on exposure:
- No data available
- Details on mating procedure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- F0: 80 days before mating during mating, gestation, and lactation.F1: 93 days before mating during mating, gestation, and lactation.
- Frequency of treatment:
- daily
- Details on study schedule:
- No data available
Doses / concentrations
- Remarks:
- 0, 500, 2,000, or 5,000 ppm ( 0, 25, 100, or 250 mg /kg/day)
- No. of animals per sex per dose:
- Total:1120 mg/kg bw/day:28 male and 28 female 25 mg/kg bw/day:28 male and 28 female100 mg/kg bw/day:28 male and 28 female250mg/kg bw/day:28 male and 28 female
- Control animals:
- yes
- Details on study design:
- No data available
- Positive control:
- No data available
Examinations
- Parental animals: Observations and examinations:
- Parental animals observation and examinationsCAGE SIDE OBSERVATIONS: yes DETAILED CLINICAL OBSERVATIONS: Yes Time schedule: twice daily BODY WEIGHT: YesTime schedule for examinations: twice dailyFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): twice dailyFood 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:
- Oestrous cyclicity (parental animals):
- No data available
- Sperm parameters (parental animals):
- No data available
- Litter observations:
- The F1 and F2 litters were observed for number of live and stillborn pups, external anomalies, sex and body weight grouped by sex on lactation days 0, 4, 7, and 14, sex and individual body weights (only group weights reported) on lactation day 21, viability, and behavioral abnormalities at least twice daily during lactation.
- Postmortem examinations (parental animals):
- Postmortem examinations (Parent Animal)SACRIFICE :yes GROSS NECROPSY: yes gross necropsy and histological examination of the ovaries, prostate, seminal vesicles, testes with epididymides, uterus, vagina, and all gross lesions were conducted in all parental rats HISTOPATHOLOGY / ORGAN WEIGHTSThe tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.: macroscopic examination was performed
- Postmortem examinations (offspring):
- SACRIFICE - The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at ) on lactation day 21 days of age. - These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows: GROSS NECROPSY - Gross necropsy consisted of external and internal examinations ,sex and body weight HISTOPATHOLOGY / ORGAN WEIGTHS The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.
- Statistics:
- No data available
- Reproductive indices:
- No data available
- Offspring viability indices:
- No data available
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Hair loss appeared to be more prominent in 250mg/kg dose group F0 females than in other groups
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Description (incidence):
- There were no chemical-related deaths during the study
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Body weights of parental rats were lower in some of the 100mg/kg and 250 mg/kg dose groups at some points in the study, but the difference with controls was generally <10%.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Changes in food consumption tended to parallel the changes in body weight and were generally <10% different than controls.
- 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:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects on reproduction or fertility were observed at any of the dose levels evaluated in this study.
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 250 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- food consumption and compound intake
- reproductive performance
- Remarks on result:
- other: No treatment-related effects on reproduction or fertility were observed at any of the dose levels
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Hair loss appeared to be more prominent in 250mg/kg dose group F1 females than in other groups
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- reduced male and female F1 pup weights in the 250mg/kg dose group on lactation days 14 and 21
- Food consumption and compound intake (if feeding study):
- not specified
- 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
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- F1 males showed mottled kidneys with incidences of 0/23, 2/23 (9%), 6/23 (26%), and 8/23 (35%) of the males (control and increasing dose groups). Microscopy revealed inflammation, hyaline droplet and granular cast formation, and regeneration of tubules.
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not specified
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- clinical signs
- body weight and weight gain
- organ weights and organ / body weight ratios
- Remarks on result:
- other: overall no developmental toxic effects observed
Target system / organ toxicity (F1)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- mortality observed, treatment-related
- Description (incidence and severity):
- Decreased F2 pup viability in the 50mg/kg and 250mg/kg dose groups on postnatal day 4
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Reduced male and female F2 pup weights in the 250mg/kg bw dose group on lactation days 14 and 21
- Food consumption and compound intake (if feeding study):
- not specified
- 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
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F2)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not specified
Effect levels (F2)
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- mortality
- body weight and weight gain
- Remarks on result:
- other: overall no developmental toxic effects observed
Target system / organ toxicity (F2)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Any other information on results incl. tables
Body Weight (g) of Rats on Lactation Day 21 in a 2-Generation Reproductive Study
Doses (mg/kg/day) | 0 | 25 | 100 | 250 |
F1 male | 46.2±6.50a | 46.8 ±5.06 | 45.7 ±4.53 | 40.1 ±4.22b |
F1 female | 44.1 ±4.64 | 44.6 ±4.44 | 44.2 ±4.51 | 39 1± 4.60b |
F2 males | 50.4 ±4.31 | 49.4 ±6.07 | 47.9 ±4.02 | 44.5± 3.93b |
F2 Female | 47.3± 4.52 | 47.6 ± 5.35 | 44.1 ±7.50 | 42.3± 3.23b |
aMean±standard deviation.bp<0.01.
Applicant's summary and conclusion
- Conclusions:
- No Observed Effect Level (NOEL) for reproductive toxicity was considered to be 250mg/kg/day, and NOAEL dose-level of 100 mg/kg/day was considered to be for developmental toxicity. When male and female Sprague Dawley rats were treated with test material orally.
- Executive summary:
A two-generation reproductive study of test material was performed in male and female Sprague-Dawley rats. Test material in dose concentration 0, 500, 2,000, or 5,000 ppm ( 0, 25, 100, or 250 mg /kg/day) were fed diets.The F0 parental generation consistedof 28 males and 28 females pergroup which were administered treated or control diet for at least 80 days prior to mating. Twenty-eight male and 28female offspring per group from the F1 generation were selected randomly to become the parents of the F2generation. These animals were treated for at least 93 days prior to mating. For bothparental groups, treatment wascontinued through gestation and lactation.After weaning, 10 pups/sex/groups were subjected to gross necropsy. F0 females were killed after the selection of F1 parents. F1 females were sacrificed after weaning of their litters. The parameters were used to assess toxicity were twicedaily observations for deaths and clinical signs, body weight, and food consumption (not measured during the mating periods). Additionally, gross necropsy and histological examination of the ovaries, prostate, seminal vesicles, testes with epididymides, uterus, vagina, and all gross lesions were conducted in all parental rats and 10 weanlings/sex/group in the control and 250mg/kg/daydose groups. Parameters used to assess developmental toxicity in the F1 and F2 litters included number of live and stillborn pups, external anomalies, sex and body weight grouped by sex on lactation days 0, 4, 7, and 14, sex and individual body weights (only group weights reported) on lactation day 21, viability, and behavioral abnormalities at least twice daily during lactation.
There were no chemical-related deaths during the study. Hair loss appeared to be more prominent in 250mg/kg /day dose group F0 and F1 females than in other groups. Body weights of parental rats were lower in some of the 100 mg/kg /day and 250mg/kg /day dose groups at some points in the study, but the difference with controls was generally <10%. Changes in food consumption tended to parallel the changes in body weight and were generally <10% different than controls. F1 males showed mottled kidneys with incidences of 0/23, 2/23 (9%), 6/23 (26%), and 8/23 (35%) of the males (control and increasing dose groups). Microscopy revealed inflammation, hyaline droplet and granular cast formation, and regeneration of tubules. No explicit information was provided in the review regarding the other organs examined.Neonatal toxicity as evidences by reduced pup sizes in both generations was noted for males and females250mg/kg /day groups on postnatal day 4 and reduced male and female F1 and F2 pup weights in the 250mg/kg /day dose group on lactation days 14 and 21.No treatment-related effects on reproduction or fertility were observed at any of the dose levels evaluated in this study. HenceNo Observed Effect Level (NOEL) for reproductive toxicity was considered to be 250mg/kg/day, and NOAEL dose-level of 100 mg/kg/day was considered to be for developmental toxicity.When male and femaleSprague Dawley rats were treated withtest materialorally.
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