Registration Dossier
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EC number: 203-149-1 | CAS number: 103-83-3
Endpoint summary
Administrative data
Description of key information
There are subacute oral toxicity studies available in rats dosed with N,N-Dimethylbenzylamine up to 400 mg/kg bw/day by gavage for 28 days resulting in a NOAEL of 150 mg/kg bw/day.
A study according to OECD TG 408 (rat, oral) and GLP is planned after the approval by ECHA.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: guideline test and GLP
- Reason / purpose:
- reference to same study
- Qualifier:
- according to
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
- GLP compliance:
- yes
- Species:
- rat
- Strain:
- other: Crl:CD(SD)BR
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: males 158.5-184.5 g femalew:116.1-153.9 g
- Housing: 5
- Diet ad libitum
- Water ad libitum
- Acclimation period: 13 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- The test article was administered daily by gavage for 28 days
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- the achieved concentration was measured during week 1 and week 2 the analytical procedure HUK624/1-01F
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- once daily
- Remarks:
- Doses / Concentrations:
0, 6, 30, 150 mg/kg bw/day
Basis:
actual ingested - No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- according to the respective OECD guideline
- Positive control:
- no
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily , full examination weekly
BODY WEIGHT: Yes
- Time schedule for examinations: once weekly
FOOD CONSUMPTION weekly:
WATER CONSUMPTION by visual appraisal:
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: week 4
- Anaesthetic used for blood collection: Yes (identity) / No / No data
- Animals fasted: Yes
- Parameters
hemoglobin conc., MCV,RBC, MCH, MCHC, PCV, WBC, platlet count
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: week 4
- Animals fasted: Yes
- Parameters
alkaline phosphatase, GOT/AST, GPT/ALT, blood urea, BUN, Cholesterol, creatininem glucose, total bilirubin, triglyceride,
albumin, albumin/globulin ratio,
total protein, Ca, K, Na, inorganic phosphorus
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Organ weights
adrenals liver kidneys testes
left and right organs were weighed separately
HISTOPATHOLOGY: Yes
tissues from control and high dose animals initially
tissue preservation
adremals, aorta, brain (medullary and cerebellar and cortical sections),
colon (duodenum, caecum, jejunum rectum), kidneys, liver, lungs, lymph nodes (mandibular and nesenteric) ,
eyes and optic nerve, oesophageousm pancreasm prostatem salivary glands, seminal vesicles, spinal cord, stomach,
thymus, trachea, uterus including cervix, ovaries, pituitary gland, femur with bone marrow, mammary gland, sciatic nerve,
skin, spleen, testes with epididymides, thyroid with parathyroids urinary bladder - Other examinations:
- no data
- Statistics:
- anlysis of variance, t-test, Kruskal-Wallis test, Wilcoxon test
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
there were no clinical observations that were considered to be related to treatment
During week 4 1 control male died and in the intermediate dose 1 female
Both death were considered to result vrom blood sampling/anesthetic
BODY WEIGHT AND WEIGHT GAIN
The body weight gain of male and female rats was considered not to have been affected by treatment
HAEMATOLOGY and CLINICAL CHEMISTRY
The measured haematological and clinical chemistry parameters were considered to have remained unaffected by treatment
ORGAN WEIGHTS
Organ weights in test animals were in general comparable to organ weights of control animals
the absolute and relative testis weights for high dose group males were slightly higher han those of the controls.
However there was no histopathological correlate
Testis weights for the low and intermediate dose group males were similiar to those of the controls
GROSS PATHOLOGY and HISTOPATHOLOGY: NON-NEOPLASTIC
there were no histopathological findings of any unusual nature or incidence suggestive of target organ toxicity - Dose descriptor:
- NOAEL
- Effect level:
- ca. 150 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: There were no major differences between control and treated rats. The high dose group males had slightly higher testis weights than the controls. However there was no histopathological correlate
- Critical effects observed:
- not specified
- Executive summary:
In an test according to OECD TG 407 and GLP groups of male and female Crl:CD(SD)BR rats received N,N-Dimethylbenzylamine in corn oil by daily oral gavage at nominal dose levels of 6, 30 or 150 mg/kg bw/day. A further group of the same size received corn oil alone and served as control. There were no major differences between control and treated rats. The high dose group males had slightly higher testis weights than the controls. However there was no histopathological correlate. Therefore this finding was considered not to be of toxicological relvance. The NOAEL was determined to be 150 mg/kg bw/day (BG Chemie 1988).
Reference
The data were processed, where appropriate, to give group mean values and standard deviations. The nature of the data was considered to be such that statistical analysis would not have provided additional information.
Endpoint conclusion
- Dose descriptor:
- NOAEL
- 150 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
Additional information
ORAL ADMINISTRATION
There is no sub-chronic study available. In accordance with section 1 of REACH Annex XI, a sub-chronic repeated dose toxicity study is not required.
There are 2 sub-acute oral studies available which are performed according the respective guideline and in which the test substance
was applied by gavage to male and female rats in dosages of 0, 6, 30, 150, 200 mg/kg bw/day (BG Chemie 1988, 1990) or 0, 50, 100, 200, 400 mg/kg bw/day (MHLW 1997), respectively. In addition, rats of the control group and rats treated with 200 and 400 mg/kg bw/day were observed after termination of treatment for further 2 weeks (recovery group, MHLW 1997).
Mortalities of both males and females receiving 400 mg/kg were observed from week 2. Miosis and salivation was observed in those rats receiving 200 and 400 mg/kg bw/day. The 150 mg/kg bw/day males had slightly higher testis weights than the controls. However, there was no histopathological correlate. In male and female animals dosed with 100 mg/kg bw/day miosis was the only observed finding . There were no differences between controls and male and female rats dosed with 50, 30 or 6 mg/kg bw/day. Thus, the overall NOAEL is considered to be 150 mg/kg bw/day.
A study according to OECD TG 408 (rat, oral) and GLP is planned after the approval by ECHA.
DERMAL APPLICATION
There are no data available
INHALATION EXPOSURE
There are no valid studies available
Justification for classification or non-classification
Based on the available data, no classification is required according to the classification criteria 67/548/EWG and EU Regulation 1272/2008 (CLP/GHS).
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