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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
Reference
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

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.

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).

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).