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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

A valid subchronic study is available sufficient for evaluation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically acceptable and well documented
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Principles of method if other than guideline:
Dibenzyl ether (FEMA No. 2371, CAS No. 103-50-4) was given in the diet to rats at a rate of 62, 196 or 620 mg/kg/day for 91 consecutive days. Body weights and food consumption were measured weekly; haematological, clinical chemistry and urinalysis values were obtained at wk 6 and 12. Gross and microscopic pathological changes were examined and organ weights recorded.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
other: CD-Cal:(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
No data
Route of administration:
oral: feed
Vehicle:
other: diet
Details on oral exposure:
No data
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
91 days
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
62 , 196 or 620 mg/kg/day
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
196 mg/Kg/day
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
620 mg/Kg/day
Basis:
nominal in diet
No. of animals per sex per dose:
dose of dibenzylether:
0 mg/kg/day: 24 males and 24 females
62 mg/kg bw: 16 males and 16 females
196 mg/kg bw: 12 males and 12 females
620 mg/kg bw: 10 males and 10 females
Control animals:
yes, concurrent vehicle
Details on study design:
No data
Positive control:
No data
Observations and examinations performed and frequency:
No data
Sacrifice and pathology:
No data
Other examinations:
No data
Statistics:
No data
Clinical signs:
no effects observed
Description (incidence and severity):
No clinical signs of toxicity were observed during the course of the study.
Mortality:
no mortality observed
Description (incidence):
There were no deaths.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No significant changes of the mean body weights were observed throughout the study.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Sporadic changes in food consumption occurred during the course of study, but were not attributable to test substance administration.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Description (incidence and severity):
There was a decrease in erythrocyte count, haemoglobin and haematocrit in mid- and high-dose females at the 6-wk interval, which appeared to be resolving at the 12-wk interval, with the exception of the haematocrit in the mid- and high-dose females and erythrocyte counts in the mid-dose females. As some of the decreases appeared to resolve during the intervening 6 wk, and since the erythrocyte count and haematocrit were significantly elevated in males and the values were within normal limits for the laboratory for this strain, these and other effects in the haemograms were considered to be transient and not toxicologically significant.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
At the 6-wk interval, serum aspartate aminotransferase (AsT) and alanine aminotransferase (AlT) were significantly increased in mid- and high-dose males and AsT was elevated in the high-dose females. These increases were no longer apparent at the 12-wk interval and the values for these groups were, in fact, slightly lower than those of the controls. The changes in liver enzymes and other changes occurring sporadicalIy throughout the groups were not considered to be toxicologically significant.
Urinalysis findings:
no effects observed
Description (incidence and severity):
Urinalyses (data not presented) were unremarkable.
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
There was a statisticalIy significant increase in absolute and relative liver weight in high-dose females at study termination. Other increases occurred sporadically throughout the groups of females in one or another of the paired organs and were not considered to be biologically significant.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No macroscopic or microscopic abnormalities were seen that could be attributed to treatment with the test substance.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No macroscopic or microscopic abnormalities were seen that could be attributed to treatment with the test substance.
Histopathological findings: neoplastic:
not examined
Other effects:
no effects observed
Details on results:
The high-dose females had increased absolute and relative liver weights; this was considered to be related to dose. Other statistically significant events that occurred sporadically within the test groups were unrelated to dose and were considered to be normal adaptive change. No toxicological or pathological effects were noted at any of the dose levels after 91 consecutive days of feeding dibenzyl ether. A no-effect level was achieved at 196 mg/kg/day
Key result
Dose descriptor:
NOAEL
Effect level:
620 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Key result
Critical effects observed:
no

No clinical signs of toxicity were observed during the course of the study; there were no deaths. No significant changes of the mean body weights were observed throughout the study for Sporadic changes in food consumption occurred during the course of study, but were not attributable to test substance administration.

There was a decrease in erythrocyte count, haemoglobin and haematocrit in mid- and high-dose females at the 6-wk interval, which appeared to be resolving at the 12-wk interval, with the exception of the haematocrit in the mid- and high-dose females and erythrocyte counts in the mid-dose females. As some of the decreases appeared to resolve during the intervening 6 wk, and since the erythrocyte count and haematocrit were significantly elevated in males and the values were within normal limits for the laboratory for this strain, these and other effects in the haemograms were considered to be transient and not toxicologically significant.

At the 6-wk interval, serum aspartate aminotransferase (AsT) and alanine aminotransferase (AlT) were significantly increased in mid- and high-dose males and AsT was elevated in the high-dose females. These increases were no longer apparent at the 12-wk interval and the values for these groups were, in fact, slightly lower than those of the controls. The changes in liver enzymes and other changes occurring sporadicalIy throughout the groups were not considered to be toxicologically significant.

Urinalyses (data not presented) were unremarkable.

There was a statisticalIy significant increase in absolute and relative liver weight in high-dose females at study termination. Other increases occurred sporadically throughout the groups of females in one or another of the paired organs and were not considered to be biologically significant.

No macroscopic or microscopic abnormalities were seen that could be attributed to treatment with the test substance.

Executive summary:

Dibenzyl ether was given in the diet to rats at a rate of 62, 196 or 620 mg/kg/day for 91 consecutive days. Body weights and food consumption were measured weekly; haematological, clinical chemistry and urinalysis values were obtained at wk 6 and 12. Gross and microscopic pathological changes were observed and organ weights recorded. The high-dose females had increased absolute and relative liver weights; this was considered to be related to dose. Other statistically significant events that occurred sporadically within the test groups were unrelated to dose and were considered to be normal adaptive change. No toxicological or pathological effects were noted at any of the dose levels after 91 consecutive days of feeding dibenzyl ether. A no-effect level was achieved at 196 mg/kg bw/day. The NOAEL was 620 mg/kg bw/day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
620 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Scientifically acceptable and sufficiend documented for evaluation.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Dibenzyl ether was given in the diet to rats at a rate of 62, 196 or 620 mg/kg/day for 91 consecutive days. Body weights and food consumption were measured weekly; haematological, clinical chemistry and urinalysis values were obtained at wk 6 and 12. Gross and microscopic pathological changes were examined and organ weights recorded.

The high-dose females had increased absolute and relative liver weights; this was considered to be related to dose. Other statistically significant events that occurred sporadically within the test groups were unrelated to dose and were considered to be normal adaptive change. No toxicological or pathological effects were noted at any of the dose levels after 91 consecutive days of feeding dibenzyl ether. A no-effect level was achieved at

196 mg/kg bw/day. The NOAEL was 620 mg/kg bw/day.


Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver

Justification for classification or non-classification

In the highest applied dose (620 mg/kg bw/day) the only treatment related effects were absolute and relative liver weights. Other effects were unrelated to dose and were considered to be normal adaptive effects.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.