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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Endpoint:
repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
429-220-9
EC Name:
-
Cas Number:
132584-17-9
Molecular formula:
C17 H18 O4
IUPAC Name:
ethyl 2-hydroxy-2-(4-phenoxyphenyl)propanoate
Test material form:
liquid
Specific details on test material used for the study:
Purity: 73.5%
Batch: IN-JG303-7

Test animals

Species:
rat
Strain:
other: Crl:CD (SD)IGS BR
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Suspension in 0.5% methyl cellulose
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
28 days
Frequency of treatment:
7 days/week
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
15 mg/kg bw/day (nominal)
Dose / conc.:
150 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
No. of animals per sex per dose:
5/sex/dose level
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
All rats were evaluated for clinical observations, body weights, and food consumption throughout the study. Full functional observational battery (FOB) and motor activity (MA) tests were conducted prior to study start (baseline) and during week 4. An abbreviated FOB was conducted at weekly intervals during weeks 1-3. Prior to terminal sacrifice, blood was taken from each rat and evaluated for hematology and clinical chemistry parameters.
Sacrifice and pathology:
All rats were sacrificed on test day 29 and necropsied. All collected tissues from all rats in the 0 and 500 mg/kg/day dose groups were processed and received a full histological examination. Liver, kidney, and lungs were examined from rats in the 15 and 150 mg/kg/day dose groups.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Clinical signs of wet chin, wet perineum, low arousal, and ptosis were observed at 500 mg/kg/day throughout the study.
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Body weight gains were decreased in the 500 mg/kg/day male rats.
Food efficiency:
effects observed, treatment-related
Description (incidence and severity):
Food efficiency were decreased in the 500 mg/kg/day male rats.
Behaviour (functional findings):
no effects observed
Description (incidence and severity):
There was no evidence that the test substance produced a neurotoxic effect. Forelimb grip strength, hindlimb grip strength, foot splay, and motor activity were unaffected by the test substance. Clinical signs of neurotoxicity were not observed in the study.
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
The mean kidney weight relative to body weight was increased 73% in males and 64% in females in the 500 mg/kg/day groups. These increases were test substance-related and correlated with biologically adverse gross and microscopic findings.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
The kidneys of the 500 mg/kg/day male and female rats were noted as large, large and pale, or discolored. .
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
A spectrum of lesions occurred in the renal cortex and medulla of both male and female rats dosed at 500 mg/kg/day. Affected kidneys were characterized primarily by dilatation of tubules, regeneration of affected tubular epithelial cells, and the presence of hyaline casts within the collecting ducts
Details on results:
Clinical observations:
There were no deaths, but at 500 mg/kg, clinical signs in
both both males and females included wet chin, wet perineum,
low arousal and ptosis.

Laboratory findings:
There were minor changes in blood chemistry parameters at
500 mg/kg/day, but were not thought to be toxicologically
significant. Some of the observed effects were considered
to be associated with adaptive changes to the kidneys.


There were no adverse effects in other goups.

Effects in organs:
Effects were noted in the kidneys at 500 mg/kg/day,
including lesions to the renal cortex and medulla in males
and females. There was also an increase in the mean kidney
weights at 500 mg/kg/day, with an increase in size

observed, together with discolouration.

Effect levels

Dose descriptor:
NOAEL
Effect level:
150 mg/kg bw/day (nominal)
Sex:
male/female

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study, the NOEL was 150 mg/kg in both males and females based on biochemical and pathological evidence of toxicity in the 500 mg/kg/day males and females.