Phenylacetic acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

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 peer reviewed journal

Data source

Reference

Reference Type:

publication

Title:

AN IMMUNOTOXICITY ASSESSMENT OF FOODFLAVOURING INGREDIENTS

Author:

C. L. GAWORSKI,

Year:

1994

Bibliographic source:

Fd Chem. Toxic. , 1994

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Immunotoxicity of test chemical was assessed in CD1 mice.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phenylacetic acid

EC Number:

203-148-6

EC Name:

Phenylacetic acid

Cas Number:

103-82-2

Molecular formula:

C8H8O2

IUPAC Name:

phenylacetic acid

Details on test material:

- Name of test material (as cited in study report): phenylacetic acid
- Substance type: Organic
- Physical state: Solid

Test animals

Species:

mouse

Strain:

CD-1

Sex:

female

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: 6-8 wk of age
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: group housed in polypropylene cages with hardwood chip bedding
- Diet (e.g. ad libitum): Certified Purina Rodent Chow 5002 Ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26°C
- Humidity (%): 10-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12-hr light/dark cycle.

IN-LIFE DATES: From: To: no data

Administration / exposure

Route of administration:

other: intragastrically

Vehicle:

other: 1% methyl cellulose

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
Test chemical was diluted with 1% methyl cellulose

Amount of vehicle : 10ml/kg

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

5 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 250, 500 or 1000 mg/kg bw
Basis:

No. of animals per sex per dose:

Total :120
0 mg/kg bw:30 females
250 mg/kg bw:30 females
500 mg/kg bw:30 females
1000 mg/kg bw:30 females

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
-observed twice each day

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
No data

FOOD EFFICIENCY: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data

OTHER:
Body weights of the mice used in the PFC assay were measured at the time of dosing initiation, exposure day 5, and at autopsy. Spleen and thymus weights were measured following removal from all animals in
the PFC assay, with organ/body weight ratios calculated using individual body weights measured at the
time of autopsy. PFC assay was carried out

Sacrifice and pathology:

GROSS PATHOLOGY: No data
HISTOPATHOLOGY: No data

Statistics:

Dunnett's test and chi-square analysis were used to evaluate mean survival time and mortality data in the host resistance assay. For continuous response data, analysis of variance (two tailed) and appropriate post-hoe comparisons using Dunnett's test were performed on natural logarithmic or Iog it transformed PFC data, For the positive control group, post-hoc comparisons were made to the naive control group using a Student's t-test. Individual groups of data were evaluated for outliers prior to statistical analysis (Dixon, 1953)

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Description (incidence):

Mortalities were observed at all the dose concentration

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

not examined

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not specified

Effect levels

Dose descriptor:

NOEL

Effect level:

1 000 other: mg/kg bw

Based on:

test mat.

Sex:

female

Basis for effect level:

other: no effect observed on body weight, mortality observed in all dose group, no plaque forming cells were observed

Remarks on result:

other: No toxic effects were observed

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The No observed effect level (NOEL) of test chemical in CD1 rats in a 5-day study was observed at a dose concentration of 1000 mg/kg bw.

Executive summary:

Immunotoxicity of test chemical was assessed in CD1 mice. Female CD1 mice were administered intragastrically with test chemical at a dose concentration of 0, 250 or 500, 1000mg/kg bw on a daily basis for 5 days. A host resistance assay and plaque-forming cell (PFC) response to sheep erythrocytes were carried out. The results indicated that the test chemical did not modulate the cell-mediated or humoral immune response. no cheange in body weight was observed .Hence No observed effect level (NOEL) for test chemical was considered to be 1000 mg/kg bw,.