Registration Dossier

Administrative data

Endpoint:
immunotoxicity: acute oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No data on analytical purity of test substance otherwise sufficiently well reported to judge the results reliable with restrictions for use in risk assessment.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Comparative immunosuppression of various glycol ethers orally administered to Fischer 344 rats.
Author:
Smialowicz RJ, Williams WC, Riddle, MM et al
Year:
1992
Bibliographic source:
Fundam Appl Toxicol, 18(4), 621-7
Reference Type:
publication
Title:
The immunotoxicity of 2-methoxyethanol and its metabolites.
Author:
Smialowicz RJ
Year:
1996
Bibliographic source:
Occup Hyg, vol 2, p269-74

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Rats orally administered substance in two doses over a 2 day period then the humoral immune system functionality assessed with a T-dependent antigen response assay
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
-Source:Aldrich Chemical Company, Milwaukee, Mo
- Analytical purity:no data

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
-Source: Source: Charles River Laboratory, Raleigh, NC
-Age at study initiation: 8-10 weeks
-Housing: 3 per polycarbonate cage, heat treated pine shavings bedding.
-Diet: Purina Lab Chow, Purina Mills, ad libitum
-Water: ad libitum

ENVIRONMENTAL CONDITIONS
-Temperature: 22C
-Humidity: 50-60%
-Photoperiod: 12hrs dark/12hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: distilled water
Details on exposure:
Preparation of dosing solution: no data
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
dosing volume 2.5ml/kg
Duration of treatment / exposure:
2 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
50, 100, 200, 400mg/kg per day
Basis:

No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle

Examinations

Humoral immunity examinations:
Method: Rats were immunized with a single intravenous injection of trinitrophenyl-Lipopolysaccharide (TNP-LPS) 2-4hrs prior to substance exposure. 3 days after final exposure, a splenic antibody plaque forming assay (PFC) using SRBC was carried out using the method of Smialowicz (Toxicology 44, 271, 1987).
Dose groups: See above
Number of animals: See above.
Statistics:
Results expressed as mean and standard deviation. Data analysed by one way analysis of variance with post analysis using Dunnett’s multiple comparison t-test or the Student-Newman-Kuels multiple range test as required. Significance level set at p<0.05.

Results and discussion

Results of examinations

Clinical signs:
not examined
Mortality:
not examined
Body weight and weight changes:
not examined
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
Gross pathological findings:
not examined
Details on results:
Humoral immunity examinations: When expressed as cells/spleen, the 400mg/kg dose group showed a siginficant reduction but this was not evident in the 800mg/kg dose group, therefore the change in the 400mg/kg group was not regarded as biologically significant. No significant effects were seen in any of the other parameters assessed.

Specific immunotoxic examinations

Cell viabilities:
not examined
Humoral immunity examinations:
no effects observed
Specific cell-mediated immunity:
not examined
Non-specific cell-mediated immunity:
not examined
Other functional activity assays:
not examined
Other findings:
not examined

Effect levels

Dose descriptor:
NOAEL
Effect level:
> 800 mg/kg bw/day
Sex:
male
Basis for effect level:
other: Humoral immunity markers

Applicant's summary and conclusion

Conclusions:
Substance has no significant effects on humoral immunity.
Executive summary:

Treatment of rats acutely with 2 -(2 -methoxyethoxy)ethanol causes no significant suppression of the antibody response to TNP-LPS at doses up to 800mg/kg.