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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 July 2004 - 17 Sept 2004
Reliability:
1 (reliable without restriction)
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2,5-xylenol (CAS 95-87-4), 3,4-xylenol (CAS 95-65-8), 2,4-xylenol (CAS 105-67-9), 3,5-xylenol (CAS 108-68-9), 2,3-xylenol (CAS 526-75-0), 2,6-xylenol (CAS 576-26-1). Test substancec was a mixture of xylenol isomers.
- Analytical purity: 99.74%
- Isomers composition: 2,5-xylenol (CAS 95-87-4): 16.4 mole %, 3,4-xylenol (CAS 95-65-8): 16.9 mole %, 2,4-xylenol (CAS 105-67-9): 22.7 mole %, 3,5-xylenol (CAS 108-68-9): 11.1 mole %, 2,3-xylenol (CAS 526-75-0): 18.2 mole %, 2,6-xylenol (CAS 576-26-1): 14.7 mole %.
- Lot/batch No.: 20NOV2003

Test animals

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test substance was prepared as a solution in the vehicle and administered orally by gavage.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
GC/FID analysis of dosing preparation concentration, stability and homogeneity.
Duration of treatment / exposure:
28 days for males and 54 days for females.
Frequency of treatment:
Daily administration beginning 14 days prior to cohabitation and continuing until the day before sacrifice.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 30, 100 and 245 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
10 rats per sex per group
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least 2/day

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: 2/day

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

Observations were performed for viability, clinical signs of toxicity, food consumption, body weight gain, functional observational battery and motor activity, hematology, clinical chemistry, developmental toxicity and reproductive performance, gross and microscopic post-mortem examination.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Statistics:
Body weight, weight gains and reproductive end points analysed by ANOVA and Dunnett's. Reproductive data analysed by Fisher's exact test.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
Relative weights of kidney, liver and ovaries were increased in the high dose group.

Effect levels

Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: Due to clinical observations (urine-stained fur, increased kidney, liver and ovarian relative weight).

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

All rats survived the treatment. In males, urine stained fur was observed at the 245 mg/kg/day level. Body weight gain and food consumption were unaffected by treatment. Mating frequency was reduced at the 245 mg/kg/day level. Neurotoxicity was not observed during the study and there were no treatment related effects observed at gross necropsy or histopathologically. Urine staining of the fur was observed in females at the 245 mg/kg/day level. F1 animals showed no treatment related clinical or necropsy signs. Haematology and clinical pathology parameters were unaffected.

Reproductive indices are discussed under section 7.8.1.

Applicant's summary and conclusion

Conclusions:
The test substance mixed xylenol isomers was administered to rats by oral gavage at 0, 30, 100 and 245 mg/kg/day. The general toxicological No Observable Adverse Effect Level was shown to be 100 mg/kg/day.

The reproductive NOAEL is discussed under section 7.8.1.